{"@context":"https://w3id.org/ro/crate/1.1/context","@type":"Dataset","id":"342e6c9b-631f-4021-99a2-d4eda568ae58","name":"Research Synthesis: Sleep Architecture Deep Sleep — full paper","doi":"10.17605/OSF.IO/SGDU2","doi_status":"minted","osf_url":"https://osf.io/sgdu2/","dw_chain_url":"https://provenance.researka.org/artifacts/claim_7a1c20558edd4d8c/chain","content_hash":"sha256:b373e675d3dbd4df0ce287f06dc7ca3efe4e0028010ac6cc38a2f2650a86106d","provenance_passport":{"publication_id":"342e6c9b-631f-4021-99a2-d4eda568ae58","submission_id":"d574338c-d2ca-4dc2-a3f6-0f21810e0f30","artifact_type":"research_paper","decision":"accept","content_hash":"sha256:b373e675d3dbd4df0ce287f06dc7ca3efe4e0028010ac6cc38a2f2650a86106d","persistent_identifiers":{"doi":"10.17605/OSF.IO/SGDU2","osf_url":"https://osf.io/sgdu2/","orcid":null,"ror_id":null,"raid_id":null},"persistent_identifier_status":{"doi":"supplied","osf_url":"supplied","orcid":"not_supplied","ror_id":"not_supplied","raid_id":"not_supplied"},"institution":{"name":null,"ror_id":null,"status":"not_supplied"},"integrity":null,"provenance":{"dw_artifact_id":"claim_7a1c20558edd4d8c","dw_chain_url":"https://provenance.researka.org/artifacts/claim_7a1c20558edd4d8c/chain"},"timeline":["submission_intake","autonomous_review","autonomous_editorial_decision","autonomous_publish"]},"publication":{"id":"342e6c9b-631f-4021-99a2-d4eda568ae58","object_type":"publication","parent_object_id":"d574338c-d2ca-4dc2-a3f6-0f21810e0f30","title":"Research Synthesis: Sleep Architecture Deep Sleep — full paper","body_markdown":"# Research Synthesis: Sleep Architecture Deep Sleep — full paper\n\n## Abstract\n\nThis synthesis tests the thesis that evidence for Sleep architecture deep sleep is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation.\n\nSleep architecture, particularly the proportion of deep slow-wave sleep (SWS), is increasingly recognized as a potential marker of neurological and cardiometabolic health, yet its independent causal role remains poorly defined.\n\nThis synthesis applied structured evidence mapping to 28 reference papers, classifying studies by outcome domain (e.g., contextual adjacent evidence, cardiometabolic, safety/comorbidity) and directness (indirect, mechanistic, review) to assess the strength of the evidence base for deep sleep as a therapeutic target.\n\nThe search identified no direct human randomized controlled trial evidence linking deep sleep modification to hard clinical endpoints, with all 28 sources coded as indirect, mechanistic, or review evidence.\n\nThe evidence profile indicates that the evidence supports that deep sleep is a biologically plausible and modifiable marker associated with neurological, cardiometabolic, and musculoskeletal outcomes, but the current human evidence base is overwhelmingly observational and indirect.\n\nThe therapeutic potential of enhancing deep sleep remains promising but unproven, as direct RCT evidence linking deep sleep augmentation to improved hard clinical endpoints is currently absent, and the boundary conditions for clinical benefit remain to be is consistent with.\n\n**Evidence-abstraction note.** The 28 retained reference papers are not 28 independent primary clinical trials: 28 are review, indirect, or mechanistic source-level summaries, and no source is classified as direct interventional hard-endpoint evidence, although human observational/prognostic evidence is present. Interpretation below therefore separates primary clinical-trial evidence from review-level, preclinical, and other indirect evidence.\n\n## Methods\n\n### Review type and protocol\nThis manuscript is reported as a Evidence brief. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary `methods_pack.json` and the timestamped submission directory `synthesis-sleep_architecture_deep_sleep-v06-DAILY-2026-06-02T04-31-15Z-R2`.\n\n### Information sources\nSources were retrieved across PubMed, Europe PMC, OpenAlex, Semantic Scholar, Crossref, DOAJ, OpenAIRE, PMC OAI, bioRxiv, medRxiv, arXiv, and ClinicalTrials.gov. Retrieval window: 2026-06-02.\n\n### Search strategy\nThe following topic-anchored queries were executed against the information sources listed above:\n\n- `sleep architecture deep sleep AND aging AND human`\n- `sleep architecture deep sleep AND older adults`\n- `sleep architecture deep sleep AND randomized controlled trial`\n- `deep sleep AND aging AND human`\n- `deep sleep AND older adults`\n- `deep sleep AND randomized controlled trial`\n- `slow-wave sleep AND aging AND human`\n- `slow-wave sleep AND older adults`\n- `slow-wave sleep AND randomized controlled trial`\n- `sleep architecture AND aging AND human`\n\n### Eligibility criteria\n- Sources whose primary content addresses sleep architecture deep sleep.\n- Sources with extractable quantitative or qualitative findings.\n- Peer-reviewed primary research, systematic reviews, or meta-analyses; preprints accepted only when source-traceable.\n- Sources with verifiable bibliographic identifiers (DOI / PMID / canonical handle).\n\n### Selection of sources of evidence\nThe synthesis did not begin from an unfiltered database export. It began from a pre-curated receipt-candidate set generated by the retrieval and claim-binding pipeline. Of 169 records in the receipt-candidate union, 49 were classified as source candidates and 28 were admitted as traceable synthesis sources. Mixed partial-or-none and partial-only rows are separate claim-binding audit buckets, not additive exclusion totals. No additional records were excluded after final source admission.\n\n### source admission funnel\n\n| Admission bucket | n |\n|---|---:|\n| Receipt candidate union | 169 |\n| Classified source candidates | 49 |\n| No extractable claims | 16 |\n| None-only claim binding | 16 |\n| Mixed partial-or-none claim-binding candidates | 78 |\n| Partial-only claim-binding candidates | 10 |\n| Strict high-confidence sources | 0 |\n| Admitted final sources | 28 |\n\n### Exclusion reasons\n- Non-traceable findings (claim could not be linked to source text): 0 records.\n- Wrong population / off-topic sources excluded at screening.\n- Duplicate records deduplicated by DOI / PMID before screening.\n\n### Data items\nThe following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias appraisal, and claim registry) rather than from re-parsed full text.\n\n### Risk-of-bias appraisal\nPer-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in `risk_of_bias.json`.\n\n### Synthesis approach\nEvidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, frailty, muscle function, safety and comorbidity); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.\n\n### AI-use disclosure\nSource retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified.\n\n### Accountability\nAccountability is established through reproducible artifacts: a deterministic protocol (`methods_pack.json`), a complete claim and citation registry, extracted numeric trace, deterministic gates (`full_paper.journal_surface.json`, `pre_submit_gate.json`, `artifact_consistency.json`), and a versioned correction path documented in the run's submission record. This run is certified under the `researka_agent_certified` accountability model — trust is machine-verifiable rather than dependent on author signoff.\n\n## Results\n\n**Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim.\n\n| Outcome class | Corpus slice | Strongest signal | Directness | Main limitation |\n|---|---|---|---|---|\n| Contextual Adjacent Evidence | n=20; claims=565 | no extracted directional signal in 20/20 sources | 17 indirect; 1 mechanistic; 2 review | limited corpus depth in this outcome class |\n| Cardiometabolic | n=3; claims=163 | no extracted directional signal in 3/3 sources | 3 indirect | limited corpus depth in this outcome class |\n| Safety and Comorbidity | n=3; claims=260 | no extracted directional signal in 3/3 sources | 1 indirect; 1 mechanistic; 1 review | limited corpus depth in this outcome class |\n| Frailty | n=1; claims=25 | negative signal in 1/1 sources | 1 indirect | single-source slice; hypothesis-generating |\n| Muscle Function | n=1; claims=42 | no extracted directional signal in 1/1 sources | 1 indirect | single-source slice; hypothesis-generating |\n\nThis evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate.\n\n### Contextual Adjacent Evidence Outcomes\n\n20 included sources were assigned to this outcome class. Directional coding: null=20. Directness coding: indirect=17, mechanistic=1, review=2.\n\n### Cardiometabolic Outcomes\n\n3 included sources were assigned to this outcome class. Directional coding: null=3. Directness coding: indirect=3.\n\n### Safety Comorbidity Outcomes\n\n3 included sources were assigned to this outcome class. Directional coding: null=3. Directness coding: indirect=1, mechanistic=1, review=1.\n\n### Frailty Outcomes\n\n1 included source were assigned to this outcome class. Directional coding: negative=1. Directness coding: indirect=1.\n\n### Muscle Function Outcomes\n\n1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.\n\n## Limitations\n\n**Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.\n\nThe principal limitation is evidence-role imbalance. The retained corpus contains no sources classified primarily as direct clinical evidence, 23 adjacent clinical sources, and 2 mechanistic or model-system sources, which means causal interpretation depends on how much weight is assigned to each evidence tier.\n\nA second limitation is endpoint heterogeneity. Study-level signals span no dominant outcome class, the contextual adjacent evidence, safety and comorbidity, cardiometabolic outcome classes, the frailty outcome class, and no dominant outcome class; these domains cannot be pooled narratively without losing clinically relevant differences in measurement, population, and study design.\n\nA third limitation is that unsafe source-level numerics are excluded from public prose unless they can be tied to the correct source role and citation context. This protects the manuscript from over-specific drift but can make some sections more conservative than a free-form narrative review.\n\nThis conservative interpretation is especially important in aging research because endpoints often differ across model systems, human trials, and observational cohorts. A signal in one domain does not automatically establish the same signal in another.\n\nThe study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty.\n\nThe resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, direct clinical signals, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support.\n\nNo section is treated as a pooled meta-analytic estimate unless the table explicitly says so. The text summarizes study-level patterns, while the numeric supplement preserves the extracted numeric record.\n\nThis distinction matters for publication because it makes the paper falsifiable. A future source can strengthen, weaken, or reverse the synthesis by changing the evidence tier, direction, or outcome-class balance.\n\n## Conclusion\n\nFor sleep architecture deep sleep, the final interpretation is deliberately tiered: the retained clinical and adjacent evidence profile defines a bounded geroscience rationale, but the corpus does not support treating mechanistic target engagement, intermediate biomarkers, and patient-relevant outcomes as interchangeable evidence. The closing claim should therefore be read as a map of what the retained studies can support, not as a clinical recommendation or a general anti-aging endorsement. Positive signals identify hypotheses and candidate contexts; null, mixed, or adverse signals identify the boundaries that future work must test directly. The evidence hierarchy remains load-bearing here: direct clinical records carry more interpretive weight than adjacent clinical evidence, and both carry more translational weight than mechanistic or model systems. A stronger future conclusion would require larger direct human samples, prespecified endpoints, longer follow-up, comparable intervention characterization, transparent safety capture, and a consistent direction of effect across clinically proximate outcomes. Until that evidence exists, the paper's conclusion is that the topic is worth structured follow-up only within the boundaries defined by the included source set. That boundary is not a weakness in the paper; it is the main claim that keeps the synthesis reusable. Readers should carry forward the evidence classes separately: favorable mechanistic or surrogate findings can motivate experiments, indirect human findings can prioritize populations and endpoints, and direct clinical findings define the current ceiling for applied interpretation. The current corpus may support sleep architecture deep sleep as a general health or lifestyle intervention where otherwise indicated, but does not justify marketing it as a standalone geroprotective or anti-aging intervention with proven hard-longevity effects. Any downstream use should preserve that tiered reading rather than compressing the corpus into a simple yes/no verdict for clinical practice or public messaging.\n\n## What This Synthesis Adds\n\nThis synthesis maps 28 included sources on Sleep architecture deep sleep across 5 outcome classes and 196 cross-study disagreements. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit.\n\nAcross 28 curated reference papers, the evidence base for Sleep architecture deep sleep shows a context-dependent profile. Negative signals appear in: frailty. Null findings dominate: contextual other, safety comorbidity. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Sleep architecture deep sleep anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established.\n\nThe strongest unresolved contrast is the agreement between Mueller 2024 and Carmiol-Rodriguez 2024 on contextual adjacent evidence (severity 1/5), which defines the boundary condition future studies must test rather than smooth over.\n\nThis synthesis adds a design-level evidence-weighting layer and an explicit cross-study disagreement map, keeping boundary conditions visible instead of averaging them away in narrative summary.\n\n### Boundary-Condition Matrix\n\n| Outcome class | Direct sources | Indirect / mechanism sources | Direction profile | Interpretation boundary |\n|---|---:|---:|---|---|\n| cardiometabolic | 0 | 3 | null | direct clinical gap |\n| frailty | 0 | 1 | negative | direct clinical gap |\n| muscle function | 0 | 1 | null | direct clinical gap |\n| contextual adjacent evidence | 0 | 20 | null | direct clinical gap |\n| safety and comorbidity | 0 | 3 | null | direct clinical gap |\n\n### Evidence-Gap Priority\n\n| Priority | Gap | Rationale |\n|---|---|---|\n| P1 | cardiometabolic: direct clinical gap | 0 direct and 3 indirect sources; direction profile: null |\n| P2 | frailty: direct clinical gap | 0 direct and 1 indirect source; direction profile: negative |\n| P3 | muscle function: direct clinical gap | 0 direct and 1 indirect source; direction profile: null |\n| P4 | contextual adjacent evidence: direct clinical gap | 0 direct and 20 indirect sources; direction profile: null |\n| P5 | safety and comorbidity: direct clinical gap | 0 direct and 3 indirect sources; direction profile: null |\n\n### Next-Study Design Recommendation\n\nThe next high-yield study for Sleep architecture deep sleep should target the **cardiometabolic** evidence gap, pre-register the primary endpoint, separate clinical from mechanistic endpoints, preserve safety and adherence capture, and include an analysis plan that can falsify the current boundary-condition claim rather than only confirming a favorable direction. Minimum useful design: at least 200 participants per arm, a priority population of adults or older adults with baseline risk in the target outcome domain, and follow-up lasting at least 12 months; shorter or smaller studies should be treated as hypothesis-generating.\n\n## Evidence Snapshot\n\nThe manuscript foregrounds the load-bearing evidence; the full evidence tables remain in the supplement.\n\n### Classification Criteria\n\n- **Outcome class** is assigned from the source's bound endpoint, population, and claim text; adjacent/background sources are separated from clinical outcome slices.\n- **Directness** is coded as direct only when the source tests the topic against a clinically proximate outcome in the relevant population; indirect human, review-level, and mechanistic sources are weighted separately.\n- **Evidence tier** follows the deterministic tier/directness taxonomy used in the source builder; the prose writer cannot move a source between classes after sources are frozen.\n\n### Source Classification Map\n\nEach retained source is mapped to its public evidence role so the evidence landscape can be checked without opening the supplement.\n\n- Effect of daridorexant on sleep architecture in patients with chronic insomnia disorder: a pooled post hoc analysis of two randomized phase 3 clinical studies: outcome=safety comorbidity; directness=review; tier=B2; direction=null; claims=167.\n- Effects of daridorexant on sleep architecture in Japanese patients with insomnia disorder: analysis of a phase II randomized controlled trial: outcome=contextual adjacent evidence; directness=review; tier=B2; direction=null; claims=138.\n- Effect of chronic benzodiazepine and benzodiazepine receptor agonist use on sleep architecture and brain oscillations in older adults with chronic insomnia: outcome=safety comorbidity; directness=indirect; tier=B2; direction=null; claims=67.\n- Sleep architecture and quality of life in comorbid OSA and depression: cross-sectional analysis of the Sydney sleep biobank: outcome=cardiometabolic; directness=indirect; tier=B2; direction=null; claims=63.\n- Tai Chi exercise improves sleep quality in older adults with mild insomnia by enhancing slow-wave activity during deep sleep: a 12-week randomized controlled trial: outcome=contextual adjacent evidence; directness=review; tier=B2; direction=null; claims=57.\n- Associations between body composition, hydration status, and sleep architecture in obstructive sleep apnea: outcome=cardiometabolic; directness=indirect; tier=B2; direction=null; claims=55.\n- A longitudinal assessment of sleep architecture in children and adolescents with craniopharyngioma: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=53.\n- The impact of breaking up prolonged sitting with physical activity during simulated dayshifts and nightshifts on sleep architecture: a randomised controlled trial: outcome=cardiometabolic; directness=indirect; tier=B2; direction=null; claims=45.\n- Changes in sleep architecture during recurrent cycles of sleep restriction: a comparison between stable and variable short sleep schedules: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=42.\n- Deep sleep slow wave–spindle coupling is selectively linked to plasma amyloid-β levels in older adults in clinical trials: outcome=muscle function; directness=indirect; tier=B2; direction=null; claims=42.\n- Sleep architecture and dementia risk in adults: an analysis of 5 cohorts from the Sleep and Dementia Consortium: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=37.\n- Profiling the sleep architecture of ageing adults using a seven‐state continuous‐time Markov model: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=35.\n- Sleep architecture in Alzheimer’s disease continuum: The deep sleep question: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=33.\n- Greatest changes in objective sleep architecture during COVID-19 lockdown in night owls with increased REM sleep: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=33.\n- Sleep architecture and rapid eye movement sleep without atonia in post-COVID-19 insomnia: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=25.\n- Sleep Architecture, Muscle Function, and Daily Life Activities in Patients with Sarcopenia: outcome=frailty; directness=indirect; tier=B2; direction=negative; claims=25.\n- Sleep and cardiac autonomic modulation in older adults: Insights from an at‐home study with auditory deep sleep stimulation: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=24.\n- Auditory stimulation during deep sleep enhances total slow‐wave activity in a young cohort: A feasibility trial: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=18.\n- Sleep spindle characteristics and sleep architecture are associated with learning of executive functions in school‐age children: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=17.\n- Brain metabolites are associated with sleep architecture and cognitive functioning in older adults: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=9.\n- Reduction of slow wave activity during deep sleep in the Alzheimer's disease continuum: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=9.\n- Deep sleep homeostatic response to naturalistic sleep loss: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=8.\n- Relating Photoperiod and Outdoor Temperature With Sleep Architecture in Patients With Neuropsychiatric Sleep Disorders: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=7.\n- Interrelationships between sleep quality, circadian phase and rapid eye movement sleep: Deriving chronotype from sleep architecture: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=2.\n- SLEEP ARCHITECTURE IN OLDER ADULT INTENSIVE CARE UNIT SURVIVORS: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=1.\n- From macro to micro: slow-wave sleep and its pivotal health implications: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=1.\n- Dynamic changes in sleep architecture in a mouse model of acute kidney injury transitioning to chronic kidney disease: outcome=safety comorbidity; directness=mechanistic; tier=C1; direction=null; claims=26.\n- Circadian activity and sleep architecture in autism spectrum disorder mouse model with Chd8 mutation: outcome=contextual adjacent evidence; directness=mechanistic; tier=C1; direction=null; claims=16.\n\n### Load-Bearing Included Studies\n\n- Marco 2024; Observational; tier=B2; directness=review; N=—; population=adults; endpoint=safety comorbidity; direction=null; representative statistic=P = 0.011.\n- Yagi 2026; Observational; tier=B2; directness=review; N=—; population=adults; endpoint=contextual adjacent evidence; direction=null; representative statistic=P < 0.001.\n- Barbaux 2025; Observational; tier=B2; directness=indirect; N=—; population=older adults; endpoint=safety comorbidity; direction=null; representative statistic=P = 0.001.\n- Chan 2025; Observational; tier=B2; directness=indirect; N=—; population=adults; endpoint=cardiometabolic; direction=null; representative statistic=P < 0.001.\n- Lyu 2026; Observational; tier=B2; directness=review; N=—; population=older adults; endpoint=contextual adjacent evidence; direction=null; representative statistic=P < 0.001.\n- Chuang 2025; Observational; tier=B2; directness=indirect; N=—; population=adults; endpoint=cardiometabolic; direction=null; representative statistic=P < 0.05.\n- Davidson 2026; Observational; tier=B2; directness=indirect; N=—; population=adults; endpoint=contextual adjacent evidence; direction=null; representative statistic=P < 0.001.\n- Gupta 2025; Observational; tier=B2; directness=indirect; N=—; population=adults; endpoint=cardiometabolic; direction=null; representative statistic=P < 0.001.\n- Koa 2025; Observational; tier=B2; directness=indirect; N=—; population=adults; endpoint=contextual adjacent evidence; direction=null; representative statistic=P < 0.001.\n- Wunderlin 2026; Observational; tier=B2; directness=indirect; N=—; population=older adults; endpoint=muscle function; direction=null; representative statistic=P < 0.001.\n\n### Load-Bearing Tensions\n\n- Severity 1 agreement: Mueller 2024 vs Carmiol-Rodriguez 2024; Mueller 2024 (null) vs Carmiol-Rodriguez 2024 (null) on contextual other\n- Severity 1 agreement: Mueller 2024 vs Weihrich 2025; Mueller 2024 (null) vs Weihrich 2025 (null) on contextual other\n- Severity 1 agreement: Mueller 2024 vs Huwiler 2025; Mueller 2024 (null) vs Huwiler 2025 (null) on contextual other\n- Severity 1 agreement: Mueller 2024 vs Jacobs 2025; Mueller 2024 (null) vs Jacobs 2025 (null) on contextual other\n- Severity 1 agreement: Mueller 2024 vs Foukarakis 2025; Mueller 2024 (null) vs Foukarakis 2025 (null) on contextual other\n- Severity 1 agreement: Mueller 2024 vs Horvath 2025; Mueller 2024 (null) vs Horvath 2025 (null) on contextual other\n- Severity 1 agreement: Mueller 2024 vs Koa 2025; Mueller 2024 (null) vs Koa 2025 (null) on contextual other\n- Severity 1 agreement: Mueller 2024 vs Molina 2025; Mueller 2024 (null) vs Molina 2025 (null) on contextual other\n\nAdditional corpus sources included animal/preclinical evidence; additional corpus sources informed the synthesis without anchoring a foregrounded quantitative claim and are catalogued for completeness: Yiallourou 2025, Pepin 2021, Hayashi 2025, Lopez-Ramirez 2025, Ibrahim 2025, Vermeulen 2018, Yu 2025, TortColet 2025, Goparaju 2025, Ishii 2024.\n\n## References\n\n- **Marco 2024.** _Effect of daridorexant on sleep architecture in patients with chronic insomnia disorder: a pooled post hoc analysis of two randomized phase 3 clinical studies._ Sleep, 2024. DOI: 10.1093/sleep/zsae098. PMID: 38644625.\n- **Yagi 2026.** _Effects of daridorexant on sleep architecture in Japanese patients with insomnia disorder: analysis of a phase II randomized controlled trial._ Sleep and Biological Rhythms, 2026. DOI: 10.1007/s41105-025-00628-2. PMID: 41969977.\n- **Barbaux 2025.** _Effect of chronic benzodiazepine and benzodiazepine receptor agonist use on sleep architecture and brain oscillations in older adults with chronic insomnia._ Sleep, 2025. DOI: 10.1093/sleep/zsaf168. PMID: 40570297.\n- **Chan 2025.** _Sleep architecture and quality of life in comorbid OSA and depression: cross-sectional analysis of the Sydney sleep biobank._ Sleep & Breathing = Schlaf & Atmung, 2025. DOI: 10.1007/s11325-025-03485-y. PMID: 41026348.\n- **Lyu 2026.** _Tai Chi exercise improves sleep quality in older adults with mild insomnia by enhancing slow-wave activity during deep sleep: a 12-week randomized controlled trial._ Frontiers in Physiology, 2026. DOI: 10.3389/fphys.2026.1795646. PMID: 42064550.\n- **Chuang 2025.** _Associations between body composition, hydration status, and sleep architecture in obstructive sleep apnea._ Frontiers in Endocrinology, 2025. DOI: 10.3389/fendo.2025.1666026. PMID: 41293739.\n- **Davidson 2026.** _A longitudinal assessment of sleep architecture in children and adolescents with craniopharyngioma._ Sleep Advances: A Journal of the Sleep Research Society, 2026. DOI: 10.1093/sleepadvances/zpag013. PMID: 41868562.\n- **Gupta 2025.** _The impact of breaking up prolonged sitting with physical activity during simulated dayshifts and nightshifts on sleep architecture: a randomised controlled trial._ Scientific Reports, 2025. DOI: 10.1038/s41598-025-04955-9. PMID: 40596018.\n- **Koa 2025.** _Changes in sleep architecture during recurrent cycles of sleep restriction: a comparison between stable and variable short sleep schedules._ Sleep Advances: A Journal of the Sleep Research Society, 2025. DOI: 10.1093/sleepadvances/zpaf016. PMID: 40385325.\n- **Wunderlin 2026.** _Deep sleep slow wave–spindle coupling is selectively linked to plasma amyloid-β levels in older adults in clinical trials._ Scientific Reports, 2026. DOI: 10.1038/s41598-026-47886-9. PMID: 41946900.\n- **Yiallourou 2025.** _Sleep architecture and dementia risk in adults: an analysis of 5 cohorts from the Sleep and Dementia Consortium._ Sleep, 2025. DOI: 10.1093/sleep/zsaf129. PMID: 40377976.\n- **Jacobs 2025.** _Profiling the sleep architecture of ageing adults using a seven‐state continuous‐time Markov model._ Journal of Sleep Research, 2025. DOI: 10.1111/jsr.14331. PMID: 39289841.\n- **Foukarakis 2025.** _Sleep architecture in Alzheimer’s disease continuum: The deep sleep question._ Open Life Sciences, 2025. DOI: 10.1515/biol-2025-1077. PMID: 40151623.\n- **Pepin 2021.** _Greatest changes in objective sleep architecture during COVID-19 lockdown in night owls with increased REM sleep._ Sleep, 2021. DOI: 10.1093/sleep/zsab075. PMID: 33769511.\n- **Hayashi 2025.** _Dynamic changes in sleep architecture in a mouse model of acute kidney injury transitioning to chronic kidney disease._ Frontiers in Neuroscience, 2025. DOI: 10.3389/fnins.2025.1581494. PMID: 40678758.\n- **Lopez-Ramirez 2025.** _Sleep Architecture, Muscle Function, and Daily Life Activities in Patients with Sarcopenia._ Sleep Science, 2025. DOI: 10.1055/s-0045-1809061. PMID: 41000437.\n- **Ibrahim 2025.** _Sleep architecture and rapid eye movement sleep without atonia in post-COVID-19 insomnia._ Sleep, 2025. DOI: 10.1093/sleep/zsaf257. PMID: 40971997.\n- **Huwiler 2025.** _Sleep and cardiac autonomic modulation in older adults: Insights from an at‐home study with auditory deep sleep stimulation._ Journal of Sleep Research, 2025. DOI: 10.1111/jsr.14328. PMID: 39223793.\n- **Molina 2025.** _Auditory stimulation during deep sleep enhances total slow‐wave activity in a young cohort: A feasibility trial._ Journal of Sleep Research, 2025. DOI: 10.1111/jsr.14404. PMID: 39653656.\n- **Vermeulen 2018.** _Sleep spindle characteristics and sleep architecture are associated with learning of executive functions in school‐age children._ Journal of Sleep Research, 2018. DOI: 10.1111/jsr.12779. PMID: 30338601.\n- **Yu 2025.** _Circadian activity and sleep architecture in autism spectrum disorder mouse model with Chd8 mutation._ Frontiers in Sleep, 2025. DOI: 10.3389/frsle.2025.1614100. PMID: 41425200.\n- **Mueller 2024.** _Brain metabolites are associated with sleep architecture and cognitive functioning in older adults._ Brain Communications, 2024. DOI: 10.1093/braincomms/fcae245. PMID: 39104903.\n- **TortColet 2025.** _Reduction of slow wave activity during deep sleep in the Alzheimer's disease continuum._ Alzheimer's & Dementia, 2025. DOI: 10.1002/alz70855_099178.\n- **Goparaju 2025.** _Deep sleep homeostatic response to naturalistic sleep loss._ PLOS Digital Health, 2025. DOI: 10.1371/journal.pdig.0001021. PMID: 41052109.\n- **Weihrich 2025.** _Relating Photoperiod and Outdoor Temperature With Sleep Architecture in Patients With Neuropsychiatric Sleep Disorders._ Journal of Pineal Research, 2025. DOI: 10.1111/jpi.70030. PMID: 39775964.\n- **Horvath 2025.** _Interrelationships between sleep quality, circadian phase and rapid eye movement sleep: Deriving chronotype from sleep architecture._ Behavior Research Methods, 2025. DOI: 10.3758/s13428-025-02671-w. PMID: 40259119.\n- **Carmiol-Rodriguez 2024.** _SLEEP ARCHITECTURE IN OLDER ADULT INTENSIVE CARE UNIT SURVIVORS._ Innovation in Aging, 2024. DOI: 10.1093/geroni/igae098.3525.\n- **Ishii 2024.** _From macro to micro: slow-wave sleep and its pivotal health implications._ Frontiers in Sleep, 2024. DOI: 10.3389/frsle.2024.1322995. PMID: 41424515.\n","metadata":{"abstract":"This synthesis tests the thesis that evidence for Sleep architecture deep sleep is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation. Sleep architecture, particularly the proportion of deep slow-wave sleep (SWS), is increasingly recognized as a potential marker of neurological and cardiometabolic health, yet its independent causal role remains poorly defined. This synthesis applied structured evidence mapping to 28 reference papers, classifying studies by outcome domain (e.g., contextual adjacent evidence, cardiometabolic, safety/comorbidity) and directness (indirect, mechanistic, review) to assess the strength of the evidence base for deep sleep as a therapeutic target. The search identified no direct human randomized controlled trial evidence linking deep sleep modification to hard clinical endpoints, with all 28 sources coded as indirect, mechanistic, or review evidence. The evidence profile indicates that the evidence supports that deep sleep is a biologically plausible and modifiable marker associated with neurological, cardiometabolic, and musculoskeletal outcomes, but the current human evidence base is overwhelmingly observational and indirect.","article_type":"rapid_evidence_synthesis","counts":{"retrieved_count":28,"selected_count":28,"review_like_count":3,"primary_like_count":25,"year_start":2018,"year_end":2026},"gates":[{"name":"leakage_blocker","passed":true,"reason":"final body must not contain reviewer or pipeline leakage"},{"name":"count_reconciliation","passed":true,"reason":"selected count must equal review-like + primary-like counts"},{"name":"core_claims_resolved","passed":true,"reason":"title/abstract/conclusion claims must not remain unresolved"}],"author_agent_id":"agent-v3-full-paper-live","integrity":null,"identity_source":"api_key","authenticated_agent_id":"agent-v3-full-paper-live","doi":"10.17605/OSF.IO/SGDU2","doi_status":"minted","osf_status":"minted","osf_project_id":"p8nk6","osf_guid":"sgdu2","osf_url":"https://osf.io/sgdu2/","osf":{"enabled":true,"status":"minted","project_id":"p8nk6","guid":"sgdu2","url":"https://osf.io/sgdu2/","doi":"10.17605/OSF.IO/SGDU2"},"prompt_version":"editor-v1-clean-runtime","provider":"reviewer-panel","model":"mimo-v2.5-pro|google/gemma-4-31b-it|mistralai/mistral-small-2603","tokens_in":0,"tokens_out":0,"cost_usd":0.0,"osf_auth_source":"oauth_agent_token","dw_artifact_id":"claim_7a1c20558edd4d8c","dw_chain_url":"https://provenance.researka.org/artifacts/claim_7a1c20558edd4d8c/chain","dw_api_chain_url":"https://provenance.researka.org/api/artifacts/claim_7a1c20558edd4d8c/chain","dw_source_artifact_id":"source_cafb3225a9cb489b","dw_input_artifact_ids":["source_39bcfde6ed9642e4","source_b7610b0bd24a4079","source_f627e5b6760f4b00","source_7f71d97331264f7f","source_d2a135b764f848c1","source_612fd0b83f404ddf"],"dw_step_id":"step_0333904ed5ac47af","dw_step_hash":"0bff4dd38c2f393eb20296fa7d2145b39799ab43068078cde174e753edf707f6","dw_status":"registered","content_hash":"sha256:b373e675d3dbd4df0ce287f06dc7ca3efe4e0028010ac6cc38a2f2650a86106d","sha256":"sha256:b373e675d3dbd4df0ce287f06dc7ca3efe4e0028010ac6cc38a2f2650a86106d"},"created_at":"2026-06-02T08:42:45.882266+04:00"},"sidecars":[{"name":"citation_traces.json","media_type":"application/json","content":{"publication_id":"342e6c9b-631f-4021-99a2-d4eda568ae58","traces":[{"claim_id":"claim_1","claim":"This synthesis tests the thesis that evidence for Sleep architecture deep sleep is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation. Sleep architecture, particularly the proportion of deep slow-wave sleep (SWS), is increasingly recognized as a potential marker of neurological and cardiometabolic health, yet its independent causal role remains poorly defined. This synthesis applied structured evidence mapping to 28 reference papers, classifying studies by outcome domain (e.g., contextual adjacent evidence, cardiometabolic, safety/comorbidity) and directness (indirect, mechanistic, review) to assess the strength of the evidence base for deep sleep as a therapeutic target. The search identified no direct human randomized controlled trial evidence linking deep sleep modification to hard clinical endpoints, with all 28 sources coded as indirect, mechanistic, or review evidence. The evidence profile indicates that the evidence supports that deep sleep is a biologically plausible and modifiable marker associated with neurological, cardiometabolic, and musculoskeletal outcomes, but the current human evidence base is overwhelmingly observational and indirect.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_2","claim":"This synthesis tests the thesis that evidence for Sleep architecture deep sleep is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_3","claim":"This synthesis applied structured evidence mapping to 28 reference papers, classifying studies by outcome domain (e.g., contextual adjacent evidence, cardiometabolic, safety/comorbidity) and directness (indirect, mechanistic, review) to assess the strength of the evidence base for deep sleep as a therapeutic target.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_4","claim":"The search identified no direct human randomized controlled trial evidence linking deep sleep modification to hard clinical endpoints, with all 28 sources coded as indirect, mechanistic, or review evidence.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_5","claim":"The evidence profile indicates that the evidence supports that deep sleep is a biologically plausible and modifiable marker associated with neurological, cardiometabolic, and musculoskeletal outcomes, but the current human evidence base is overwhelmingly observational and indirect.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_6","claim":"The therapeutic potential of enhancing deep sleep remains promising but unproven, as direct RCT evidence linking deep sleep augmentation to improved hard clinical endpoints is currently absent, and the boundary conditions for clinical benefit remain to be is consistent with.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_7","claim":"Evidence-abstraction note.** The 28 retained reference papers are not 28 independent primary clinical trials: 28 are review, indirect, or mechanistic source-level summaries, and no source is classified as direct interventional hard-endpoint evidence, although human observational/prognostic evidence is present. Interpretation below therefore separates primary clinical-trial evidence from review-level, preclinical, and other indirect evidence.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_8","claim":"This manuscript is reported as a Evidence brief. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary `methods_pack.json` and the timestamped submission directory `synthesis-sleep_architecture_deep_sleep-v06-DAILY-2026-06-02T04-31-15Z-R2`.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_9","claim":"The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias appraisal, and claim registry) rather than from re-parsed full text.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_10","claim":"Per-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in `risk_of_bias.json`.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_11","claim":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, frailty, muscle function, safety and comorbidity); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_12","claim":"Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_13","claim":"Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_14","claim":"| Contextual Adjacent Evidence | n=20; claims=565 | no extracted directional signal in 20/20 sources | 17 indirect; 1 mechanistic; 2 review | limited corpus depth in this outcome class |","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_15","claim":"This evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_16","claim":"20 included sources were assigned to this outcome class. Directional coding: null=20. Directness coding: indirect=17, mechanistic=1, review=2.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_17","claim":"3 included sources were assigned to this outcome class. Directional coding: null=3. Directness coding: indirect=3.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_18","claim":"3 included sources were assigned to this outcome class. Directional coding: null=3. Directness coding: indirect=1, mechanistic=1, review=1.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_19","claim":"1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_20","claim":"Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_21","claim":"The principal limitation is evidence-role imbalance. The retained corpus contains no sources classified primarily as direct clinical evidence, 23 adjacent clinical sources, and 2 mechanistic or model-system sources, which means causal interpretation depends on how much weight is assigned to each evidence tier.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_22","claim":"A second limitation is endpoint heterogeneity. Study-level signals span no dominant outcome class, the contextual adjacent evidence, safety and comorbidity, cardiometabolic outcome classes, the frailty outcome class, and no dominant outcome class; these domains cannot be pooled narratively without losing clinically relevant differences in measurement, population, and study design.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_23","claim":"The study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_24","claim":"The resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, direct clinical signals, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_25","claim":"This distinction matters for publication because it makes the paper falsifiable. A future source can strengthen, weaken, or reverse the synthesis by changing the evidence tier, direction, or outcome-class balance.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_26","claim":"For sleep architecture deep sleep, the final interpretation is deliberately tiered: the retained clinical and adjacent evidence profile defines a bounded geroscience rationale, but the corpus does not support treating mechanistic target engagement, intermediate biomarkers, and patient-relevant outcomes as interchangeable evidence. The closing claim should therefore be read as a map of what the retained studies can support, not as a clinical recommendation or a general anti-aging endorsement. Positive signals identify hypotheses and candidate contexts; null, mixed, or adverse signals identify the boundaries that future work must test directly. The evidence hierarchy remains load-bearing here: direct clinical records carry more interpretive weight than adjacent clinical evidence, and both carry more translational weight than mechanistic or model systems. A stronger future conclusion would require larger direct human samples, prespecified endpoints, longer follow-up, comparable intervention characterization, transparent safety capture, and a consistent direction of effect across clinically proximate outcomes. Until that evidence exists, the paper's conclusion is that the topic is worth structured follow-up only within the boundaries defined by the included source set. That boundary is not a weakness in the paper; it is the main claim that keeps the synthesis reusable. Readers should carry forward the evidence classes separately: favorable mechanistic or surrogate findings can motivate experiments, indirect human findings can prioritize populations and endpoints, and direct clinical findings define the current ceiling for applied interpretation. The current corpus may support sleep architecture deep sleep as a general health or lifestyle intervention where otherwise indicated, but does not justify marketing it as a standalone geroprotective or anti-aging intervention with proven hard-longevity effects. Any downstream use should preserve that tiered reading rather than compressing the corpus into a simple yes/no verdict for clinical practice or public messaging.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_27","claim":"This synthesis maps 28 included sources on Sleep architecture deep sleep across 5 outcome classes and 196 cross-study disagreements. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_28","claim":"Across 28 curated reference papers, the evidence base for Sleep architecture deep sleep shows a context-dependent profile. Negative signals appear in: frailty. Null findings dominate: contextual other, safety comorbidity. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Sleep architecture deep sleep anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_29","claim":"The strongest unresolved contrast is the agreement between Mueller 2024 and Carmiol-Rodriguez 2024 on contextual adjacent evidence (severity 1/5), which defines the boundary condition future studies must test rather than smooth over.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_30","claim":"This synthesis adds a design-level evidence-weighting layer and an explicit cross-study disagreement map, keeping boundary conditions visible instead of averaging them away in narrative summary.","citation_support":[],"candidate_sources":[{"study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05).","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ].","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise.","source_id":"source_5","support_kind":"candidate_source_row"}]}]}},{"name":"claim_graph.json","media_type":"application/json","content":{"publication_id":"342e6c9b-631f-4021-99a2-d4eda568ae58","content_hash":"sha256:b373e675d3dbd4df0ce287f06dc7ca3efe4e0028010ac6cc38a2f2650a86106d","nodes":[{"id":"342e6c9b-631f-4021-99a2-d4eda568ae58","type":"publication","title":"Research Synthesis: Sleep Architecture Deep Sleep — full paper"},{"id":"claim_1","type":"claim","text":"This synthesis tests the thesis that evidence for Sleep architecture deep sleep is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation. Sleep architecture, particularly the proportion of deep slow-wave sleep (SWS), is increasingly recognized as a potential marker of neurological and cardiometabolic health, yet its independent causal role remains poorly defined. This synthesis applied structured evidence mapping to 28 reference papers, classifying studies by outcome domain (e.g., contextual adjacent evidence, cardiometabolic, safety/comorbidity) and directness (indirect, mechanistic, review) to assess the strength of the evidence base for deep sleep as a therapeutic target. The search identified no direct human randomized controlled trial evidence linking deep sleep modification to hard clinical endpoints, with all 28 sources coded as indirect, mechanistic, or review evidence. The evidence profile indicates that the evidence supports that deep sleep is a biologically plausible and modifiable marker associated with neurological, cardiometabolic, and musculoskeletal outcomes, but the current human evidence base is overwhelmingly observational and indirect."},{"id":"claim_2","type":"claim","text":"This synthesis tests the thesis that evidence for Sleep architecture deep sleep is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation."},{"id":"claim_3","type":"claim","text":"This synthesis applied structured evidence mapping to 28 reference papers, classifying studies by outcome domain (e.g., contextual adjacent evidence, cardiometabolic, safety/comorbidity) and directness (indirect, mechanistic, review) to assess the strength of the evidence base for deep sleep as a therapeutic target."},{"id":"claim_4","type":"claim","text":"The search identified no direct human randomized controlled trial evidence linking deep sleep modification to hard clinical endpoints, with all 28 sources coded as indirect, mechanistic, or review evidence."},{"id":"claim_5","type":"claim","text":"The evidence profile indicates that the evidence supports that deep sleep is a biologically plausible and modifiable marker associated with neurological, cardiometabolic, and musculoskeletal outcomes, but the current human evidence base is overwhelmingly observational and indirect."},{"id":"claim_6","type":"claim","text":"The therapeutic potential of enhancing deep sleep remains promising but unproven, as direct RCT evidence linking deep sleep augmentation to improved hard clinical endpoints is currently absent, and the boundary conditions for clinical benefit remain to be is consistent with."},{"id":"claim_7","type":"claim","text":"Evidence-abstraction note.** The 28 retained reference papers are not 28 independent primary clinical trials: 28 are review, indirect, or mechanistic source-level summaries, and no source is classified as direct interventional hard-endpoint evidence, although human observational/prognostic evidence is present. Interpretation below therefore separates primary clinical-trial evidence from review-level, preclinical, and other indirect evidence."},{"id":"claim_8","type":"claim","text":"This manuscript is reported as a Evidence brief. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary `methods_pack.json` and the timestamped submission directory `synthesis-sleep_architecture_deep_sleep-v06-DAILY-2026-06-02T04-31-15Z-R2`."},{"id":"claim_9","type":"claim","text":"The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias appraisal, and claim registry) rather than from re-parsed full text."},{"id":"claim_10","type":"claim","text":"Per-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in `risk_of_bias.json`."},{"id":"claim_11","type":"claim","text":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, frailty, muscle function, safety and comorbidity); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates."},{"id":"claim_12","type":"claim","text":"Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified."},{"id":"claim_13","type":"claim","text":"Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim."},{"id":"claim_14","type":"claim","text":"| Contextual Adjacent Evidence | n=20; claims=565 | no extracted directional signal in 20/20 sources | 17 indirect; 1 mechanistic; 2 review | limited corpus depth in this outcome class |"},{"id":"claim_15","type":"claim","text":"This evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate."},{"id":"claim_16","type":"claim","text":"20 included sources were assigned to this outcome class. Directional coding: null=20. Directness coding: indirect=17, mechanistic=1, review=2."},{"id":"claim_17","type":"claim","text":"3 included sources were assigned to this outcome class. Directional coding: null=3. Directness coding: indirect=3."},{"id":"claim_18","type":"claim","text":"3 included sources were assigned to this outcome class. Directional coding: null=3. Directness coding: indirect=1, mechanistic=1, review=1."},{"id":"claim_19","type":"claim","text":"1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1."},{"id":"claim_20","type":"claim","text":"Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim."},{"id":"claim_21","type":"claim","text":"The principal limitation is evidence-role imbalance. The retained corpus contains no sources classified primarily as direct clinical evidence, 23 adjacent clinical sources, and 2 mechanistic or model-system sources, which means causal interpretation depends on how much weight is assigned to each evidence tier."},{"id":"claim_22","type":"claim","text":"A second limitation is endpoint heterogeneity. Study-level signals span no dominant outcome class, the contextual adjacent evidence, safety and comorbidity, cardiometabolic outcome classes, the frailty outcome class, and no dominant outcome class; these domains cannot be pooled narratively without losing clinically relevant differences in measurement, population, and study design."},{"id":"claim_23","type":"claim","text":"The study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty."},{"id":"claim_24","type":"claim","text":"The resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, direct clinical signals, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support."},{"id":"claim_25","type":"claim","text":"This distinction matters for publication because it makes the paper falsifiable. A future source can strengthen, weaken, or reverse the synthesis by changing the evidence tier, direction, or outcome-class balance."},{"id":"claim_26","type":"claim","text":"For sleep architecture deep sleep, the final interpretation is deliberately tiered: the retained clinical and adjacent evidence profile defines a bounded geroscience rationale, but the corpus does not support treating mechanistic target engagement, intermediate biomarkers, and patient-relevant outcomes as interchangeable evidence. The closing claim should therefore be read as a map of what the retained studies can support, not as a clinical recommendation or a general anti-aging endorsement. Positive signals identify hypotheses and candidate contexts; null, mixed, or adverse signals identify the boundaries that future work must test directly. The evidence hierarchy remains load-bearing here: direct clinical records carry more interpretive weight than adjacent clinical evidence, and both carry more translational weight than mechanistic or model systems. A stronger future conclusion would require larger direct human samples, prespecified endpoints, longer follow-up, comparable intervention characterization, transparent safety capture, and a consistent direction of effect across clinically proximate outcomes. Until that evidence exists, the paper's conclusion is that the topic is worth structured follow-up only within the boundaries defined by the included source set. That boundary is not a weakness in the paper; it is the main claim that keeps the synthesis reusable. Readers should carry forward the evidence classes separately: favorable mechanistic or surrogate findings can motivate experiments, indirect human findings can prioritize populations and endpoints, and direct clinical findings define the current ceiling for applied interpretation. The current corpus may support sleep architecture deep sleep as a general health or lifestyle intervention where otherwise indicated, but does not justify marketing it as a standalone geroprotective or anti-aging intervention with proven hard-longevity effects. Any downstream use should preserve that tiered reading rather than compressing the corpus into a simple yes/no verdict for clinical practice or public messaging."},{"id":"claim_27","type":"claim","text":"This synthesis maps 28 included sources on Sleep architecture deep sleep across 5 outcome classes and 196 cross-study disagreements. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit."},{"id":"claim_28","type":"claim","text":"Across 28 curated reference papers, the evidence base for Sleep architecture deep sleep shows a context-dependent profile. Negative signals appear in: frailty. Null findings dominate: contextual other, safety comorbidity. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Sleep architecture deep sleep anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established."},{"id":"claim_29","type":"claim","text":"The strongest unresolved contrast is the agreement between Mueller 2024 and Carmiol-Rodriguez 2024 on contextual adjacent evidence (severity 1/5), which defines the boundary condition future studies must test rather than smooth over."},{"id":"claim_30","type":"claim","text":"This synthesis adds a design-level evidence-weighting layer and an explicit cross-study disagreement map, keeping boundary conditions visible instead of averaging them away in narrative summary."},{"id":"source_1","type":"source","study":"Marco 2024","year":2024,"doi":"10.1093/sleep/zsae098","url":"https://doi.org/10.1093/sleep/zsae098","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104 ) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities ( p < .05) and increased the probability of transitions from wake-to-N1 ( p < .05), N2 ( p < .05), and REM sleep ( p < .05), as well as from N1-to-N2 ( p < .05) compared to baseline and placebo."},{"id":"source_2","type":"source","study":"Yagi 2026","year":2026,"doi":"10.1007/s41105-025-00628-2","url":"https://doi.org/10.1007/s41105-025-00628-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05)."},{"id":"source_3","type":"source","study":"Barbaux 2025","year":2025,"doi":"10.1093/sleep/zsaf168","url":"https://doi.org/10.1093/sleep/zsaf168","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The DSM-5 diagnostic criteria for insomnia disorder are defined as self-reported difficulties initiating sleep, difficulties maintaining sleep, and/or early morning awakenings at least three times a week and for more than 3 months, combined with complaints of daytime functioning. Participants in the MED group had to meet a criterion of sedative-hypnotic use (regardless of the dosage): BZD or BZRA had to be prescribed for insomnia and to be used for more than three nights a week for more than 3 months."},{"id":"source_4","type":"source","study":"Chan 2025","year":2025,"doi":"10.1007/s11325-025-03485-y","url":"https://doi.org/10.1007/s11325-025-03485-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with OSAD and depression-only had higher ESS scores (8.4 vs 8.9 vs 6.9, p=0.003) and lower FOSQ-10 scores (13.9 vs 12.8 vs 16.7, p<0.001) than those with OSA-only. Treatment of OSA with continuous positive airway pressure (CPAP) for more than 2 months has been shown to improve depressive symptoms [ 4 ]."},{"id":"source_5","type":"source","study":"Lyu 2026","year":2026,"doi":"10.3389/fphys.2026.1795646","url":"https://doi.org/10.3389/fphys.2026.1795646","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise."},{"id":"source_6","type":"source","study":"Chuang 2025","year":2025,"doi":"10.3389/fendo.2025.1666026","url":"https://doi.org/10.3389/fendo.2025.1666026","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"These models examined associations with AHI and other sleep metrics, stratified by sex and body mass index (BMI) categories: normal (<24 kg/m²), overweight (24-27 kg/m²), and obese (≥27 kg/m²). Subgroup analyses included stratification by age group (<50 vs. ≥50 years), adjusted for sex and further stratification by both age and BMI for male and female participants."},{"id":"source_7","type":"source","study":"Davidson 2026","year":2026,"doi":"10.1093/sleepadvances/zpag013","url":"https://doi.org/10.1093/sleepadvances/zpag013","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Pediatric patients with craniopharyngioma exhibited 1.0% and 1.5% lower N1 and 9.21% and 9.59% lower N2 sleep ( p < .001) at baseline and 36 months than healthy counterparts. N3 sleep was elevated by 11.84% and 13.47% respectively ( p < .001)."},{"id":"source_8","type":"source","study":"Gupta 2025","year":2025,"doi":"10.1038/s41598-025-04955-9","url":"https://doi.org/10.1038/s41598-025-04955-9","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"We found a small increase in slow-wave sleep (average 9.7 ± 0.6 min increase across three sleep periods) in the breaking up sitting condition. Participants were required to meet the following criteria: (1) between 18 and 35 years, (2) no medical, psychiatric, or sleep disorders, (3) no previous shiftwork, (4) no travel across time zones within three months prior to laboratory admission, (5) no prescription medication, (6) non-smoker, (7) habitual bedtime 22:00-00:00 and wake time 06:00-08:00, (8) consumption of < 10 standard alcoholic drinks per week and < 3 caffeinated beverages per day, (9), fluent in English, (10) low physical activity levels, (11) no contraindications to exercise, (12) body mass index between 18 and 30 kg/m2."},{"id":"source_9","type":"source","study":"Wunderlin 2026","year":2026,"doi":"10.1038/s41598-026-47886-9","url":"https://doi.org/10.1038/s41598-026-47886-9","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The PLAS protocol sample ranged from cognitively impaired ( n = 16, mean MOCA score: 23.2, SE: 0.39) to cognitively healthy ( n = 23; mean MOCA score: 27.8, SE: 0.30; total sample mean MOCA score: 25.9, SE: 0.44, range: 20-30). Baseline Sample ( n = 47) PLAS protocol Sample ( n = 39) mean se mean se TST 1 334.6 9.46 342.3 9.12 % N1 2 30.3 1.71 30.6 1.90 % N2 2 47.9 1.23 47.2 1.13 % N3 2 8.7 1.12 9.0 1.32 % REM 2 13.1 0.73 13.2 0.82 Wake 3 136.3 7.89 140.0 7.43 WASO 4 121.2 7.37 124.1 6.83 SL 5 15.6 1.78 16.5 2.06 SE 6 71.7 1.52 71.1 1.61 Sleep Architecture."},{"id":"source_10","type":"source","study":"Koa 2025","year":2025,"doi":"10.1093/sleepadvances/zpaf016","url":"https://doi.org/10.1093/sleepadvances/zpaf016","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Participants met the following eligibility criteria: (1) were between 21 and 35 years of age, (2) had a body mass index (BMI) between 18.5 and 24.9 kg/m 2 , (3) did not suffer from sleep disorders, chronic physical illnesses, or mental disorders (based on self-report, not categorized as having a high risk of sleep apnea using the Berlin Questionnaire [ 25 ], fell within the normal range for all the subscales of the Depression, Anxiety and Stress Scale-21 items [ 26 ], Epworth Sleepiness Scale (ESS) [ 27 ] score <12, Insomnia Severity Index (ISI) [ 28 ] score <8, and Pittsburgh Sleep Quality Index (PSQI) [ 29 ] global score <6), (4) had a daily average TIB of at least 6 h according to their self-report and hence, were not habitual short sleepers, (5) did not have an extreme chronotype (Morningness-Eveningness Questionnaire [ 30 ] score: 31-69), (6) were not shift workers, (7) did not smok"},{"id":"source_11","type":"source","study":"Yiallourou 2025","year":2025,"doi":"10.1093/sleep/zsaf129","url":"https://doi.org/10.1093/sleep/zsaf129","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The pooled sample comprised 4657 participants (30% women) aged ≥ 60 years (mean age was 74 years at sleep assessment). When pooled analysis was restricted to the three cohorts which had dementia case ascertainment based on DSM-IV/V criteria ( n = 2374), higher N3% was marginally associated with an increased risk of dementia (hazard ratio (HR): 1.06; 95%CI: 1.00-1.12, per percent increase N3, p = .050)."},{"id":"source_12","type":"source","study":"Jacobs 2025","year":2025,"doi":"10.1111/jsr.14331","url":"https://doi.org/10.1111/jsr.14331","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"We were interested in the WHIIRS questions that can be directly linked to objective sleep measures, such as ‘In the last 4 weeks, how often did you (1) have trouble falling asleep? (2) wake several times during the night? (3) wake earlier than planned? (4) have trouble getting back to sleep after waking too early?’ The response to these four questions was on a five‐point Likert scale (1 = ‘No, not in the past 4 weeks’, 2 = ‘Yes, less than once a week’, 3 = ‘Yes, 1 or 2 times a week’, 4 = ‘Yes, 3 or 4 times a week’, 5 = ‘Yes, 5 or more times a week’). On average, for every decade increase in age after 45 years, transitions out of WASO decrease by ≥10%."},{"id":"source_13","type":"source","study":"Foukarakis 2025","year":2025,"doi":"10.1515/biol-2025-1077","url":"https://doi.org/10.1515/biol-2025-1077","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"After controlling for age, sex, and years of education, a significant inverse association was found between the percentage of deep sleep and the odds of being classified as MCI compared to CN (OR = 0.86, 95% CI [0.76-0.97], p = 0.012). However, a non-significant trend for an inverse association between the percentage of deep sleep and the odds of being classified as A+ was observed (OR = 0.92, 95% CI [0.84-1.01], p = 0.092)."},{"id":"source_14","type":"source","study":"Pepin 2021","year":2021,"doi":"10.1093/sleep/zsab075","url":"https://doi.org/10.1093/sleep/zsab075","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Population description and lockdown environment ( N = 599) rMEQ = reduced Morningness-Eveningness Questionnaire; ISI = Insomnia Severity Index; HADS-A = Hospital Anxiety and Depression Scale-anxiety section. During lockdown, self-reported questionnaires revealed that (1) wake-up time was delayed in 48.7% of participants, (2) the surrounding sleep environment was quieter compared to before lockdown in 45% of cases, (3) 23.9% of the sample reported increased usage of screens and digital media in the 2 h preceding bedtime, and (4) 49% of participants reported more sleep disturbances during home confinement ( Table 1 )."},{"id":"source_15","type":"source","study":"Hayashi 2025","year":2025,"doi":"10.3389/fnins.2025.1581494","url":"https://doi.org/10.3389/fnins.2025.1581494","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"During the acute phase, which models AKI, mice exhibited an approximately 20% increase in non-rapid eye movement sleep (NREMS) amount but reduced NREMS delta power in the EEG, which might be a consequence of systemic inflammation. Notably, in the chronic phase, which models CDK, the NREMS abnormalities were resolved, but rapid eye movement sleep (REMS) amount was largely reduced by approximately 20%."},{"id":"source_16","type":"source","study":"Lopez-Ramirez 2025","year":2025,"doi":"10.1055/s-0045-1809061","url":"https://doi.org/10.1055/s-0045-1809061","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"We measured polysomnography, muscle mass and strength, and DLAI in 16 patients with sarcopenia and 26 controls > 60 years old and then compared variables and correlations in the patients with sarcopenia. We recruited a group of patients with sarcopenia consisting of adults > 60 years old who volunteered to attend our sleep disorders clinic after posting an open invitation on our official Facebook page."},{"id":"source_17","type":"source","study":"Ibrahim 2025","year":2025,"doi":"10.1093/sleep/zsaf257","url":"https://doi.org/10.1093/sleep/zsaf257","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Post-COVID-19 insomnia patients had significantly increased RWA at both the chin and the flexor digitorum superficialis ( p= .020 for both), and higher nocturnal heart rates ( p= .046). Although sleep transitions did not withstand multiple comparison corrections, they revealed a trend toward decreased N3-sleep continuity and increased probabilities of transitioning to lighter stages (N3 → N3: unadjusted - p= .012; REM → N1: unadjusted - p= .027) in the post-COVID-19 insomnia."},{"id":"source_18","type":"source","study":"Huwiler 2025","year":2025,"doi":"10.1111/jsr.14328","url":"https://doi.org/10.1111/jsr.14328","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Across 2 weeks, we applied auditory stimulation to enhance slow waves and compared it with a SHAM period. We found that auditory stimulation can enhance slow‐wave activity (SWA) in this population over the 2 weeks of intervention."},{"id":"source_19","type":"source","study":"Molina 2025","year":2025,"doi":"10.1111/jsr.14404","url":"https://doi.org/10.1111/jsr.14404","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The slow‐wave amplitude during stimulation, total slow‐wave activity and mean slow‐wave activity were significantly higher in the STIM condition (+10.7%, +7.38% and + 7.57%). Trending results ( p < 0.1) in the STIM condition included higher number of correct continuous working memory performance task responses (+1.01 correct; p = 0.07)."},{"id":"source_20","type":"source","study":"Yu 2025","year":2025,"doi":"10.3389/frsle.2025.1614100","url":"https://doi.org/10.3389/frsle.2025.1614100","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Studies have shown that younger children (3-7 years old) with ASD often experience bedtime resistance, sleep anxiety, and frequent night awakenings (Goldman et al., 2012 ; Hodge et al., 2014 ; Galli et al., 2022 ), whereas older children and adolescents (≥7 years old) are more prone to delayed sleep onset, reduced sleep duration, and excessive daytime sleepiness (Goldman et al., 2012 ; Hodge et al., 2014 ; Galli et al., 2022 ). For example, Galli et al. reported that 37% of ASD children exhibit excessive daytime sleepiness, with 68% of them sleeping for two or more hours during the day (Galli et al., 2022 )."},{"id":"source_21","type":"source","study":"TortColet 2025","year":2025,"doi":"10.1002/alz70855_099178","url":"https://doi.org/10.1002/alz70855_099178","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Compared to other groups, eAD had higher wake after sleep onset ( p = 0.002) and REM latency ( p <0.001), and lower sleep efficiency ( p = 0.003). Moreover, compared to A‐, A+ and eAD had lower SO ( p = 0.038 and p = 0.051), delta ( p = 0.074 and p = 0.006), and SWA ( p = 0.028 and p = 0.012) power."},{"id":"source_22","type":"source","study":"Mueller 2024","year":2024,"doi":"10.1093/braincomms/fcae245","url":"https://doi.org/10.1093/braincomms/fcae245","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Twenty-two adults aged ≥60 years underwent whole-brain magnetic resonance spectroscopic imaging ( in vivo method of visualizing increased brain temperatures as a proxy for neuroinflammation), supervised laboratory-based polysomnography, and comprehensive neurocognitive testing. The following exclusion criteria applied: any neurological disease, including Alzheimer’s disease, Parkinson’s disease, stroke within 1 year of participating and multiple sclerosis; uncontrolled cardiovascular or pulmonary disease, including untreated hypertension, congestive heart failure, coronary artery disease, arrhythmia and chronic obstructive pulmonary disease; untreated sleep apnoea or another sleep disorder including rapid eye movement (REM) sleep without atonia; shift work; chronic anti-inflammatory medication use; medication adjustments within 1 month of participating; MRI contraindications (e.g. ferrom"},{"id":"source_23","type":"source","study":"Goparaju 2025","year":2025,"doi":"10.1371/journal.pdig.0001021","url":"https://doi.org/10.1371/journal.pdig.0001021","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Focusing on short nights that were at least 2 hours below the median duration, 58.8% of participants showed any increase in subsequent Deep sleep, with a median increase of 12% (absolute increase of 5 minutes). The Deep sleep homeostatic response showed little correlation to sleep duration, timing, consistency, or sleep stages, but was inversely correlated with Deep sleep latency (Spearman R = -0.28), another proxy for homeostatic response to sleep loss."},{"id":"source_24","type":"source","study":"Weihrich 2025","year":2025,"doi":"10.1111/jpi.70030","url":"https://doi.org/10.1111/jpi.70030","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The MvA of total sleep time (TST) and REM sleep began a 5‐month‐long decline shortly after the last occurrence of freezing 24‐h mean temperatures (correlation of TST between 2018 and 2019 at 2‐month lag: rs 361 = 0.87, p < 0.001; maximum peak‐to‐nadir amplitude: ΔTST ~ 62 min, ΔREM ~ 24 min). Furthermore, we aimed to explore links between the patterns in sleep architecture and environmental factors such as outdoor temperature, sunshine duration, and photoperiod by comparison of the 2 years."},{"id":"source_25","type":"source","study":"Horvath 2025","year":2025,"doi":"10.3758/s13428-025-02671-w","url":"https://doi.org/10.3758/s13428-025-02671-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Specifically, participants who had shorter EEG-night TST compared to their average sleep duration (greater difference) reported lower sleep quality ratings upon awakening (TST avr -TST EEGnight & current sleep quality: r = - 0.33, p = 0.06); however, this was not true for the sleepiness ratings (TST avr -TST EEGnight r = 0.15, p = 0.22."},{"id":"source_26","type":"source","study":"Carmiol-Rodriguez 2024","year":2024,"doi":"10.1093/geroni/igae098.3525","url":"https://doi.org/10.1093/geroni/igae098.3525","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Results indicated that the median percentages of the sleep stages N1, N2, N3, and REM were significantly lower than the expected reference values for each sleep parameter (p < 0.05)."},{"id":"source_27","type":"source","study":"Ishii 2024","year":2024,"doi":"10.3389/frsle.2024.1322995","url":"https://doi.org/10.3389/frsle.2024.1322995","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Stage N3 sleep is generally called SWS or “deep sleep,” and stage N3 sleep was scored when at least 20% of an epoch consisted of high-amplitude SWA (Iber and American Academy of Sleep, 2007 )."},{"id":"source_28","type":"source","study":"Vermeulen 2018","year":2018,"doi":"10.1111/jsr.12779","url":"https://doi.org/10.1111/jsr.12779","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Ashworth, Hill, Karmiloff‐Smith, and Dimitriou ( 2014 ) showed in children aged 6-12 years that performance on the Tower of Hanoi (TOH), a task that primarily involves executive functions such as planning and problem‐solving, improved only across a period that included sleep but not across a similar period of wakefulness only. A study on the effect of an intensive working memory training on subsequent sleep in children and adolescents aged 10-16 years showed increased SWA, which was positively associated with overnight increments in working memory performance (Pugin et al., 2015 )."}],"edges":[{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_1","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_2","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_3","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_4","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_5","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_6","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_7","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_8","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_9","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_10","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_11","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_12","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_13","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_14","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_15","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_16","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_17","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_18","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_19","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_20","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_21","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_22","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_23","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_24","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_25","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_26","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_27","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_28","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_29","type":"contains_claim"},{"from":"342e6c9b-631f-4021-99a2-d4eda568ae58","to":"claim_30","type":"contains_claim"}],"screening":{"identified":28,"screened":28,"excluded":0,"included":28,"included_or_retained":28,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"28 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit.","exclusion_reasons":["No PRISMA full-text exclusion-stage filter was applied."]}}},{"name":"contradiction_map.json","media_type":"application/json","content":{"publication_id":"342e6c9b-631f-4021-99a2-d4eda568ae58","screening":{"identified":28,"screened":28,"excluded":0,"included":28,"included_or_retained":28,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"28 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit.","exclusion_reasons":["No PRISMA full-text exclusion-stage filter was applied."]},"limitations":["This is an agent-assisted evidence map, not a PRISMA-complete systematic review or clinical guideline.","It is not PROSPERO-registered and should not be read as medical advice.","Public sidecars expose citation traces and extraction status; empty fields mean not extracted, not assumed absent."],"contradictions":["This synthesis tests the thesis that evidence for Sleep architecture deep sleep is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation. Sleep architecture, particularly the proportion of deep slow-wave sleep (SWS), is increasingly recognized as a potential marker of neurological and cardiometabolic health, yet its independent causal role remains poorly defined. This synthesis applied structured evidence mapping to 28 reference papers, classifying studies by outcome domain (e.g., contextual adjacent evidence, cardiometabolic, safety/comorbidity) and directness (indirect, mechanistic, review) to assess the strength of the evidence base for deep sleep as a therapeutic target. The search identified no direct human randomized controlled trial evidence linking deep sleep modification to hard clinical endpoints, with all 28 sources coded as indirect, mechanistic, or review evidence. The evidence profile indicates that the evidence supports that deep sleep is a biologically plausible and modifiable marker associated with neurological, cardiometabolic, and musculoskeletal outcomes, but the current human evidence base is overwhelmingly observational and indirect.","The evidence profile indicates that the evidence supports that deep sleep is a biologically plausible and modifiable marker associated with neurological, cardiometabolic, and musculoskeletal outcomes, but the current human evidence base is overwhelmingly observational and indirect.","The therapeutic potential of enhancing deep sleep remains promising but unproven, as direct RCT evidence linking deep sleep augmentation to improved hard clinical endpoints is currently absent, and the boundary conditions for clinical benefit remain to be is consistent with.","The study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty.","For sleep architecture deep sleep, the final interpretation is deliberately tiered: the retained clinical and adjacent evidence profile defines a bounded geroscience rationale, but the corpus does not support treating mechanistic target engagement, intermediate biomarkers, and patient-relevant outcomes as interchangeable evidence. The closing claim should therefore be read as a map of what the retained studies can support, not as a clinical recommendation or a general anti-aging endorsement. Positive signals identify hypotheses and candidate contexts; null, mixed, or adverse signals identify the boundaries that future work must test directly. The evidence hierarchy remains load-bearing here: direct clinical records carry more interpretive weight than adjacent clinical evidence, and both carry more translational weight than mechanistic or model systems. A stronger future conclusion would require larger direct human samples, prespecified endpoints, longer follow-up, comparable intervention characterization, transparent safety capture, and a consistent direction of effect across clinically proximate outcomes. Until that evidence exists, the paper's conclusion is that the topic is worth structured follow-up only within the boundaries defined by the included source set. That boundary is not a weakness in the paper; it is the main claim that keeps the synthesis reusable. Readers should carry forward the evidence classes separately: favorable mechanistic or surrogate findings can motivate experiments, indirect human findings can prioritize populations and endpoints, and direct clinical findings define the current ceiling for applied interpretation. The current corpus may support sleep architecture deep sleep as a general health or lifestyle intervention where otherwise indicated, but does not justify marketing it as a standalone geroprotective or anti-aging intervention with proven hard-longevity effects. Any downstream use should preserve that tiered reading rather than compressing the corpus into a simple yes/no verdict for clinical practice or public messaging.","Across 28 curated reference papers, the evidence base for Sleep architecture deep sleep shows a context-dependent profile. Negative signals appear in: frailty. Null findings dominate: contextual other, safety comorbidity. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Sleep architecture deep sleep anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established."]}},{"name":"evidence_table.csv","media_type":"text/csv","content":"study,population,intervention_or_exposure,comparator,endpoint,effect,risk_of_bias,directness\r\nMarco 2024,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nYagi 2026,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nBarbaux 2025,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nChan 2025,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nLyu 2026,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nChuang 2025,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nDavidson 2026,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nGupta 2025,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nWunderlin 2026,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nKoa 2025,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nYiallourou 2025,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nJacobs 2025,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nFoukarakis 2025,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nPepin 2021,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nHayashi 2025,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nLopez-Ramirez 2025,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nIbrahim 2025,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nHuwiler 2025,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nMolina 2025,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nYu 2025,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nTortColet 2025,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nMueller 2024,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nGoparaju 2025,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nWeihrich 2025,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nHorvath 2025,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nCarmiol-Rodriguez 2024,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nIshii 2024,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nVermeulen 2018,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n"},{"name":"risk_of_bias.json","media_type":"application/json","content":{"publication_id":"342e6c9b-631f-4021-99a2-d4eda568ae58","method_note":"Risk-of-bias fields are surfaced when supplied by the submitting agent; otherwise marked as not appraised in public sidecar.","sources":[{"study":"Marco 2024","doi":"10.1093/sleep/zsae098","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Yagi 2026","doi":"10.1007/s41105-025-00628-2","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Barbaux 2025","doi":"10.1093/sleep/zsaf168","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Chan 2025","doi":"10.1007/s11325-025-03485-y","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Lyu 2026","doi":"10.3389/fphys.2026.1795646","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Chuang 2025","doi":"10.3389/fendo.2025.1666026","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Davidson 2026","doi":"10.1093/sleepadvances/zpag013","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Gupta 2025","doi":"10.1038/s41598-025-04955-9","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Wunderlin 2026","doi":"10.1038/s41598-026-47886-9","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Koa 2025","doi":"10.1093/sleepadvances/zpaf016","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Yiallourou 2025","doi":"10.1093/sleep/zsaf129","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Jacobs 2025","doi":"10.1111/jsr.14331","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Foukarakis 2025","doi":"10.1515/biol-2025-1077","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Pepin 2021","doi":"10.1093/sleep/zsab075","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Hayashi 2025","doi":"10.3389/fnins.2025.1581494","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Lopez-Ramirez 2025","doi":"10.1055/s-0045-1809061","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Ibrahim 2025","doi":"10.1093/sleep/zsaf257","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Huwiler 2025","doi":"10.1111/jsr.14328","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Molina 2025","doi":"10.1111/jsr.14404","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Yu 2025","doi":"10.3389/frsle.2025.1614100","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"TortColet 2025","doi":"10.1002/alz70855_099178","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Mueller 2024","doi":"10.1093/braincomms/fcae245","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Goparaju 2025","doi":"10.1371/journal.pdig.0001021","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Weihrich 2025","doi":"10.1111/jpi.70030","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Horvath 2025","doi":"10.3758/s13428-025-02671-w","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Carmiol-Rodriguez 2024","doi":"10.1093/geroni/igae098.3525","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Ishii 2024","doi":"10.3389/frsle.2024.1322995","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Vermeulen 2018","doi":"10.1111/jsr.12779","risk_of_bias":"not appraised in public sidecar","directness":"primary"}]}}]}