Derivation Web

source_ffc81bd38ad14f89

by researka:v2 · 2026-06-21 18:18:22.382788+04:00

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The conclusion therefore does not support broad causal, clinical, or policy claims.", "type": "claim"}, {"id": "claim_2", "text": "We conducted an AI-assisted structured evidence synthesis across 14 curated human-aging studies, with every included citation tied to an auditable source describing design, outcome class, directness tier, and effect direction; cross-domain tensions between mechanistic and clinical evidence, and between direct and indirect anchors, were preserved rather than collapsed.", "type": "claim"}, {"id": "claim_3", "text": "Methodologically, Schrenk 2023 is a registered online-exercise RCT protocol without reported empirical findings and therefore cannot serve as a direct mechanistic/biomarker human-evidence anchor; we treat it as a planned study whose eventual results would address the mechanism-to-clinic gap rather than as evidence itself.", "type": "claim"}, {"id": "claim_4", "text": "Interpretation below therefore separates primary clinical-trial evidence from review-level, preclinical, and other indirect evidence.", "type": "claim"}, {"id": "claim_5", "text": "This synthesis evaluates evidence on cognition durations across 14 included source papers and 341 high-confidence extracted claims. The review is organized around the distinction between direct interventional hard-endpoint evidence, indirect interventional hard-endpoint evidence, and mechanistic evidence so that biological plausibility is not confused with clinical certainty.", "type": "claim"}, {"id": "claim_6", "text": "The corpus contains 2 direct clinical sources, 12 adjacent clinical sources, and no sources classified primarily as mechanistic or model-system evidence. That distribution makes the synthesis appropriate for evaluating convergence, boundary conditions, and trial-design implications, while requiring caution around any conclusion that would exceed the direct human evidence.", "type": "claim"}, {"id": "claim_7", "text": "The thesis is: Across 14 curated reference papers, the evidence base for Cognition shows a context-dependent profile. Positive signals appear in: dosing pharmacokinetics, cognitive. Negative signals appear in: dosing pharmacokinetics. Null findings dominate: contextual other. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Cognition 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. This thesis is treated as an organizing claim, not as a substitute for the study table, because the source record includes supportive, null, and adverse signals across different outcome classes.", "type": "claim"}, {"id": "claim_8", "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.", "type": "claim"}, {"id": "claim_9", "text": "The mechanistic layer is most useful when it explains why a trial signal might appear or fail to appear. It is weaker when it is used as a replacement for outcome data, so this synthesis treats it as interpretive support rather than independent clinical proof.", "type": "claim"}, {"id": "claim_10", "text": "Null findings have a specific role in this evidence model. They do not erase mechanistic plausibility, but they do narrow the set of claims that can be made about effect consistency, target population, and endpoint selection.", "type": "claim"}, {"id": "claim_11", "text": "Adverse or negative signals are likewise retained in the main interpretation. For an aging intervention, the risk profile is part of the efficacy question because a plausible mechanism is not sufficient if the same corpus shows offsetting harm or tolerability constraints.", "type": "claim"}, {"id": "claim_12", "text": "The evidence base also distinguishes breadth from certainty. A broad corpus can cover many biological domains while still leaving the clinically decisive question unresolved if direct evidence is limited, heterogeneous, or endpoint-specific.", "type": "claim"}, {"id": "claim_13", "text": "The background evidence for cognition durations is heterogeneous rather than uniformly confirmatory. Direct clinical sources such as Asteasu 2024, Schrenk 2023 are interpreted separately from mechanistic studies such as the retained evidence base, because these evidence roles answer different questions about aging biology and clinical translation.", "type": "claim"}, {"id": "claim_14", "text": "The direct evidence establishes what has been observed in human or adjacent clinical settings. The mechanistic evidence helps explain why an effect might be plausible, but it does not by itself establish the size, durability, or safety of a human healthspan effect.", "type": "claim"}, {"id": "claim_15", "text": "Across the retained sources, positive signals cluster around the dosing and pharmacokinetics, cognitive outcome classes; null signals around the contextual adjacent evidence outcome class; and negative or adverse signals around the dosing and pharmacokinetics outcome class. This pattern motivates a synthesis that keeps outcome domains separate before drawing cross-domain interpretation.", "type": "claim"}, {"id": "claim_16", "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.", "type": "claim"}, {"id": "claim_17", "text": "The resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, observed direct signals when present, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support.", "type": "claim"}, {"id": "claim_18", "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 sidecar when populated, and claim registry) rather than from re-parsed full text.", "type": "claim"}, {"id": "claim_19", "text": "Risk-of-bias framework assignment follows study design (RoB-2 for RCTs, ROBINS-I for non-randomised studies, AMSTAR-2 for systematic reviews / meta-analyses). Public appraisal claims are limited to populated `risk_of_bias.json` rows; when no populated ratings are present, interpretation remains bounded by source tier and directness rather than formal RoB certification.", "type": "claim"}, {"id": "claim_20", "text": "Evidence-tension synthesis: claims grouped by outcome class (cognitive, contextual adjacent evidence, dosing and pharmacokinetics, muscle function); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.", "type": "claim"}, {"id": "claim_21", "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.", "type": "claim"}, {"id": "claim_22", "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.", "type": "claim"}, {"id": "claim_23", "text": "| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |", "type": "claim"}, {"id": "claim_24", "text": "| Contextual Adjacent Evidence | n=8; claims=139 | no extracted directional signal in 6/8 sources | 1 direct; 5 indirect; 2 review | limited corpus depth in this outcome class |", "type": "claim"}, {"id": "claim_25", "text": "Contextual Adjacent Evidence: n=8; claims=139; no extracted directional signal in 6/8 sources | directness: 1 direct; 5 indirect; 2 review; main limitation: directionally heterogeneous.", "type": "claim"}, {"id": "claim_26", "text": "Summary of the curated cognitive corpus. The cognitive outcome class is supported by three curated sources spanning three distinct designs. Siette 2025 is a systematic review on behavioural sleep programs. Association of Objective Sleep 2023 is a conference-abstract-style systematic review on the relationship between objective sleep duration and cognition plus brain-aging biomarkers in older adults. Cui 2026 is an observational cohort study in Parkinson's disease patients examining how depression and cognition mediate the relationship between REM sleep behaviour disorder (RBD) and activities of daily living (ADL) across 0.25, 0.50, and 0.75 standardised time points. The three sources therefore span the mechanistic-to-clinical continuum: a behavioural-program synthesis, an objective-sleep-duration synthesis, and a longitudinal mediation cohort.", "type": "claim"}, {"id": "claim_27", "text": "Mechanistically, the indirect-source evidence is mixed. Mohammadi 2021 shows that 12 months of regular physical activity altered the optical index of cerebral pulsatility, with effects on cognition reported at P < 0.001 and components at P > 0.1. Together these indirect studies suggest a biologically plausible chain linking duration exposures to neural and cognitive endpoints, but they do not converge on a single dose-response pattern.", "type": "claim"}, {"id": "claim_28", "text": "Preclinical and review-level evidence reinforces the duration–cognition link while sharpening the boundary conditions. These three reviews and cross-sectional studies together frame Cognition as a context-dependent, not uniformly positive, exposure class.", "type": "claim"}, {"id": "claim_29", "text": "Within-corpus tensions center on a single directness gap. Schrenk 2023 is a published randomized controlled trial protocol of an online guided physical activity training with cognition and gut–brain axis endpoints, with no empirical results reported in the available source; it should therefore be read as a planned study whose future findings would address the mechanism-to-clinic gap, not as a direct mechanistic/biomarker human evidence anchor. By contrast, Won 2023, Wang 2023, Tang 2024, Wang 2025, Zhang 2025, Escamilla 2026, and Mohammadi 2021 are all indirect, observational, or review-level evidence, so any apparent disagreement between Schrenk 2023 and these indirect sources is best interpreted as a maturity gap — protocol versus completed study — rather than a substantive directional conflict. Wang 2023, a structured corpus search and review of multi-task mode on cognition and lower limb function in frail older adults, contributes no p-values in the available source but supports dual-task training as a duration-structured intervention with cognitive and motor endpoints. Until Schrenk 2023 reports empirical data, the Cognition anti-aging case remains mechanistically plausible but anchored primarily in indirect, observational, and review-level human evidence, with the boundary conditions — including who benefits at which duration — yet to be established.", "type": "claim"}, {"id": "claim_30", "text": "Trial summary. Asteasu 2024 is a secondary analysis of a randomized clinical trial in acutely hospitalized older adults that modeled the dose-response relationship between exercise-session duration and functional and cognitive endpoints, with the acute clinical condition described as comparable across study groups (Asteasu 2024). The endpoint class is mechanistic/biomarker-adjacent, and the population is older adults receiving inpatient care. The trial design supports a direct, within-patient attribution of dose to outcome under controlled conditions.", "type": "claim"}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1093/geroni/igae053", "effect": "not extracted", "endpoint": "not extracted", "id": "source_1", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Dose-Response Relationship Between Exercise Duration and Enhanced Function and Cognition in Acutely Hospitalized Older Adults: A Secondary Analysis of a Randomized Clinical Trial", "type": "source", "url": "https://doi.org/10.1093/geroni/igae053", "year": 2024}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1038/s41598-025-24009-4", "effect": "not extracted", "endpoint": "not extracted", "id": "source_2", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Effectiveness of behavioural sleep programs for middle-aged adults on cognition and sleep and associated behaviour change techniques: a systematic review and meta-analysis", "type": "source", "url": "https://doi.org/10.1038/s41598-025-24009-4", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1007/s40520-019-01445-7", "effect": "not extracted", "endpoint": "not extracted", "id": "source_3", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Physical fitness in institutionalized older adults with dementia: association with cognition, functional capacity and quality of life", "type": "source", "url": "https://doi.org/10.1007/s40520-019-01445-7", "year": 2020}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1186/s11556-026-00404-2", "effect": "not extracted", "endpoint": "not extracted", "id": "source_4", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Optimal type and dose of exercise to improve cognitive function in healthy and pre-sarcopenic older adults: a bayesian network meta-analysis of randomized controlled trials", "type": "source", "url": "https://doi.org/10.1186/s11556-026-00404-2", "year": 2026}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1002/alz.71512", "effect": "not extracted", "endpoint": "not extracted", "id": "source_5", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Sleep and cognition in Hispanic/Latin American adults: A systematic review", "type": "source", "url": "https://doi.org/10.1002/alz.71512", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3233/ADR-220062", "effect": "not extracted", "endpoint": "not extracted", "id": "source_6", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Large-Scale Network Connectivity and Cognitive Function Changes After Exercise Training in Older Adults with Intact Cognition and Mild Cognitive Impairment", "type": "source", "url": "https://doi.org/10.3233/ADR-220062", "year": 2023}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/brainsci11060730", "effect": "not extracted", "endpoint": "not extracted", "id": "source_7", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Longitudinal Impact of Physical Activity on Brain Pulsatility Index and Cognition in Older Adults with Cardiovascular Risk Factors: A NIRS Study", "type": "source", "url": "https://doi.org/10.3390/brainsci11060730", "year": 2021}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fpsyt.2026.1776297", "effect": "not extracted", "endpoint": "not extracted", "id": "source_8", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Depression and cognition mediated rapid eye movement sleep behavior disorder to improve the activities of daily living in Parkinson’s disease patients", "type": "source", "url": "https://doi.org/10.3389/fpsyt.2026.1776297", "year": 2026}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1007/s40520-025-03233-y", "effect": "not extracted", "endpoint": "not extracted", "id": "source_9", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Meta-analysis of the effects of dance- and movement-based kinesthetic games on cognitive function in older adults with cognitive impairment (CI) under different intervention periods", "type": "source", "url": "https://doi.org/10.1007/s40520-025-03233-y", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1093/braincomms/fcae144", "effect": "not extracted", "endpoint": "not extracted", "id": "source_10", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Association of objective sleep duration with cognition and brain aging biomarkers in older adults", "type": "source", "url": "https://doi.org/10.1093/braincomms/fcae144", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fnut.2025.1655601", "effect": "not extracted", "endpoint": "not extracted", "id": "source_11", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Association of lifestyle, dietary pattern, and liver function with cognition in older adults: findings from a cross-sectional study", "type": "source", "url": "https://doi.org/10.3389/fnut.2025.1655601", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/healthcare11233012", "effect": "not extracted", "endpoint": "not extracted", "id": "source_12", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Effects of Multi-Task Mode on Cognition and Lower Limb Function in Frail Older Adults: A Systematic Search and Review", "type": "source", "url": "https://doi.org/10.3390/healthcare11233012", "year": 2023}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1002/alz.075234", "effect": "not extracted", "endpoint": "not extracted", "id": "source_13", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Association of Objective Sleep Duration with Cognition and Brain Aging Biomarkers in Older Adults", "type": "source", "url": "https://doi.org/10.1002/alz.075234", "year": 2023}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fnagi.2023.1254194", "effect": "not extracted", "endpoint": "not extracted", "id": "source_14", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Impact of an online guided physical activity training on cognition and gut-brain axis interactions in older adults: protocol of a randomized controlled trial", "type": "source", "url": "https://doi.org/10.3389/fnagi.2023.1254194", "year": 2023}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_15", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**Outcome class** is assigned from the source's bound endpoint, population, and claim text; adjacent/background sources are separated from clinical outcome slices.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_16", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**Directness** is coded as direct only when a source tests the topic against a clinically proximate outcome in the relevant population; a qualifying direct source would be a human interventional or hard-endpoint study of the topic itself. Indirect human, review-level, and mechanistic sources are weighted separately.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_17", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**Directional signal** is counted within the assigned outcome class only. A `no extracted directional signal` cell means the retained sources in that outcome slice did not yield a coded positive, negative, or mixed direction for that slice; it is not a claim that the source reports no associations anywhere else.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_18", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**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.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.1371/journal.pmed.0020124", "effect": "not extracted", "endpoint": "not extracted", "id": "source_19", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Ioannidis 2005", "type": "source", "url": "https://doi.org/10.1371/journal.pmed.0020124", "year": null}], "publication_id": "ff0b0ca6-f6d9-4aba-9607-9ac47683763a", "screening": {"excluded": 0, "exclusion_reasons": ["No PRISMA full-text exclusion-stage filter was applied."], "flow": ["identified", "screened", "excluded_with_reasons", "included"], "identified": 14, "included": 14, "included_or_retained": 14, "screened": 14, "wording": "14 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit."}}

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