Sleep spindles and slow oscillations predict amyloid beta, tau pathology, and cognitive decline in persons with mild to moderate Alzheimer's Disease.”
Bibliographic record
Abstract
BACKGROUND: Sleep plays vital roles in brain-health and cognition, including regulating clearance of β-amyloid (Aβ) and tau proteins that hallmark Alzheimer's disease (AD). Changes in sleep physiology can predate cognitive symptoms by decades in AD, but it remains unclear which sleep characteristics predict cognitive and neurodegenerative changes after AD onset. METHODS: Using data from a prospective cohort study of mild-to-moderate AD (n = 60, 30 female, mean age 74.7) in Lleida, Spain, we analysed non-rapid eye-movement sleep spindles and slow oscillations (SO) at baseline and their associations with baseline amyloid-beta and tau, and with cognition from baseline to three-years follow-up. Participants underwent polysomnography (PSG), blood and cerebrospinal fluid draws for amyloid and tau at baseline, and neuropsychological assessment at baseline, 12, 24 and 36 months with the Mini-Mental Status Examination (MMSE), California verbal learning test (CVLT), Rey-Osterrieth Complex Figure Test (ROCF), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Spindle and SO detection were performed using in-house, open-source software packages developed at Concordia University. Associations between SO and spindle and SO duration, density, power, amplitude, AD biomarkers, and cognition from baseline to 36 months were investigated with false discovery rate-adjusted generalised linear models controlling for age, sex, apnoea-hypopnea index. RESULTS: We found previously unreported associations between spindle and SO activity, biomarkers, and cognition in persons with AD. Higher spindle and SO density, duration, amplitude and power predicted significant changes in amyloid-beta 42 (β= 69.3 p = 0.001), phosphorylated (pTau-181) (β= 7.92, p = 0.001) and total-tau, and tau/Aβ42 (β= -0.52, p = 0.001), clinically and statistically significantly lower Alzheimer's Disease Assessment Scale Cognitive Subscale (better cognitive performance) (β= -9.0, p = 0.001) and higher Mini-Mental State Examination scores (better cognitive performance) (β= 15.2, p = 0.01) from baseline to 36-months, and significant changes in verbal and visual memory on the ROCF and CVLT. Spindles and SO activity also mediated the effect of pTau181/aβ42 on cognition (41-81%), while pTau181/aβ42 moderated the effect of spindles and SO on cognition. CONCLUSIONS: Our findings demonstrate that spindle and SO activity during sleep constitute predictive and non-invasive biomarkers of neurodegeneration and cognition in AD patients and novel treatment targets for delaying cognitive decline and AD progression.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".