Irregularity in sleep patterns is associated with higher pathological burden and faster amyloid accumulation in cognitively unimpaired persons at risk for Alzheimer's disease.
Key Findings
Results
All actigraphy-based sleep variability measures were associated with tau burden in cognitively unimpaired individuals.
Variability in sleep duration was associated with tau burden (β = 0.121, 95% CI = 0.010–0.232, p = 0.034)
Variability in sleep efficiency was associated with tau burden (β = 0.122, 95% CI = 0.010–0.235, p = 0.033)
Variability in sleep fragmentation was associated with tau burden (β = 0.115, 95% CI = 0.010–0.221, p = 0.033)
Analyses were conducted using robust linear models (RLM) for cross-sectional analyses
Sample included 223 participants from the PREVENT-AD cohort with objective actigraphy measures and PET scans
Results
Greater variability in sleep fragmentation was associated with amyloid burden in cognitively unimpaired individuals.
β = 0.074 (95% CI = 0.008–0.140, p = 0.028)
This cross-sectional association was identified using robust linear models
Participants were cognitively unimpaired members of the PREVENT-AD cohort
Results
Variability in sleep efficiency was associated with both cross-sectional amyloid burden and faster amyloid accumulation over time.
Cross-sectional association between sleep efficiency variability and amyloid burden: β = 0.075 (95% CI = 0.009–0.141, p = 0.026)
Longitudinal association between sleep efficiency variability and faster amyloid accumulation: β = 0.164 (95% CI = 0.008–0.320, p = 0.039)
Longitudinal analyses used RLMs with annual change in AD pathology as the outcome
103 participants had repeated PET scans with a mean follow-up of 4.31 ± 0.55 years
Methods
The study included both self-reported and objective actigraphy-based sleep measures alongside PET-quantified AD pathology in a cognitively unimpaired cohort.
223 participants from the PREVENT-AD cohort were included in cross-sectional analyses
103 participants had repeated PET scans available for longitudinal analyses
Mean follow-up for longitudinal analyses was 4.31 ± 0.55 years
Sleep measures included self-reported measures and objective actigraphy-derived measures
AD pathology was quantified using positron emission tomography (PET) scans for both amyloid and tau
Background
Sleep disturbance, particularly irregularity in sleep patterns, is identified as a modifiable risk factor associated with Alzheimer's disease pathology in cognitively unimpaired persons.
The study focuses specifically on sleep variability metrics (duration variability, efficiency variability, fragmentation variability) rather than average sleep characteristics
Associations were found for both amyloid and tau pathology, the two hallmark proteins of Alzheimer's disease
Participants were cognitively unimpaired, suggesting these associations precede clinical symptoms
The PREVENT-AD cohort is designed to study preclinical Alzheimer's disease risk
What This Means
This research suggests that irregularity in sleep patterns — not just how much or how well someone sleeps on average, but how much those patterns vary from night to night — is linked to greater accumulation of Alzheimer's-related proteins in the brain. The study followed 223 cognitively normal adults (people with no signs of memory problems) from the PREVENT-AD cohort, measuring their sleep objectively using wrist-worn actigraphy devices and scanning their brains using PET imaging to detect amyloid and tau, the two hallmark proteins associated with Alzheimer's disease. People whose sleep duration, efficiency, and fragmentation varied more from night to night had higher levels of tau in their brains, and those with more variable sleep efficiency also had higher amyloid levels.
Particularly notable is the longitudinal finding: among the 103 participants who had two brain scans approximately 4 years apart, those with more variable sleep efficiency showed faster accumulation of amyloid over time. This suggests that irregular sleep may not just be a marker of existing disease but could be contributing to the ongoing buildup of Alzheimer's pathology even before any cognitive symptoms appear.
This research matters because sleep patterns are potentially modifiable — unlike genetic risk factors, they can be changed. The findings suggest that stabilizing sleep patterns (reducing night-to-night variability) could be a worthwhile target for strategies aimed at reducing Alzheimer's disease risk, though further research is needed to determine whether improving sleep regularity can actually slow the accumulation of these harmful brain proteins.
Mohammediyan B, Baril A, Fajardo Valdez A, St-Onge F, Pichet Binette A, Carrier J, et al.. (2026). Longitudinal association between sleep and Alzheimer's pathology.. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.71228