Day-to-day sleep variability with Alzheimer's biomarkers in at-risk elderly

Alzheimers Dement (Amst). 2024 Feb 16;16(1):e12521. doi: 10.1002/dad2.12521. eCollection 2024 Jan-Mar.


Introduction: Measuring day-to-day sleep variability might reveal unstable sleep-wake cycles reflecting neurodegenerative processes. We evaluated the association between Alzheimer's disease (AD) fluid biomarkers with day-to-day sleep variability.

Methods: In the PREVENT-AD cohort, 203 dementia-free participants (age: 68.3 ± 5.4; 78 males) with a parental history of sporadic AD were tested with actigraphy and fluid biomarkers. Day-to-day variability (standard deviations over a week) was assessed for sleep midpoint, duration, efficiency, and nighttime activity count.

Results: Lower cerebrospinal fluid (CSF) ApoE, higher CSF p-tau181/amyloid-β (Aβ)42, and higher plasma p-tau231/Aβ42 were associated with higher variability of sleep midpoint, sleep duration, and/or activity count. The associations between fluid biomarkers with greater sleep duration variability were especially observed in those that carried the APOE4 allele, mild cognitive impairment converters, or those with gray matter atrophy.

Discussion: Day-to-day sleep variability were associated with biomarkers of AD in at-risk individuals, suggesting that unstable sleep promotes neurodegeneration or, conversely, that AD neuropathology disrupts sleep-wake cycles.

Keywords: APOE ε4; accelerometry; amyloid; apolipoprotein; atrophy; bedtime; blood; blood‐brain barrier; dementia; gray matter volume; mild cognitive impairment; phosphorylated; p‐tau181; p‐tau231; tau.