# Longitudinal association between sleep and Alzheimer's pathology

## TL;DR

Irregular sleep patterns in older adults are linked to early signs of Alzheimer's disease, suggesting sleep could be a target for prevention.

## Contribution

This study identifies sleep variability as a novel early marker of Alzheimer's pathology in cognitively unimpaired individuals.

## Key findings

- Greater sleep variability is associated with higher amyloid and tau burden in preclinical Alzheimer's.
- Variability in sleep efficiency predicts faster amyloid accumulation over time.
- Sleep irregularity may serve as a sensitive marker of preclinical Alzheimer's pathophysiology.

## Abstract

Since sleep disturbance is a modifiable risk factor for Alzheimer's disease (AD), we tested associations between sleep and AD pathology in cognitively unimpaired (CU) persons.

We included 223 participants from the PREVENT‐AD cohort with self‐reported measures of sleep, objective actigraphy measures of sleep, and positron emission tomography (PET) scans for AD pathology quantification. Repeated PET scans (mean follow‐up: 4.31 ± 0.55 years) were available for 103 participants. We conducted robust linear models (RLM) for cross‐sectional analyses and RLMs using the annual change in AD pathology for longitudinal analyses.

All actigraphy‐based sleep variability measures were associated with tau burden (duration: β = 0.121 [95% confidence interval {CI} = 0.010; 0.232], p = 0.034; efficiency: 0.122 [0.010; 0.235], 0.033; fragmentation: 0.115 [0.010; 0.221], 0.033). Greater variability in sleep fragmentation was also associated with amyloid burden (0.074 [0.008; 0.140], 0.028), and variability in sleep efficiency portended amyloid burden and faster accumulation over time (0.075 [0.009; 0.141], 0.026; 0.164 [0.008; 0.320], 0.039; respectively).

Irregularity in sleep patterns is associated with higher pathological burden and faster amyloid accumulation.

Greater day‐to‐day variability in actigraphy‐based sleep measures was associated with higher amyloid and tau burden in cognitively unimpaired older adults at risk for Alzheimer's disease (AD).Greater day‐to‐day sleep variability—particularly variability in sleep efficiency—was also associated with faster amyloid accumulation over time.Sleep variability may serve as an early and sensitive marker of preclinical AD pathophysiology, highlighting its potential as a target for preventive interventions.

Greater day‐to‐day variability in actigraphy‐based sleep measures was associated with higher amyloid and tau burden in cognitively unimpaired older adults at risk for Alzheimer's disease (AD).

Greater day‐to‐day sleep variability—particularly variability in sleep efficiency—was also associated with faster amyloid accumulation over time.

Sleep variability may serve as an early and sensitive marker of preclinical AD pathophysiology, highlighting its potential as a target for preventive interventions.