Sleep Medicine · Jul 25, 2026

Trajectories of sleep disturbance in older adults and their associations with clinical and pathological outcomes in AD: A longitudinal study

By Sui JZ, Yin WW, Yu HH et al.

BACKGROUND: Sleep disturbance is a core feature of affective and neurodegenerative disorders. This study tracks long-term sleep disturbance trajectories and their links to incident Alzheimer's disease (AD) and longitudinal clinical and pathological changes. METHODS: A total of 774 non-demented participants from the ADNI cohort were included. Sleep disturbance (NPI sleep item) trajectories over 8 years were identified via group-based trajectory modeling. Cox proportional hazards regression was used to estimate the risk of incident AD. Linear mixed-effects models were used to assess longitudinal changes in cognition, structural magnetic resonance imaging, amyloid-β positron emission tomography (Aβ-PET), fluorodeoxyglucose (FDG)-PET, and cerebrospinal fluid (CSF) biomarkers. RESULTS: Three trajectories emerged: "Low-stable" (37.2%), "High-peaked" (21.0%), and "Moderate-increasing" (41.8%). Compared to those without sleep disturbance, a significantly elevated risk of incident AD was associated with "High-peaked" (hazard ratio [HR] = 3.28; 95% confidence interval [CI] = 1.89-5.70; p < 0.001) and "Moderate-increasing" trajectories (HR = 2.13; 95% CI = 1.28-3.53; p = 0.003) but not with the "Low-stable" trajectory (p = 0.888). Participants with "High-peaked" trajectory exhibited faster declines in cognition (MMSE, memory, executive function) (p < 0.050) and a steeper reduction in CSF Aβ₁₋₄₂ levels (p = 0.038) than those with non-sleep disturbance. However, there were no significant differences between groups in the rates of hippocampal, entorhinal, or middle temporal atrophy, global Aβ-PET burden, or FDG-PET changes (p > 0.050). CONCLUSIONS: "High-peaked" and "Moderate-increasing" sleep trajectories predict higher AD risk, faster cognitive decline, and faster Aβ₁₋₄₂ reduction. Long-term monitoring of sleep behaviors is essential for identifying and stratifying individuals at high risk for AD.

doi.org/10.1016/j.sleep.2026.109168PubMed 42542107Populations