Association of Excessive Daytime Sleepiness With Long-Term Incident Dementia: The Role of β-Amyloid and White Matter Injury.

INTRODUCTION

Excessive daytime sleepiness (EDS) is common in community-dwelling older adults, but its association with long-term incident dementia remains unclear. The roles of Alzheimer's disease (AD) pathology and vascular-related white matter injury in this association were merely studied.

METHODS

We included 617 dementia-free participants from the Shanghai Aging Study with up to 10 years of follow-up. At baseline, EDS was assessed with the Epworth Sleepiness Scale (ESS) and plasma phosphorylated tau (p-tau)217 was measured using a single-molecule immune-array assay. Cognitive decline was evaluated using the Mini-Mental State Examination (MMSE), and incident dementia was determined by expert consensus during follow-up. A magnetic resonance imaging marker of white matter injury (peak width of skeletonized mean diffusivity [PSMD]) was derived from diffusion tensor imaging, and gray matter volume was assessed from T1-weighted imaging in a subcohort.

RESULTS

At baseline, 66 participants (10.7%) had EDS and showed lower MMSE scores. EDS was associated with a higher risk of incident dementia (hazard ratio [HR] 2.06, 95% confidence interval [CI] 1.09-3.92), especially among individuals with low p-tau217 (HR 4.94, 95% CI 1.75-13.93) independent of sleep disturbance after adjusting for age, sex, and education. Higher ESS was related to AD pathology-dependent patterns of brain atrophy and to higher PSMD. PSMD modified the associations between EDS and cognitive decline, and incident dementia. Participants with both high PSMD and EDS showed the highest dementia risk.

DISCUSSION: EDS may help identify older adults with low AD biomarker burden who are at increased risk of dementia, independent of nocturnal sleep disturbance. White matter injury may contribute to this risk, supporting a vascular vulnerability pathway.