Sleep Fragmentation and the Risk of Incident Alzheimer's Disease and Cognitive Decline in Older Persons

Objective: Cross-sectional studies suggest that sleep fragmentation is associated with cognitive performance in older adults. We tested the hypothesis that sleep fragmentation is associated with incident Alzheimer's disease (AD) and the rate of cognitive decline in older adults. Design: Prospective cohort study. Setting: Community-based Participants: 737 community dwelling older adults without dementia. Measurements and Results: Sleep fragmentation was quantified from up to 10 consecutive days of actigraphy. Subjects underwent annual evaluation for AD with 19 neuropsychological tests. Over a follow-up period of up to 6 years (mean 3.3 years), 97 individuals developed AD. In a Cox proportional hazards model controlling for age, sex, and education, a higher level of sleep fragmentation was associated with an increased risk of AD (HR = 1.22, 95%CI 1.03-1.44, P = 0.02 per 1SD increase in sleep fragmentation). An individual with high sleep fragmentation (90th percentile) had a 1.5-fold risk of developing AD as compared with someone with low sleep fragmentation (10th percentile). The association of sleep fragmentation with incident AD did not vary along demographic lines and was unchanged after controlling for potential confounders including total daily rest time, chronic medical conditions, and the use of common medications which can affect sleep. In a linear mixed effect analysis, a 0.01 unit increase in sleep fragmentation was associated with a 22% increase in the annual rate of cognitive decline relative to the average rate of decline in the cohort (Estimate = -0.016, SE = 0.007, P = 0.03). Conclusions: Sleep fragmentation in older adults is associated with incident AD and the rate of cognitive decline.