Prolonged sleep duration as a marker of early neurodegeneration predicting incident dementia

Objective: To evaluate the association between sleep duration and the risk of incident dementia and brain aging. Methods: Self-reported total hours of sleep were examined in the Framingham Heart Study (n = 2,457, mean age 72 +/- 6 years, 57% women) as a 3-level variable:,6 hours (short), 6-9 hours (reference), and >9 hours (long), and was related to the risk of incident dementia over 10 years, and cross-sectionally to total cerebral brain volume (TCBV) and cognitive performance. Results: We observed 234 cases of all-cause dementia over 10 years of follow-up. In multivariable analyses, prolonged sleep duration was associated with an increased risk of incident dementia (hazard ratio [HR] 2.01; 95% confidence interval [CI] 1.24-3.26). These findings were driven by persons with baseline mild cognitive impairment (HR 2.83; 95% CI 1.06-7.55) and persons without a high school degree (HR 6.05; 95% CI 3.00-12.18). Transitioning to sleeping >9 hours over a mean period of 13 years before baseline was associated with an increased risk of all-cause dementia (HR 2.43; 95% CI 1.44-4.11) and clinical Alzheimer disease (HR 2.20; 95% CI 1.174.13). Relative to sleeping 6-9 hours, long sleep duration was also associated cross-sectionally with smaller TCBV (beta +/- SE, -1.08 +/- 0.41 mean units of TCBV difference) and poorer executive function (beta +/- SE, - 0.41 +/- 0.13 SD units of Trail Making Test B minus A score difference). Conclusions: Prolonged sleep duration may be a marker of early neurodegeneration and hence a useful clinical tool to identify those at a higher risk of progressing to clinical dementia within 10 years.