Abstract
Objective: To test the hypothesis that baseline excessive daytime sleepiness (EDS) predicts subsequent longitudinal pattern of β-amyloid accumulation in non-demented community dwelling elderly.
Background: Aging is associated with increased daytime sleepiness, which has been associated with cognitive decline in the elderly. However, it remains unclear whether EDS is associated with Alzheimer’s disease (AD) pathology, particularly β-amyloid accumulation, given that sleep appears to promote β-amyloid clearance.
Design/Methods: From the population-based sample of Mayo Clinic Study of Aging, we identified 283 non-demented individuals aged 70 and older who had at least two serial PiB-PET scans and completed sleep questionnaires. EDS was defined as Epworth Sleepiness Scale score ≥10. Multiple linear regression models were fit in six AD-related regions (orbitofrontal, prefrontal, anterior cingulate, cingulate-precuneus, temporal, and parietal) to explore whether EDS at baseline predicted variability in amyloid accumulation between two serial scans, while controlling for baseline age, sex, APOE4, education, regional PiB positivity (SUVR ≥ 1.4), physical activity, cardiovascular comorbidities (obesity, hypertension, hyperlipidemia, diabetes), reduced sleep duration, respiratory symptoms during sleep (snoring and/or witnessed apneas), depression and interval between scans.
Results: Baseline EDS was significantly associated with increased β-amyloid accumulation in the orbitofrontal, anterior cingulate and cingulate/precuneus regions when the models included all subjects. However, the strength of the associations was stronger in PiB-positive areas. EDS predicted further increased β-amyloid accumulation in the anterior cingulate (0.06, 95%CI: 0.02–0.1, p=0.007), cingulate/precuneus (0.076; 95%CI: 0.03–0.12, p=0.002), and parietal cortex (0.058, 95%CI: 0.01–0.11, p=0.03) in the subset of subjects who were amyloid positive at baseline in these regions.
Conclusions: EDS in non-demented elderly was associated with an increased rate of β-amyloid accumulation particularly in areas associated with the default mode network (DMN). DMN regions are vulnerable to increased amyloid accumulation, suggesting that treating sleep disorders underlying EDS may be a targetable pathway towards prevention of β-amyloid accumulation in these areas.
Study Supported by: NIH
Disclosure: Dr. Carvalho has nothing to disclose. Dr. St. Louis has received personal compensation for activities with Axovant, Inc. and Inspire, Inc. Dr. Knopman has received personal compensation for activities with Lundbeck Pharmaceuticals.Dr. Knopman has received research support from Lilly Pharmaceuticals, Biogen and TauRX. Dr. Boeve has received research support from GE Healthcare, FORUM Pharmaceuticals, C2N Diagnostics and Axovant. Dr. Lowe received personal compensation for activities with Bayer Pharmaceuticals as a consultant. Dr. Roberts has nothing to disclose. Dr. Mielke has received personal compensation for activities with Lysosomal Therapeutics, Inc. as a consultant. Dr. Mielke has received research support from Biogen. Dr. Przybelski has nothing to disclose. Dr. Petersen received personal compensation for activities with Merck, Roche, Genentech, Biogen, and Eli Lilly and Co. Dr. Jack has received personal compensation for activities with Janssen Research & Development, LLC by providing consulting services. Dr. Jack has received research support from the National Institutes of Health (R01-AG011378, RO1-AG041851, RO1-AG037551. Dr. Vemuri has nothing to disclose.
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