Witnessed Apneas During Sleep are Associated with Elevated Tau-PET Signal in the Entorhinal Cortex in Cognitively Unimpaired Elderly (P3.6-021)

Objective: To assess whether self- or informant-reported apneas during sleep (witnessed apneas) in cognitively unimpaired (CU) elderly are associated with higher levels of tau. Background: Recent evidence has supported an association between sleep disruption, particularly obstructive sleep apnea (OSA), and increased risk for dementia. However, the underlying pathological processes remain poorly understood. Design/Methods: From the population-based Mayo Clinic Study of Aging, we identified 288 CU elderly aged >=65 years with both Tau-PET and Amyloid-PET scans and who had completed a questionnaire assessing the participants and their bed partners for witnessed apneas during sleep. In this cross-sectional analysis, we selected the entorhinal cortex (ERC) as our region of interest because it is highly susceptible to tau accumulation, and the cerebellum crus as a reference region (standardized uptake value ratio, SUVR). We fit a linear model to assess the association between ERC tau and witnessed apneas, while controlling for age, sex, years of education, body mass index, hypertension, hyperlipidemia, diabetes, reduced sleep, excessive daytime sleepiness, and global amyloid. Results: 43 participants (15%) had witnessed apneas during sleep. Witnessed apneas were significantly associated with tau in the ERC. Our model estimated a 0.049 elevation (95%CI 0.011 – 0.087, p=.012) in the ERC tau SUVR, after controlling for multiple confounders. Conclusions: We identified a significant association between witnessed apneas during sleep and elevated Tau PET signal in the ERC. This observation raises the possibility that sleep apnea affects tau accumulation, which is one of the main biomarkers of Alzheimer’s disease. Longitudinal observations will be necessary to determine direction of causality. Disclosure: Dr. Carvalho has nothing to disclose. Dr. St. Louis has nothing to disclose. Dr. Boeve has received research support from Biogen. Dr. Schwarz has nothing to disclose. Dr. Przybelski has nothing to disclose. Dr. Knopman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Washington University for the DIAN study. Dr. Knopman has received research support from Biogen Pharmaceuticals and Lilly Pharmaceuticals. Dr. Lowe has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer Schering Pharma, Piramal Life Sciences. Dr. Lowe has received research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals. Dr. Mielke has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly and Lysosomal Therapeutics, Inc. Dr. Mielke has received research support from Biogen, Roche, and Lundbeck. Dr. Reddy has nothing to disclose. Dr. Petersen has nothing to disclose. Dr. Jack has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lily. Dr. Vemuri has nothing to disclose.