0560 Associations of Late Midlife Sleep-Disordered Breathing with Late-Life Brain Amyloid Deposition

Abstract Introduction Sleep-disordered breathing (SDB) is a potentially modifiable risk factor for the prevention of dementia, of which Alzheimer’s disease (AD) is the most common cause. However, there is a lack of longitudinal evidence relating SDB to AD pathology 20 years later. We examined the association between late-midlife SDB and late-life brain β-amyloid (Aβ) deposition—a hallmark of AD—assessed approximately 23 years later. Methods The Atherosclerosis Risk in Communities (ARIC) Study is an ongoing prospective cohort study initiated in 1987. Participants at two ARIC sites (Washington County, Maryland; Minneapolis, Minnesota) with primarily White participants also completed polysomnography (PSG) in the Sleep Heart Health Study (SHHS) in 1995-98. SDB measures included apnea-hypopnea index (AHI; number of apneas + hypopneas with ≥3% oxygen desaturation/hour of sleep), arousal index, and percentage of total sleep time in apnea, in hypopnea, and with oxygen saturation 90%. A subset of participants completed florbetapir positron emission tomography (PET) scans through several ARIC ancillary studies (2011-2025 including the ARIC Sleep-PET study). We defined Aβ deposition as a global standardized uptake value ratio (SUVR) 1.2 (vs. SUVR ≤1.2). We used Poisson regression with robust standard errors to estimate relative risk (RR) of Aβ deposition by SDB, adjusting for demographics and vascular risk factors, and applied inverse probability attrition weighting to account for selective drop-out. Results Among 186 dementia-free participants (mean age=59 years at PSG and 82 years at PET scan, 58% female, 98% White), every 10% increase in total sleep time in hypopnea was associated with higher risk of Aβ deposition (RR=1.40, 95% confidence interval CI: 1.03, 1.91). When compared to no SDB (AHI 5), moderate to severe SDB (AHI ≥15) was associated with elevated Aβ deposition (RR=2.36, 95% CI: 1.22, 4.57); mild SDB (AHI 5 to 15) was not (RR=1.05, 95% CI: 0.53, 2.07). Conclusion SDB in late midlife was associated with greater risk of Aβ deposition approximately 23 years later. SDB may play a role in the early stages of AD pathogenesis. Future longitudinal studies are needed to optimize strategies for screening and treating SDB for dementia prevention. Support (if any) Supported in part by RF1AG050745.