OBSTRUCTIVE SLEEP APNEA-DEPENDENT RACIAL/ETHNIC AND SEX-SPECIFIC MECHANISMS UNDERLYING ALZHEIMER'S DISEASE RISK: A RETROSPECTIVE COHORT ANALYSIS OF IN-LAB PSG SLEEP STUDY DATA

Abstract Introduction We examined race and sex-specific biologic mechanisms of the relationship between obstructive sleep apnea (OSA) and incident AD. Methods Retrospective cohort analysis utilizing in-lab PSG sleep study data conducted among older adults between 2001 and 2005. OSA was defined using AHI4%. Participants had no history of cognitive decline or AD at baseline and included 663 (284 Non-Hispanic White (NHW), 207 Black/African-American (AA) and 172 Hispanic) OSA-patients matched on age, sex, race, BMI, 1:1 ratio to 663 (unexposed cohort I from sleep clinic) and 1:4 ratio to 2652 (unexposed cohort II from non-sleep clinics) non-OSA individuals. Incident AD was assessed annually from 2001-2013 with ICD-9-CM code 331.0. Adjusted cox proportional hazard regression models examined race and sex-specific biologic mechanisms including hypoxia, fragmentation and duration measures of OSA and AD risk. Results Of the 3,978 participants, 2,148 (54%) were women. Mean age at baseline was 72.6 (7.3) years. Over a mean follow-up time of 8.6 (1.4) years, 358 (9%) individuals (212 female) developed AD (119 NHW, 134 AAs, and 105 Hispanics). Relative to non-OSA individuals, OSA-patients had a higher risk of incident AD, with AAs and females showing stronger risk estimates (aHR: 2.24, 1.83, and 1.73, P <.001 for all, for AAs, Hispanics and NHW respectively; and aHR: 2.38, and 1.37, P <.001 for all, for female and male respectively). Measures of hypoxia, sleep fragmentation and sleep duration were associated with increase AD risk (P <.01 for all). Relative to NHW, AAs and Hispanics demonstrated up to 20% stronger effects/estimates on hypoxia and sleep duration measures. Relative to males, females demonstrated up to 25% stronger effects/estimates on sleep fragmentation measures, and 15% weaker effects/estimates on hypoxia measures (P <.01 for all). Conclusion Among OSA-patients, mechanisms related to hypoxia, sleep fragmentation and duration measures increase AD risk and may underlie race/ethnicity and sex disparities in AD. Support NIH/NIA/NHLBI (L30-AG064670, CIRAD P30AG059303 Pilot, T32HL129953, R01HL118624, R21AG049348, R21AG055002, R01AG056031, R01AG022374, R21AG059179, R01AG056682, R01AG056531, K07AG05268503, K23HL125939)