Association of Sleep Disordered Breathing and Cognitive Deficit in APOE ε4 Carriers

Study Objectives: The aim of the study was to determine whether apolipoprotein E epsilon 4 genotype (APOE4) modifies the association of sleep disordered breathing (SDB) with cognitive function in a middle-aged population. Design: Cross-sectional analysis of a community-dwelling cohort. Settings: Sleep laboratory at the Clinical Research Unit of the University of Wisconsin Hospitals and Clinics. Participants: There were 755 adults from the Wisconsin Sleep Cohort who provided a total of 1,843 polysomnography and cognitive evaluations (most participants were assessed multiple times at approximately 4-y intervals); 56% males, average age 53.9 years (range 30-81 years). Interventions: None. Measurement and Results: In-laboratory overnight polysomnography was used to assess SDB. Cognition was evaluated by a battery of six neurocognitive tests assessing memory and learning, attention, executive function, and psychomotor efficiency. The APOE4 genotype (epsilon 3/epsilon 4 or epsilon 4/epsilon 4) was identified in 200 participants. Data were analyzed using linear mixed-effects models, accounting for multiple observations per participant. Cognitive test scores were regressed on SDB categories (AHI < 5, 5 <= AHI >= 15, AHI = 15); APOE4 and their interaction; and age, education, sex, and body mass index. There was no statistically significant association between SDB and cognitive performance among APOE4-negative individuals. However, in APOE4-positive individuals, those with AHI >= 15 had significantly worse performance on the Auditory Verbal Learning Test and the Controlled Oral Word Association Test. Conclusions: In APOE4-positive individuals, moderate to severe sleep disordered breathing (AHI >= 15) was associated with poorer performance on cognitive tests that require both memory and executive function engagement.