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 (ε3/ε4 or ε4/ ε4) 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.
Keywords: APOE4; cognitive deficit; sleep apnea.