Obstructive sleep apnea (OSA) is one of the most common sleep disorders in the aging population. While the negative effect of OSA on cognitive aging is widely known, little is known about how OSA interacts with Alzheimer’s disease (AD) risk factors to modify the course of cognitive performance changes across midlife and later life. The current study examined the interaction between OSA and apolipoprotein-e4 (APOE4), the largest known genetic factor of AD, on cognitive changes across 4 years using a community-based adult sample.

Study sample included 2,286 individuals from the Korean Genome and Epidemiology Study (KoGES) (mean age 58.8 (SD 6.9) at baseline, 48.2% female) who were dementia-free and had both polysomnography and neuropsychological test data at the baseline examination (Years 2011-2014). Follow-up examinations were conducted during years 2015-2018. Participants underwent overnight polysomnography at baseline, and the presence of OSA was determined by the apnea-hypopnea index of 15. Cognitive outcomes included measures of verbal and visual memory (Logical Memory and Visual Reproductions) along with measures of frontal network functioning, such as attention and executive functions (Trail Making Tests A and B, Digit Symbol, and Stroop Word and Color Word tests). The interaction between OSA and apolipoprotein-e4 genotype (APOE4) on cognitive outcomes was evaluated using the linear regressions, controlling for age, sex, education, body mass index, cardiovascular diseases, smoking, alcohol consumption, sedatives/hypnotics use, and depressive symptoms (using the Beck Depression Inventory [BDI]).

The presence of OSA at baseline was not associated with changes in cognitive outcomes over the 4-year follow-up period. However, examining interaction terms between OSA and APOE status indicated that OSA significantly interacted with APOE4 on the changes in verbal learning and memory performance scores, namely the Logical Memory-Immediate Recall (F=3.9, P = 0.02) and Logical Memory-Delayed Recall (F=4.81, P = 0.008). Specifically, in individuals with OSA, being APOE4 carrier was associated with a faster decline in both measures, compared with non-APOE4 carriers.

Our findings indicate that the presence of OSA during middle adulthood and early older adulthood could lead to a faster decline in verbal learning and memory in APOE4 carriers. Therefore, early detection and treatment of OSA (e.g., continuous positive airway pressure [CPAP]) may help reduce the risk of developing memory impairment in individuals with higher genetic risk of Alzheimer’s disease.