AbstractBackgroundAPOE alleles are associated with cognitive‐decline and Alzheimer’s disease in Whites. We examined the effect of APOE‐genotype on the association between sleep disturbance (SD) and cognition across racial/ethnic groups.MethodWe conducted a cross‐sectional analysis of baseline data on 10,254 (i.e., 7900 non‐Hispanic Whites, 1428 Black/African‐Americans, 627 Hispanics and 299 Asians) cognitive‐normal subjects from the National Alzheimer’s Coordinating Center Uniform Dataset. We characterized SD using an item on the Neuropsychiatric Inventory‐Questionnaire. Generalized linear models examined SD‐group differences (i.e., SD vs. no SD) on psychometric tests performance between‐and‐within racial categories. The interactive associations of APOE genotype, SD, and race on psychometric tests performance was also examined. All models included age, sex, education, hypertension, and diabetes.ResultOverall, the mean (sd) age was 71.1 (10.3) years and education was 15.7 (3.0) years. Prevalence of SD was 10% (Whites), 6.1% (Blacks), 18.2% (Hispanics), and 7.4% (Asians). SD subjects were at increased risk for worse psychometric scores in: executive, and language domains (p < 0.02 for all) among Whites; language domain (p = 0.001) among Blacks; memory, executive, and language domains (p ≤0.05 for all) among Hispanics; and visuospatial memory domain (p ≤0.001) among Asians. The interactive associations of APOE genotype, SD, and race on psychometric tests performance were significant (p ≤0.001 for all). Within racial groups, only Hispanic SD subjects with 1 or 2 APOE ε4 alleles were at increased risk for worse psychometric scores in memory, executive function, visuospatial, attention, processing speed and language domains (p ≤0.001 for all). Compared to Whites and Asians, Hispanic and Black SD subjects were at increased risk for worse psychometric scores across all domains (p ≤0.001 for all), regardless of APOE‐ε4 status.ConclusionIn this sample of cognitive‐normal older‐adults, SD subjects were at increased risk for worse psychometric scores in specific cognitive domains that varied by race/ethnicity. Hispanic and Black SD subjects were at increased risk for worse psychometric scores regardless of APOE‐ε4 status. APOE‐ε4 effect on SD‐cognition association worsened psychometric scores and occurred only within Hispanics. These findings suggest that APOE‐ε4 interacts with sleep to effect varying cognitive domain outcomes within‐and‐between racial/ethnic groups.