Relationship Between Apolipoprotein E Genotypes, Unhealthy Weight Status, and Cognitive Impairment in Older Adults of Predominantly African Descent

<b>Background:</b> Apolipoprotein E4 (<i>APOE4</i>) represents a major genetic risk factor for Alzheimer's disease. <b>Objectives:</b> We aimed to analyze the relationship between cognitive impairment (CI), unhealthy weight status, and <i>APOE</i> genotypes in individuals of predominantly African descent aged 55 years and more. Genotyping of two single-nucleotide polymorphisms, rs7412 and rs429358, of the <i>APOE</i> gene was performed. <b>Results</b>: Among 310 individuals, the mean age was 75.64 years, the mean BMI was 25.94 kg/m², and the prevalence of CI was 18.1%. Most subjects were ε3/ε3 carriers (49%), while ε2-carriers and ε4-carriers represented 14.5% and 36.5%, respectively. Older age, the presence of undernutrition, and <i>APOE4</i> carriers were more frequently found in underweight vs. non-underweight individuals and in those with CI vs. those without CI. The adjusted odds ratios for prevalent CI were nearly four times higher for underweight individuals compared to obese individuals. Those carrying two ε4 alleles exhibited three times the odds of CI (OR = 3.31 (95% CI: 1.15-9.91), <i>p</i> = 0.026) compared to those with no ε4 alleles. <b>Conclusions:</b> In this cross-sectional study, being underweight and carrying the <i>ApoE</i> ε4 allele were independently associated with cognitive impairment. These findings suggest that monitoring weight changes and <i>APOE</i> genotypes in older adults may have clinical significance.