APOE‐ε4 status moderates the relationship between body mass index and hippocampal structure in older African Americans

Abstract

AbstractBackgroundGrowing evidence suggests that traditional body mass index (BMI) cutoff values may overestimate adiposity and its health consequences in African Americans. Further, while obesity disproportionately affects African Americans, obesity is inconsistently associated with Alzheimer’s disease (AD) in older adulthood. Examining the influence of BMI and its interaction with the strongest genetic risk factor of AD, the APOE‐ε4 allele, on hippocampal‐dependent cognitive performance and medial temporal lobe (MTL) structure may provide insights into the complex relationship between obesity and AD in older African Americans.MethodAnalyses included 70 cognitively normal older African Americans (mean age=69.50 years, SD=7.18; mean education=14.12 years, SD 2; 38.60% APOE‐4 allele carriers) who completed cognitive testing, saliva sampling for APOE genotyping, and structural neuroimaging to extract MTL cortical region/hippocampal subfield volumes and surface areas. Cognitive tests included the following measures of generalization and episodic memory: Concurrent Discrimination and Transfer Task, Acquired Equivalence Task, and Rey Auditory Verbal Learning Test. ANCOVAs were used to compare BMI groups (normal: 18‐24.9 kg/m2; overweight: 25‐29.9 kg/m2; class 1 obesity: 30‐34.9 kg/m22) and to test for BMIxAPOE interactions on cognitive and neuroimaging outcomes, while controlling for age, sex, education, literacy, and depressive symptomology.ResultThere was a statistically significant difference between BMI groups on Concurrent Discrimination and Transfer Task performance, p=.01, partial η 2=.18. The normal and class 2 obesity group committed significantly greater errors than either the overweight or class 1 obesity group, ps < .05. Significant BMIxAPOE interactions were identified for the following hippocampal subfield volumes and surface areas: left DG/CA3 and left CA1, ps < .05. For APOE‐ε4 non‐carriers, the normal BMI group had significantly smaller left DG/CA3 and CA1 subfields than the other groups. Among APOE‐ε4 carriers, the class 2 obesity group had smaller left DG/CA3 and CA1 subfields than the other groups.ConclusionBeing overweight may confer cognitive protection in older African Americans. However, obesity appears to be selectively detrimental to hippocampal subfield structure among APOE‐ε4 carriers while normal BMI may be deleterious to hippocampal subfield structure among APOE‐ε4 non‐carriers.