The Differential Benefits Of Aerobic Fitness For Cognitive Performance As A Function Of ApoE Genotype

Abstract

The apolipoprotein E epsilon 4 (ApoE-ε4) allele is a common susceptibility gene for late-onset cognitive decline and Alzheimer's dementia (AD). However, since this gene is neither necessary nor sufficient for the development of these problems, it would be beneficial to identify risk modifiers, some of which may interact with ApoE-ε4 allele in the prediction of cognitive outcomes. Purpose: Therefore, the purpose of this study was to examine the effects of ApoE-ε4 gene dose, aerobic fitness (VO2max), and their interaction on cognitive measures hypothesized to be sensitive to the interaction. Methods: Data were collected from 85 cognitively normal older women (51–77 yrs, M = 61.8 yrs). Participants provided blood samples for ApoE genotypes, understood that they would receive no information about their ApoE genotypes, completed a battery of clinical ratings and neuropsychological tests, and performed a VO2max test. The sample included 7 ε4 homozygotes, 25 ε4 heterozygotes, and 53 ε4 non-carriers. Hierarchical regression analyses were conducted with depression, years of education, time between cognitive and fitness tests, and age entered first, followed by main effects for VO2max and ApoE-ε4 gene dose, followed by the interaction terms for VO2max by ApoE-ε4. Results: After controlling for main effects, the interaction of ApoE-ε4 gene dose by aerobic fitness predicted a significant (p < .05) percentage of the variance in performance (R2 = 7–9%) on several subscales of the Wechsler Adult Intelligence Scale (Perceptual Organization, Information, Block Design, Digit Symbol Substitution) and on the Complex Figures Test recall scale. Examination of the results indicated that the findings were consistent across all cognitive measures and were such that VO2max was positively related to cognitive performance for the ε4 homozygotes and was generally not related to performance for the ε4 heterozygotes or the ε4 non-carriers. Conclusion: These findings suggest that aerobic fitness is associated with better cognitive performance in homozygous carriers of a common AD susceptibility gene. Larger samples, our ongoing longitudinal assessments, the conductance of true-experimental studies, and the study of persons with other AD risk factors are needed to further demonstrate the protective effects of aerobic fitness on the subsequent development of cognitive decline and probable AD in persons at higher risk for these problems. Supported by NIA grants 1-R03AG022621 and P30 AG19610, NIMH grant RO1 MH057899, the Alzheimer's Association grants IIRG-98-068 and IIRG-98-078, the Arizona Alzheimer's Research Center, and the Arizona State University Stress Center.