APOE Genotype Modifies the Association of Fusiform Gyrus Cerebral Metabolic Rate of Oxygen Consumption and Object Naming Performance

Abstract

Background: The apolipoprotein E (APOE) ɛ4 allele confers risk for age and Alzheimer’s disease related cognitive decline but the mechanistic link remains poorly understood. Blood oxygenation level dependent (BOLD) response in the fusiform gyrus (FG) during object naming appears greater among APOE ɛ4 carriers even in the face of equivalent cognitive performance, suggesting neural compensation. However, BOLD is susceptible to known age and APOE-related vascular changes that could confound its interpretation. Objective: To address this limitation, we used calibrated fMRI during an object naming task and a hypercapnic challenge to obtain a more direct measure of neural function – percent change cerebral metabolic rate of oxygen consumption (%ΔCMRO2). Methods: Participants were 45 older adults without dementia (28 ɛ4–, 17 ɛ4+) between the ages of 65 and 85. We examined APOE-related differences in %ΔCMRO2 in the FG during object naming and the extent to which APOE modified associations between FG %ΔCMRO2 and object naming accuracy. Exploratory analyses also tested the hypothesis that %ΔCMRO2 is less susceptible to vascular compromise than are measures of %ΔCBF and %ΔBOLD. Results: We observed a modifying role of APOE on associations between FG %ΔCMRO2 and cognition, with ɛ4 carriers (but not non-carriers) demonstrating a positive association between right FG %ΔCMRO2 and object naming accuracy. Conclusion: Results suggest that the relationship between neural function and cognition is altered among older adult APOE ɛ4 carriers prior to the onset of dementia, implicating CMRO2 response as a potential mechanism to support cognition in APOE-related AD risk.