Apoe Genotype, Aerobic Fitness, And Cerebral Cortical Activation During Working Memory Challenge In Middle-aged Adults

Abstract

PURPOSE: APOE e4 genotype is linked to accelerated age-related cognitive decline and is an established risk for Alzheimer's disease. Cardiovascular fitness may counteract this liability based on animal studies that reveal remarkable neurobiological benefits in the brain. The present study determined if cardiovascular fitness is positively associated with neurocognitive integrity in e4 carriers during memory challenge. METHODS: After providing informed consent and health history, 22 men and women aged 50-70 years completed cognitive screening by interview and the Rockport Walk test to determine aerobic fitness. Genotyping preceded a battery of cognitive tests (APOE e4 carriers, n=11.) Working memory challenge included presentation of a modified Sternberg Letter task (stimuli of 5- or 7-letters) during non-invasive magnetoencephalographic (MEG) brain imaging. Averaged M170 amplitude and latency, derived from global MEG activity recorded from 157 sites, were separately and hierarchically regressed on age, education, genotype, aerobic fitness (estimated VO2max [ml/kg/min]), and the interaction between genotype and aerobic fitness. We predicted that aerobic fitness would be positively related to M170 amplitude and negatively related to M170 latency, and that the interaction of APOE genotype would explain additional unique variance, particularly as the task became more difficult (i.e., 7-letter condition). RESULTS: The Rockport Walk test produced an estimated VO2max of 32.2 ml/kg/min (± 8.6). M170 amplitude in response to 5- letter memory probe revealed a slope of.95 and R2 value of.56, p=.001 for aerobic fitness. M170 amplitude in response to the 7-letter memory probe revealed a slope of.72 and R2 value of.42, p=.02 for aerobic fitness. Latency was not related to any of the independent variables. CONCLUSIONS: Aerobic fitness is positively associated with cortical activation during memory challenge across varying levels of load, regardless of APOE genotype.