Maintenance of Cerebral Cortical Activity during Cognitive Challenge in Middle-aged Men and Women Genetically at Risk for Dementia: a Megnetoencephalographic Study

Title: EXERCISE BEHAVIOR AND MAINTENANCE OF CEREBRAL CORTICAL ACTIVITY DURING COGNITIVE CHALLENGE IN MIDDLE-AGED MEN AND WOMEN GENETICALLY AT RISK FOR DEMENTIA: A MEGNETOENCEPHALOGRAPHIC STUDY Sean Patrick Deeny, Doctor of Philosophy, 2005 Directed By: Professor Brad Hatfield, Department of Kinesiology Exercise is known to protect and enhance cognitive function in normal aging through increased blood flow and upregulation of neurotrophic factors in the brain. One recent study suggests that carriers of a known genetic risk factor for Alzheimer’s disease (AD), the apolipoprotein E (APOE) E4 allele, may exhibit a more profound benefit of exercise on neurocognitive function relative to non-E4 carriers. Brain imaging studies in cognitively normal, middle-aged E4 carriers have revealed deficits in temporal and parietal cortical function even in the absence of clinical symptoms of dementia. As exercise has been shown to protect these regions in normal aging, and even enhance cortical functioning, the current study employs magnetoencephalographic (MEG) measures of cortical activation during the Ericksen flanker task and the Sternberg working memory task to examine whether highly physically active 50-70 year old E4 carriers and non-carriers, who are free from dementia, exhibit greater cortical activation in task-related regions relative to their low-active counterparts. The results revealed that high-active participants, regardless of genotype, exhibited greater activation on the Ericksen flanker task in the right frontal and right temporal regions relative to low-active participants, while performing similarly on accuracy and reaction time (RT). On the Sternberg working memory task high-active E4 carriers exhibited greater activation than low-active E4 carriers in the right temporal region, while being undifferentiated from both the highactive and low-active non-E4 carriers. This effect was most pronounced in the 150200 ms post-stimulus time window. All groups performed similarly on accuracy and RT. The results suggest that high-resolution brain imaging methods are sensitive to differences in brain function in populations at different genetic risk for dementia prior to any signs of clinical impairment. Furthermore, the relationships between physical activity and brain function are measurable and distinguishable between groups of different genetic susceptibility on tasks and brain regions specific to AD-related neurocognitive decline. The findings support the notion that populations genetically at risk for dementia who remain sedentary may be at greater risk for decline in brain function relative to those who are physically active. EXERCISE BEHAVIOR AND MAINTENANCE OF CEREBRAL CORTICAL ACTIVITY DURING COGNITIVE CHALLENGE IN MIDDLE-AGED MEN AND WOMEN GENETICALLY AT RISK FOR DEMENTIA: A MEGNETOENCEPHALOGRAPHIC STUDY