Bradley D. Hatfield - US grants

[unreadable] DESCRIPTION (provided by applicant): The purpose of the present study is to address the relationship between physical activity history and brain processes in older men and women (50 - 65 years), particularly in those who are genetically at risk for late-onset Alzheimer's Disease (i.e., carriers of the APOE e4 allele. Neuroimaging studies reveal relative hypoactivation of brain metabolism in cognitively normal middle-aged e4 carriers during mental challenge in hippocampus and prefrontal cortex, indicative of metabolic abnormality in the same brain regions that are involved in AD. Recent epidemiological study indicates that physically active older e4 carriers show remarkable attenuation in cognitive decline relative to sedentary carriers of e4. In addition, recent animal research indicates neurotrophic effects of voluntary exercise on the hippocampal region. Collectively, these studies suggest an ameliorative influence of physical activity on the aging brain and a potential slowing of early-stage AD progression. Accordingly, 52 participants classified by physical activity level (high v low) and genotype (e4 allele present v absent) to form four groups will undergo magnetic source imaging (MEG) to assess hippocampal and prefrontal activity during cognitive challenge. We predict that physical activity status in middle-aged men and women will be associated with higher activity in hippocampus and lower activity in prefrontal region. Furthermore, the magnitude of these differences will be greatest between active and low-active carriers of the e4 allele. Detection of such related differences in brain activity in middle-aged adults would suggest an ameliorative influence of physical activity on age-related neurodegeneration and a protective role for AD progression. [unreadable] [unreadable] [unreadable] [unreadable]

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is an NIH/NIA-funded R21 study. Functional brain imaging data of patients at risk for Alzheimer's disease (by virtue of being carriers of the apoliproprotein e4 allele, APOE e4) has been shown to differ from controls when studied prior to onset of the disease. At the same time there is evidence suggesting that physical exercise reduces the risk of late onset Alzheimer's disease, especially in older APOE e4 carriers. Based on these findings the investigators plan to study subjects, using several MRI sequences for the purpose of developing a grant proposal. This grant proposal seeks to determine whether physical activity reduces the risk of late onset Alzheimer's in middle aged men and women who are carriers of APOE e4 and whether it attenuates abnormalities in neural processes that may be indicative of preclinical Alzheimer's Disease. All participants will be selected from a subgroup of participants that have participated in a University of Maryland College Park and that has already completed behavioral testing, genotyping and magnetoencephalography (MEG) studies of brain activity.