FUNCTIONAL CONNECTIVITY PATTERNS ASSOCIATED WITH AGING, PHYSICAL ACTIVITY, AND GENETIC RISK FOR ALZHEIMER’S DISEASE IN HEALTHY HUMAN BRAIN NETWORKS.

Abstract

Leisure time physical activity (PA) and exercise training help to improve and maintain cognitive function in healthy older adults and in adults with the APOE-ε4 allele, a genetic risk for Alzheimer’s Disease (AD). Earlier work finding increased functional connectivity in the Default Mode Network (DMN) after a 12-week walking intervention in 16 older adults with mild cognitive impairment is presented in Chapter 3. The primary dissertation study investigating differences in brain function depending on PA level and genetic risk for AD prior to changes in cognition is presented in Chapters 4-6. Useable resting state and anatomical MRI scans were collected from 69 healthy adults (22-51 years) as well as saliva for APOE genotyping (carriers defined as homozygotes or heterozygotes of the ɛ4 allele) and responses to the Paffenbarger Physical Activity Questionnaire (High PA >1500 kcal, Low PA <1500 kcal per week). The following network measures of functional connectivity were calculated: global efficiency; node strength of Default Mode Network (DMN) and Fronto-Parietal Network (FPN) hubs and hippocampal subsections; and long-range connectivity of the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) in the DMN. Multiple linear regression analysis revealed statistically significant results for the long-range connectivity of the left PCC, a prominent hub of the DMN, and left mPFC. The differences in projected trajectories of the connectivity are potentially reflective of the compensatory time-course in our participants based on interactions of PA level and APOE status. The Low PA non-carriers had a positive slope indicating increased connectivity with age while carriers and non-carriers in the High PA category had horizontal aging trajectories. PA is associated with cognitive reserve (CR), a term describing the protection and adaptation of cognitive processes through neural efficiency and compensation mechanisms, and it is possible the Low PA non-carriers exhibited compensatory increases in connectivity of the left mPFC-PCC earlier than High PA study participants due to lower levels of CR. The promising findings that rs-fMRI can be used as an early detection of brain changes sensitive to PA levels and APOE-ɛ4 status are critical to the research and treatment of AD.