Early characterization of cognitive status and AD risk in African American men

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PROJECT SUMMARY/ABSTRACT Although past studies done primarily on white Americans report that men have a higher risk of mild cognitive impairment (MCI) and more rapid progression from MCI to AD, we do not know if this is also the case for African American men. Early characterization of cognitive status and Alzheimer’s disease (AD) risk in older African American men is a critical unmet challenge. There have been notably few dementia studies that included substantial numbers of older African American men. In particular, there is a paucity of neuroimaging data on older African American men in the years prior to, and during, cognitive decline to AD. We will utilize a cross- sectional study of older, urban African American men to characterize genetic, social, and environmental influences on the brain and neural markers indicative of cognitive status and AD risk. My training application will not only advance our understanding of neural changes and brain activity in older African American men, especially those exposed to conditions that put them at high risk for AD, but how their brain health relates to behavioral, genetic, neural, lifestyle, social, and environmental risk factors. Using observational study during the K99 phase, I will capture brain and neural pathways to cognitive changes/decline in African Americans, while undergoing extensive training to gain mastery of neuroimaging tools and concepts, proficiency in examining brain image biomarkers, neuropsychological assessments, and task-based fMRI testing and analyses. In the R00 phase, we will examine the neural pathways through which social and environmental factors impact cognition and identify individual variability that moderates their impact. Also, we will explore if social and environmental influences are mediated by their effect on the APOE ε4 and ABCA7-80 genes to impact cognitive status and AD risk in older African American men. Understanding the mechanisms involved in brain health and AD risk in older African American men will improve our knowledge of how AD affects men, and which tailored interventions are most effective for mitigating AD risk and improving cognitive function in African American men. The development of tailored interventions is increasingly urgent given the increase in the number of African American older adults experiencing AD and the AD-associated burdens to the individuals, families, and communities. At the end of the K99, I will have obtained intensive training experience in structural and functional neuroimaging analytic techniques and increased my knowledge of cognitive and genetic markers of AD. Further, I will have gained additional expertise in aging-related chronic illness risk reduction in pre-clinical African American men. The expertise would serve as a basis for my R00 and future independent research, where I would focus on social and environmental determinants of health to observe and document factors that impact brain health and prevent Alzheimer’s disease in urban African American men.