Elucidate the multi-factorial mechanism of health disparities in aging population
Understanding health disparities in the prevalence and severity of dementia is critical to diversifying research cohorts and identifying effective therapy and interventions in the treatment. However, most studies strike to regress out disparity-specific differences instead of investigating how the neuropathological burden indeed differs by sex. More critically, there are several misconceptions about sex-linked biology and gender roles in the disease progression. The clinical goal of this proposal is to address three important scientific questions as follows: (1) Are women at greater risk than men? (2) How to stratify the biological mechanisms and environmental exposures from the synergistic effect of health disparities? (3) How to integrate the understanding of health disparities into precision medicine approaches? To address these questions, the methodological goal of this project is to apply and develop a set of computational approaches to advance the understanding of sex/gender disparities in AD, while harmonizing and analyzing a large-scale AD-related database obtained from seven different studies. Specifically, we will create a lifespan whole-brain mapping of disparity-specific effect on dementia where the neurodegeneration events (including neuropathology, metabolism, and structure/function alterations) on the underlying brain region and connectome wirings differ in different groups, which allows us to capture the dynamics of health disparity factors in disease progression. We will further elucidate the synergistic effect of health disparities triggered by biological sex or environmental consequences of gender. Specifically, we put our spotlight on the gene-by-environment interaction by examining the joint effect of genetic determinants and environmental exposures on Health disparities. Lastly, we will translate our findings on health disparities to the clinic arena by characterizing the selective survival advantages in the incidence of AD by which sex/gender differences could differentially affect men and women. We will examine the selective survival advantages underlying the above multiple scenarios, which have the great potential to identify individuals at higher risk of dementia and differences in disease progression. Successfully executing this project will provide a new window to understand health disparities and suggest novel approaches for the disease-modifying therapy in clinical practice.