Alzheimer’s disease and related dementias (ADRD) are an expanding worldwide crisis. In the absence of scientific breakthroughs, the global prevalence of ADRD will continue to increase as more people are living longer. Racial or ethnic minority groups have an increased risk and incidence of ADRD and have often been neglected by the scientific research community. There is mounting evidence that vascular insults in the brain can initiate a series of biological events leading to neurodegeneration, cognitive impairment, and ADRD. We are a group of researchers interested in developing and expanding ADRD research, with an emphasis on vascular contributions to dementia, to serve our local diverse community. Toward this goal, the primary objective of this review was to investigate and better understand health disparities in Alabama and the contributions of the social determinants of health to those disparities, particularly in the context of vascular dysfunction in ADRD. Here, we explain the neurovascular dysfunction associated with Alzheimer’s disease (AD) as well as the intrinsic and extrinsic risk factors contributing to dysfunction of the neurovascular unit (NVU). Next, we ascertain ethnoregional health disparities of individuals living in Alabama, as well as relevant vascular risk factors linked to AD. We also discuss current pharmaceutical and non-pharmaceutical treatment options for neurovascular dysfunction, mild cognitive impairment (MCI) and AD, including relevant studies and ongoing clinical trials. Overall, individuals in Alabama are adversely affected by social and structural determinants of health leading to health disparities, driven by rurality, ethnic minority status, and lower socioeconomic status (SES). In general, these communities have limited access to healthcare and healthy food and other amenities resulting in decreased opportunities for early diagnosis of and pharmaceutical treatments for ADRD. Although this review is focused on the current state of health disparities of ADRD patients in Alabama, future studies must include diversity of race, ethnicity, and region to best be able to treat all individuals affected by ADRD.

BackgroundIt is estimated that nearly 100,000 Alabamians have Alzheimer’s disease (AD). There is strong evidence that neurovascular uncoupling, cerebral blood flow reductions and dysregulation, and breakdown of the blood‐brain barrier (BBB), including the loss of pericytes, are early events in the AD pathophysiological cascade. Health, lifestyle, and socioeconomic risk factors across racial groups, and/or genetic risk factors, may account for this increased AD risk. Aged Black Americans have twice the risk of experiencing AD or other dementias compared to aged Whites. 26.8% of the Alabama population is Black American. Furthermore, over a million people in Alabama live in rural areas (USDA‐ERS), leading to healthcare professional shortages, and in designated medically underserved areas. Relatively little is known about the role of cerebrovascular mechanisms in the pathogenesis of dementia and AD and potential therapeutic targets within the neurovascular system, especially as they relate to health disparities. Thus, determining whether health disparities via vascular or genetic risk factors leads to neurovascular dysfunction and ultimately AD is essential.MethodBlood was collected from middle‐aged diverse individuals (67% Black, n = 12 and 33% White, n = 6, 61% of participants were female) that reside in the South Alabama vicinity. Plasma and buffy coat were used for biomarker assays and APOE genotyping, respectively. We identified APOE genotype using DNA extraction and PCR‐RFLP. We used MesoScale Discovery’s MESO QuickPlex SQ to quantify vascular biomarkers, tau and neurofilament light chain. Measurements of amyloid‐beta, inflammatory cytokines and other biomarkers are underway.Result67% of Blacks and 17% of Whites were APOE‐ε4 carriers. 39% of participants reside in designated rural or medically underserved areas. Blacks had increased bFGF, Flt‐1, VEGF‐C and tau. APOE‐ε4 carriers had increased VEGF‐C and tau. Females had increased Flt‐1 and VEGF‐A. Individuals residing in rural/medically underserved areas had increased bFGF.ConclusionWe observed a large % of APOE‐ε4 carriers in Black participants. The increase in VEGF‐C and tau in Black participants may have been provoked by APOE‐ε4 genotype. Vascular health and peripheral tau may play a crucial role in the development of AD. Improving modifiable vascular risk factors early with interventions such as exercise may help prevent AD.