Neurovascular Dysfunction in Diverse Communities With Health Disparities—Contributions to Dementia and Alzheimer’s Disease

Abstract

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.

Global rural health disparities in Alzheimer's disease and related dementias: State of the science

“…A small percentage of all Alzheimer's disease (AD) cases, the most common type of dementia, are autosomal-dominant AD (ADAD) caused by known mutations in Presenilin-1 (PSEN1), Presenilin-2 (PSEN2), and Amyloid protein precursor (APP) genes. 29 Most AD cases are sporadic, without a primary genetic cause. However, numerous genome-wide association studies have identified genetic risk factors associated with sporadic AD.…”

“…Most AD cases are sporadic, without a primary genetic cause. However, numerous genome‐wide association studies have identified genetic risk factors associated with sporadic AD 29 . These studies largely encompassed Europeans or Americans of European descent, and repeatedly identify apolipoprotein E (APOE) ε4 as the greatest genetic risk factor for sporadic AD 30 .…”

“…A recent study with > 112 million adults described that more than 55% of this global rise in mean body mass index (BMI) was due to BMI increases in rural areas 38 . Obesity is closely associated with metabolic syndrome, hyperlipidemia, insulin resistance, and diabetes 29 . Obesity, together with several of these chronic illnesses is associated with increased ADRD risk 10 .…”

“…However, numerous genome-wide association studies have identified genetic risk factors associated with sporadic AD. 29 These studies largely encompassed Europeans or Americans of European descent, and repeatedly identify apolipoprotein E (APOE) ε4 as the greatest genetic risk factor for sporadic AD. 30 In another review that included data from community dwellers without dementia in 38 countries globally, Africans and Caucasians were shown to be the most common carriers of APOE ε4, F I G U R E 1 Barriers and facilitators to rural ADRD disparities.…”

“…38 Obesity is closely associated with metabolic syndrome, hyperlipidemia, insulin resistance, and diabetes. 29 Obesity, together with several of these chronic illnesses is associated with increased ADRD risk. 10 In a similar vein, hypertension is the leading modifiable risk factor for ADRD.…”