The National Heart, Lung, and Blood Institute (NHLBI) and National Institute of Neurological Disorders and Stroke (NINDS) convened a working group (WG) on Vascular Contributions to Cognitive Impairment and Dementia (VCID) in Bethesda, Maryland. The objectives of the working group were to identify research priorities that complement and expand on the VCID Research Milestones defined by the Alzheimer's Disease-Related Dementias (ADRD) Summit 2016, including those within NHLBI’s mission, that will guide the field for the next 5-10 years.
Dementia syndromes are neurodegenerative disorders characterized by cognitive impairment that are sufficiently severe to interfere with daily function. Alzheimer’s Disease (AD) is the most common dementia diagnosis. However, AD as a clinical syndrome has mixed pathology and multifactorial etiology. Emerging evidence suggests that most clinical AD cases, especially those in persons over the age of 80, have both classic AD plaques and tangles pathology and vascular pathology. VCID is defined as the aging neurovascular unit being confronted with and failing to cope with biological insults due to systematic and cerebral vascular disease, proteinopathy including Alzheimer’s biology, metabolic disease, and immune affront, resulting in cognitive decline. VCID research overlays multiple clinical diagnoses, including cerebro- and cardio-vascular disease, stroke, AD and other types of dementia, some of which involve neither AD or stroke.
The societal burden of dementia in the US is substantial and growing. Estimates suggest as many as 5.7 million Americans have AD, including one in nine adults age 65 years or older. AD is the sixth leading cause of death in the United States, and the annual costs of direct care for people with AD exceed $200 billion, which is comparable to that of cardiovascular diseases (CVD). Unfortunately, at this time dementia cannot be effectively treated, prevented or slowed down, and the burden of AD/ADRD is expected to grow, in large part as a result of the rising number of people living into older age with cardiometabolic comorbidities. Although recent evidence from Framingham Heart Study suggests a decline in incidence of dementia, a better understanding of overall trends in incidence and prevalence of dementia are needed given the aging of the U.S. population.
Besides the effects of aging, chronic systemic comorbidities are associated with cognitive outcomes and the common dementia-associated pathologies. These AD/ADRD research areas are of interest to both the NHLBI and the NINDS and include, but are not limited to: cardio- and cerebrovascular disease, metabolic disorders of lipid and glucose metabolism including diabetes, and immune dysfunction, as well as obesity and behavioral risks factors for these diseases, such as smoking, dietary behavior, physical inactivity, and stress. The racial/ethnic and socioeconomic health disparities in ADRD have been described yet are not well understood, and often mirror patterns in other age-related comorbidities and ADRD/VCID risk factors. We expect that promoting a fuller and better understanding of the biological mechanisms of VCID across the wide spectrum of pathologies, chronic systemic comorbidities, and other risk factors, may lead to potential prevention and treatment strategies to decrease the burden of dementia.
NHLBI, often in collaboration with NINDS, the National Institute on Aging (NIA), and other NIH institutes, supports several well-characterized, longitudinal, population-based cohort studies and clinical trials in diverse populations to understand key determinants of vascular and cerebrovascular outcomes; clinical and subclinical markers of pathology across the body (including brain vessels); and natural history and pathological mechanisms of, and prevention and treatment of various diseases, including hypertension, atherosclerosis, sleep disorders, and their brain manifestations. These cohorts are a rich source of data and stored biospecimens, that are being leveraged using multi-omic screening methods for targeted and agnostic research. These approaches will promote development of new imaging and blood-based diagnostics/biomarkers for people with symptomatic disease – both AD and ADRD – as well as asymptomatic individuals. These approaches will also help us understand the relative contribution of the potential vascular contributions to AD and ADRD. This working group was convened to evaluate status of VCID basic and epidemiological research, to identify research gaps and barriers, and to recommend future research opportunities.
The WG presentations and discussions focused on the following areas:
The WG identified several important challenges and barriers to better understanding of the contributions of vascular factors to dementia:
The WG identified the following research opportunities:
The working group plans to prepare a manuscript for publication in a peer-reviewed journal.
Division of Cardiovascular Sciences
National Heart, Lung, and Blood Institute
National Institutes of Health