The National Heart, Lung, and Blood Institute (NHLBI); the National Institute of Neurological Disorders and Stroke (NINDS); and National Institute on Aging (NIA) convened a multidisciplinary working group on Future Clinical Trials to Test Promising Approaches for Reducing Vascular Contributions to Cognitive Impairment and Dementia (VCID). The objectives of the working group are to examine lessons learned from recently completed VCID trials and the promise of ongoing trials, and to identify gaps and opportunities for additional trials that may deliver more potent interventions, including both pharmacological and lifestyle interventions that target vascular and other risk factors.
Dementia is a constellation of neurodegenerative disorders characterized by cognitive impairment that is sufficiently severe to interfere with daily function. The societal burden of dementia is expected to increase in the U.S. and globally in the foreseeable future. Alzheimer’s Disease (AD) is the most common dementia diagnosis, with an estimated 5.8 million Americans currently living with the disease. Growing evidence suggests that dementia has mixed pathology. Clinical AD often has vascular pathology, and epidemiological studies suggest that up to one-third of cases of dementia may be attributed to modifiable vascular risk factors such as smoking, blood pressure, blood sugar, cholesterol, diet, and exercise. Thus, vascular contributions to cognitive impairment and dementia (VCID) are an important target for prevention trials. The Systolic Blood Pressure Intervention Trial (SPRINT) Memory and Cognition in Decreased Hypertension (SPRINT MIND) results showed that intensive lowering of blood pressure reduced risks for mild cognitive impairment (MCI), but did not significantly reduce dementia risk. It is possible that treatment of any single vascular risk factor may be insufficient to cause a large reduction in the risk of clinically significant cognitive impairment or dementia. The Finnish FINGER trial suggested that interventions on multiple vascular risk factors may need to be targeted, including physical activity, nutritional counseling, and cognitive and social stimulation. The FINGER trial provided the impetus for the U.S. POINTER trial, which is currently underway.
Working Group Purpose and Objectives
This workshop is timely given that the NIH Alzheimer’s Disease-Related Dementias Summit in 2019 highlighted the need for clinical trials addressing VCID. The main goal of the workshop was to determine if there are compelling research opportunities for clinical trials to test single or combined interventions for the primary and secondary prevention of vascular contributions to VCID and that align with the following Summit recommendations under the Human-Based Studies focus area.
Concise Summary of Discussions
Rich interdisciplinary discussions were held to inform the design of future clinical trials and also to sharpen the needs for additional epidemiological and basic science studies. Presentations and discussions were centered around the following areas.
The working group identified several important questions that might be answered by new trials as well as challenges and research opportunities.
The meeting participants will develop a workshop report for publication in a peer-reviewed journal. The report will highlight discussions that occurred at the workshop and the research opportunities identified by the working group.
Lawrence J. Fine, MD, DrPH
Division of Cardiovascular Sciences, NHLBI
Working Group Participants
Presenters and Discussants