VCID Basic Research: Role of the neurovascular unit (Milestone 2.Q)
AD-Related Dementias Focus
Study the neurovascular unit structure and function to establish how it is impacted by VCID.
Success Criteria
- At least two new projects to understand the role of perivascular and paravascular clearance pathways that may protect the brain from VCID.
- At least three new projects to determine how normal neurovascular unit function and blood brain barrier function are impacted by VCID risk factors.
Summary of Key Accomplishments
Several recent NIH studies have resulted in significant new understanding of the inter-relationship between brain cells and their blood vessels, known collectively as the "neurovascular unit", and how they are impacted in AD/ADRD. For example, in 2019, one of these studies reported that brain waste clearance pathways, also known as perivascular “glymphatic pathways”, not only contribute to the removal of beta-amyloid from the brain but are compromised by long term hypertension in rats – a clear example of interaction between hypertension and brain waste clearance mechanisms that may result in increased risk for different types of dementia. This emerging body of work has resulted in a new hypothesis of how hypertension can lead to dementia-related brain changes, opening up new avenues of investigation and potential drug targets for future research.
The key accomplishments summary is current as of July 2022.
- Research Implementation Area
- Research on Disease Mechanisms
- Timeline
- 2016–2026
- Status
- In Progress
Accomplishments/Implementation Activities
Funding Initiatives
- RFA-NS-16-021: Mechanistic Basis of Diffuse White Matter Disease in Vascular Contributions to Cognitive Impairment and Dementia (VCID)(R01)
- PAR-18-413: Mechanistic Basis of Diffuse White Matter Disease and Small Vessel Pathology in Vascular Contributions to Cognitive Impairment and Dementia (VCID)(R01)
- RFA-AG-17-055: Brain Lymphatic System in Aging and Alzheimer's Disease (R01)
- RFA-NS-19-039: Mechanistic Basis of Diffuse White Matter Disease in VCID (re-issue)
- PAR-19-070: Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01)
- RFA-NS-20-004: Molecular Mechanisms of Blood-Brain Barrier Function and Dysfunction in Alzheimer's disease and Alzheimer's related dementias
- RFA-NS-20-013: White Matter Disease Etiology of Dementia in the U.S. Including in Health Disparities Populations
- RFA-AG-20-025: Understanding Senescence in Brain Aging and Alzheimer’s Disease (R01)
Research Programs and Resources
- Mechanistic Basis of Diffuse White Matter Disease and Small Vessel Pathology in Vascular Contributions to Cognitive Impairment and Dementia (VCID) R01)
- Mechanistic Basis of Diffuse White Matter Disease in VCID (re-issue)
- Diverse VCID: White Matter Lesion Etiology of Dementia in Diverse Populations
- Determinants of Incident Stroke Cognitive Outcomes and Vascular Effects on Recovery (DISCOVERY)
Relevant Recommendations
- 2016 ADRD Summit: Vascular Contributions to Cognitive Impairment and Dementia (VCID), Including Vascular Cognitive Impairment and Vascular Dementia (VCID) Focus Area 1: Basic Mechanisms and Experimental Models, Recommendation 2
- 2022 ADRD Summit: Vascular Contributions to Cognitive Impairment and Dementia (VCID) Milestone 2, Priority 3