ADRD Specific Milestone
Foster basic science research on neurovascular unit function and how it is impacted by the following: aging, cardiovascular disease, AD pathology and genetics.
- Support at least two new basic science research projects designed to understand the role of the perivascular (CSF) and paravascular (lymphatic) clearance pathways in normal brain health and whether these systems help protect the brain from VCID and other AD/ADRD dementias, as well as their progression.
- Support new research to determine: (i) how the neurovascular unit contributes to neurovascular coupling, i.e. regulation of brain blood flow across different vascular zones (arterioles, capillaries and venules), (ii) how normal neurovascular unit function is impacted by VCID risk factors (e.g. cardiovascular and cerebrovascular disease, metabolic factors, lifestyle factors, hypertension, TBI, AD/ADRD pathology and genetics, and aging), and by other AD/ADRD disorders, (iii) the relationship between blood brain barrier function and neurovascular unit function in health and in AD/ADRD.
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.
This information is current as of March 2022.
- Research Implementation Area
- AD Related Dementias - Specific
- In Progress
- 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)