VCID Clinical Research: Determine interrelationship between VCID and AD biomarkers in humans

AD-Related Dementias Focus

Understand the impact on VCID of other known dementia risk factors (e.g., aging, genetics) and co-morbid neurodegeneration along the life-course in diverse populations to establish VCID interactions with other dementia disease processes.

2029 RFA-AG-15-010: Interdisciplinary Research to Understand the Vascular Contributions to Alzheimer's Disease (R01) PAR-17-054: Leveraging Existing Cohort Studies to Clarify Risk and Protective Factors for Alzheimer’s Disease and Related Dementias (R01) RFA-NS-19-012: Post-Stroke Vascular Contributions to Cognitive Impairment and Dementia (VCID) in the United States Including in Health Disparities Populations (U19 Clinical Trial Not Allowed) PAR-19-167: Development and Validation of Advanced Mammalian Models for Alzheimer's Disease-Related Dementias (ADRD) (R61/R33) RFA-NS-20-013: White Matter Disease Etiology of Dementia in the U.S. Including in Health Disparities Populations NOT-NS-21-038: Hyperacute MRI Imaging Studies to Understand How Brain Changes Affect AD/ADRD-Relevant Trajectories and Outcomes Post-Stroke RFA-NS-21-004: Small Vessel VCID Biomarkers Validation Consortium Coordinating Center (U24 Clinical Trial Not Allowed) RFA-NS-21-005: Small Vessel VCID Biomarker Validation Consortium Sites (U01 Clinical Trials Not Allowed) NOT-NS-22-001: Postmortem Pathology, Cellular, and Molecular Analyses to Determine the Significance of White Matter Lesions and other Imaging Findings of Presumed Vascular Origin During Life PAR-23-211: Mechanistic Investigations into ADRD Multiple Etiology Dementias (R01 - Clinical Trial Not Allowed) PAR-24-147: Mechanistic Investigations into ADRD Multiple Etiology Dementias (R01 - Clinical Trial Not Allowed) PAR-24-196: Mechanistic and Hemodynamic Basis of Diffuse White Matter Disease in Vascular Contributions to Cognitive Impairment and Dementia (VCID)(R01 - Clinical Trial Not Allowed) 2.S Achieved Determine interrelationships among aging, cerebrovascular disease and risk factors, resilience factors, genetic variants, amyloid, tau, and neurodegeneration. DN 2016 ADRD Summit: Vascular Contributions to Cognitive Impairment and Dementia (VCID), Including Vascular Cognitive Impairment and Vascular Dementia (VCID) Focus Area 2: Human-Based Studies, Recommendation 2 2022 ADRD Summit: Vascular Contributions to Cognitive Impairment and Dementia (VCID) Milestone 6, Priority 4 News: SPRINT-MIND: Intensive blood pressure control may slow age-related brain damage (SPRINT-MIND) Workshop: Imaging the Future of In vivo Neuropathological Diagnosis through Postmortem Analyses Research on Disease Mechanisms VCID and Stroke in a Bi-racial National Cohort (REGARDS) MarkVCID Post-Stroke Vascular Contributions to Cognitive Impairment and Dementia (VCID) in the United States Including in Health Disparities Populations (U19 Clinical Trial Not Allowed) Development and Validation of Advanced Mammalian Models for Alzheimer's Disease-Related Dementias (ADRD) (R61/R33) Diverse VCID: White Matter Lesion Etiology of Dementia in Diverse Populations Select projects funded in FY21 Select projects funded in FY22 Mind Your Risks

  • One or more studies to understand independent associations between biomarkers of VCID and biomarkers of other dementia-associated brain pathologies and comorbidities in a human cohort sufficiently powered to answer key questions in at least two populations that experience health disparities.

Summary of Key Accomplishments

Researchers are finding that most people diagnosed with dementia have disease markers of more than one form of dementia (e.g., multiple AD and ADRD-related disease markers), or “mixed pathologies.”

NIH-funded scientists recently discovered and coined a term for a new dementia-related pathology, which they call “LATE,” or limbic-predominant age-related TDP-43 encephalopathy. LATE is frequently found in individuals diagnosed with different forms of dementia, including Alzheimer’s-type dementia, VCID, and mixed pathology dementia. NIH issued two open funding opportunities (one in FY23 and one in FY24) to better understand (1) the mechanisms and causal relationships between TDP-43 pathology and clinical phenotypic outcomes and (2) mechanisms underlying how and when interactions among different drivers of dementia (such as VCID) lead to worsening pathophysiology and outcomes.

In addition, NIH-funded researchers recently found evidence that cerebrovascular disease (which can contribute to VCID), tau, and TDP-43 proteinopathy together may cause white matter microstructural damage, which may affect cognition. This new understanding that multiple disease processes often underly dementia suggests the need to intervene in multiple dementia-related pathways in the same individual and provides new prevention and treatment targets for future research.

The key accomplishments summary is current as of June 2024.