VCID: Develop and validate VCID biomarkers

AD-Related Dementias Focus

Develop and validate markers of VCID in diverse populations using 1) cognitive, physical, or other functional assessments, and 2) biomarkers of key vascular processes, including in the most common scenario where VCID is accompanied by AD in human studies.

2025 RFA-AG-15-010: Interdisciplinary Research to Understand the Vascular Contributions to Alzheimer's Disease (R01) RFA-NS-16-019: Small Vessel Vascular Contributions to Cognitive Impairment and Dementia (VCID) Biomarkers Consortium: Coordinating Center (U24) RFA-NS-16-020: Small Vessel Vascular Contributions to Cognitive Impairment and Dementia (VCID) Biomarkers Development Projects (UH2/UH3) RFA-NS-19-014: Center without Walls for PET Ligand Development for Alzheimer's disease related dementias (ADRDs) (U19) RFA-NS-20-013: White Matter Disease Etiology of Dementia in the U.S. Including in Health Disparities Populations RFA-NS-21-004: Small Vessel VCID Biomarkers Validation Consortium Coordinating Center (U24 Clinical Trial Not Allowed) RFA-NS-21-005: Small Vessel VCID Biomarkers Validation Consortium Coordinating Center (U24 Clinical Trial Not Allowed) NOT-NS-21-038: Hyperacute MRI Imaging Studies to Understand How Brain Changes Affect AD/ADRD-Relevant Trajectories and Outcomes Post-Stroke RFA-NS-24-001: Using Multimodal Biomarkers to Differentially Diagnose ADRDs for Clinical Trials (U19 Clinical Trial Optional) NOT-NS-24-135: Notice of Special Interest (NOSI): Administrative Supplement Program to Add Fluid-based Biomarkers and APOE Genotyping to NINDS ADRD Human Subjects Research Grants 9.R In Progress Develop and validate longitudinally tracked noninvasive markers of key vascular processes related to cognitive and neurologic impairment. 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 1 2022 ADRD Summit: Vascular Contributions to Cognitive Impairment and Dementia (VCID) Milestone 4, Priority 1 News: NIH consortium takes aim at vascular disease-linked cognitive impairment and dementia Workshop: Imaging the Future of In vivo Neuropathological Diagnosis through Postmortem Analyses MarkVCID Diverse VCID: White Matter Lesion Etiology of Dementia in Diverse Populations Projects funded under RFA-NS-21-005 Select projects funded in FY22

  • Complete at least one human-based project to validate for clinical trials imaging and fluid-based biomarkers of small vessel VCID in that include general and diverse populations in the United States (at a minimum Black/African American, Hispanic/Latino, and White populations).
  • At least one clinically validated VCID biomarker that is clinical trial ready with a defined biomarker category and context of use.

Summary of Key Accomplishments

Until recently, diagnosis of brain arteriolosclerosis, which is one of the main pathologies of cerebral small vessel disease that contributes to cognitive decline and dementia, was only possible at autopsy. Through the NIH funded MarkVCID consortium, researchers have developed an assessment that combines MRI pictures of the brain with other factors, like age and gender, to measure arteriolosclerosis. Known as ARTS, this arteriolosclerosis biomarker is associated with an increased chance of cognitive decline two years later and shows good performance in predicting disease.

The MarkVCID consortium has also instrumentally validated several VCID biomarkers, such as plasma levels of the neurofilament light protein. Current work is focused on clinically validating these biomarkers, including in Black and Hispanic populations, for use in future clinical trials and for generating scientific breakthroughs in understanding and treating small vessel VCID.

A critical initial step in clinical management is to be able to detect cognitive impairment and dementia when a patient, relative, or care provider indicates concern. For this reason, the DetectCID consortium aims to establish, test, and validate assessment tools for detecting cognitive impairment, including dementia, in primary care and other forms of everyday clinical practice. A recent pragmatic clinical trial using one of the DetectCID paradigms that combines a five-minute cognitive assessment with a decision tree embedded in electronic health records demonstrated improved diagnosis and management in a diverse population of patients in New York City. This study provides evidence to promote practice change to improve dementia outcomes in primary care.

The key accomplishments summary is current as of July 2024.