Faculty, Staff and Student Publications

Language

English

Publication Date

2-1-2026

Journal

Annals of Neurology

DOI

10.1002/ana.78040

PMID

40977537

PMCID

PMC13126552

PubMedCentral® Posted Date

4-20-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Objective: To establish a framework for validating candidate biomarkers of cerebral small vessel diseases (SVD) associated with cognitive impairment and characterize individuals enrolled by the MarkVCID2 consortium under this framework.

Methods: Participants age 60 to 90 years were enrolled across 17 MarkVCID2 sites. Recruitment was targeted to enrich in cognitive symptoms (mild dementia, mild cognitive impairment, subjective cognitive decline), defined risk factors (diabetes mellitus, advanced hypertension), and Black/African American, White, and Hispanic/Latino subgroups. Enrolled participants underwent baseline visits that included cognitive testing, multimodal magnetic resonance imaging (MRI), and biofluid collection. Provisional risk for SVD-related cognitive decline was estimated primarily by baseline cognitive symptoms plus SVD risk factors. Adjudicated risk status was estimated by cognitive symptoms plus presence of moderate-to-severe white matter hyperintensities, microbleeds, or lacunes on baseline MRI.

Results: MarkVCID2 enrolled 1883 individuals age 73.4 ± 7.5 years, 65.0% female, 24.2% Hispanic, and 27.1% non-Hispanic Black. Among enrollees, 44.8% were provisionally designated high-risk. After baseline MRI, 48.5% were categorized as adjudicated high-risk status, with substantial recategorization both from low- to high-risk (primarily because of MRI lesions without SVD risk factors) and high- to low-risk (primarily suspected cognitive impairment at screening not confirmed by baseline testing).

Interpretation: MarkVCID2 baseline data indicate successful enrollment of diverse individuals enriched in factors associated with SVD-related cognitive decline. Changes over 3 years of longitudinal follow-up will be analyzed to validate the candidate biomarkers for 2 projected contexts of use: subject selection (identifying likelihood of future SVD progression) and study outcome (efficiently measuring SVD progression). ANN NEUROL 2026;99:449-458.

Keywords

Humans, Cerebral Small Vessel Diseases, Female, Aged, Male, Middle Aged, Biomarkers, Aged, 80 and over, Cognitive Dysfunction, Magnetic Resonance Imaging, Risk Factors

Published Open-Access

yes

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