Evidence map›Paper›PMID 40977537›Full record

ArticleAnnals of neurology2026

MarkVCID2 Consortium for Clinical Validation of Biomarkers of Cerebral Small Vessel Disease: Validation Framework and Baseline Characteristics.

Steven M Greenberg, Marylin S Albert, Hongyu An, Konstantinos Arfanakis, Arnold M Evia, Arvind Caprihan, Andria L Ford, Myriam Fornage, Gregory S Day, Jason D Hinman and 35 more

Abstract readValidation StudyMulticenter Study
In one paragraph

Article in Annals of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

45 authors.

Steven M GreenbergDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0003-1792-8887
Marylin S AlbertDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Hongyu AnMallinckrodt Institute of Radiology, Washington University in St Louis School of Medicine, St. Louis, MO, USA.ORCID 0000-0001-6459-2269
Konstantinos ArfanakisDepartment of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA.ORCID 0000-0001-9705-597X
Arnold M EviaRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.ORCID 0000-0003-2262-890X
Arvind CaprihanThe Mind Research Network, Albuquerque, NM, USA.ORCID 0000-0002-4810-359X
Andria L FordMallinckrodt Institute of Radiology, Washington University in St Louis School of Medicine, St. Louis, MO, USA.ORCID 0000-0003-0605-8943
Myriam FornageBrown Foundation Institute of Molecular Medicine, McGovern Medical School and Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID 0000-0003-0677-8158
Gregory S DayDepartment of Neurology, Mayo Clinic in Florida, Jacksonville, FL, USA.ORCID 0000-0001-5133-5538
Jason D HinmanDavid Geffen School of Medicine, Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0002-0872-5044
Gregory A JichaSanders-Brown Center on Aging, University of Kentucky College of Medicine, Lexington, KY, USA.ORCID 0000-0002-7980-2166
Amir H KashaniWilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0001-9767-7920
Joel H KramerDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Christian LachnerDepartment of Neurology, Mayo Clinic in Florida, Jacksonville, FL, USA.ORCID 0000-0002-1801-9768
Jin-Moo LeeMallinckrodt Institute of Radiology, Washington University in St Louis School of Medicine, St. Louis, MO, USA.ORCID 0000-0002-3979-0906
Peiying LiuDepartment of Diagnostic Radiology & Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.ORCID 0000-0003-0830-5960
Hanzhang LuDepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0003-3871-1564
Pauline MaillardDepartment of Neurology, University of California, Davis, Davis, CA, USA.ORCID 0000-0003-3516-6345
Ronald C PetersenDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-8178-6601
Bruce M PsatyCardiovascular Health Research Unit, Department of Medicine, Epidemiology, and Health Systems and Population, University of Washington, Seattle, WA, USA.ORCID 0000-0002-7278-2190
John M RingmanDepartment of Neurology, Alzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0001-5429-0777
Gary A RosenbergCenter for Memory and Aging, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.ORCID 0000-0001-7426-7064
Claudia L SatizabalGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health San Antonio, San Antonio, TX, USA.ORCID 0000-0002-1115-4430
Sean I SavitzInstitute for Stroke and Cerebrovascular Disease, The University of Texas Health Science Center, Houston, TX, USA.
Julie A SchneiderRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Sudha SeshadriGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health San Antonio, San Antonio, TX, USA.ORCID 0000-0001-6135-2622
Prashanthi VemuriDepartment of Radiology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0003-4286-0589
Danny J J WangDepartment of Neurology, Alzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0002-0840-7062
Donna M WilcockCenter for Neurodegenerative Disorders, IUSM/IUH Neuroscience Institute & Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0000-0003-3388-1564
B Gwen WindhamDepartment of Medicine, The MIND Center, University of Mississippi Medical Center, Jackson, MS, USA.
Rong ZhangDepartment of Neurology, UT Southwestern Medical Center, Dallas, TX, USA.
Carissa TuozzoDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0003-0946-076X
Herpreet SinghDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0003-3797-7301
Sue MoyDepartment of Radiology, Massachusetts General Hospital, Boston, MA, USA.
Vilma Okey-EwurumNeurological Clinical Research Institute, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-9001-4945
Courtney B PageDuke Clinical Research Institute, Durham, NC, USA.ORCID 0000-0001-7671-3355
Hillary MulderDuke Clinical Research Institute, Durham, NC, USA.ORCID 0000-0003-4838-582X
Pia KivisäkkDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0001-9708-7509
Deborah BlackerDepartment of Psychiatry, Mass. General Hospital/Harvard Medical School; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0001-6107-7376
Lidiya MazinaNeurological Clinical Research Institute, Massachusetts General Hospital, Boston, MA, USA.ORCID 0009-0003-7474-6024
Karl G HelmerDepartment of Radiology, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-5113-6843
Kristin SchwabDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Lisa M WruckDuke Clinical Research Institute, Durham, NC, USA.ORCID 0000-0003-1732-9067
Roderick A CorriveauDepartment of Neuroscience, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
MarkVCID2 Consortium

Funding

University of Kentucky Alzheimer's Disease Research CenterP30AG072946 · NIA · UNIVERSITY OF KENTUCKY · PI LINDA J VAN ELDIK · 2021 to 2026
$23.5M
VCID Biomarkers Coordinating CenterU24NS100591 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI Steven M Greenberg · 2016 to 2026
$19.8M
Washington University University of Texas Southwestern VCID Consortium SiteUF1NS125512 · NINDS · WASHINGTON UNIVERSITY · PI Hongyu An, Andria Lee Ford · 2021 to 2026
$6.3M
Validation of Biomarkers of Small Vessel Injury in VCIDUF1NS100598 · NINDS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI ROSENBERG, GARY ALLEN · 2021 to 2023
$6.3M
The University of Kentucky MarkVCID Biomarker Validation Cohort: Development of a Toolbox to Advance VCID Interventional StudiesUF1NS125488 · NINDS · UNIVERSITY OF KENTUCKY · PI JICHA, GREGORY A, WILCOCK, DONNA M · 2021 to 2023
$6.1M
MarkVCID Validation in the General CommunityUF1NS125417 · NINDS · MAYO CLINIC ROCHESTER · PI PETERSEN, RONALD C, VEMURI, PRASHANTHI · 2021 to 2023
$6.1M
Validation of Imaging and Blood-based Small Vessel VCID Biomarkers in Multiethnic PopulationUF1NS100614 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KASHANI, AMIR H, RINGMAN, JOHN M · 2021 to 2021
$2.6M
Validation of small vessel vascular contributions to cognitive impairment and dementia (VCID) biomarkersUF1NS100588 · NINDS · JOHNS HOPKINS UNIVERSITY · PI ALBERT, MARILYN S., LU, HANZHANG · 2021 to 2021
$2.6M
Novel Imaging and Biofluid Biomarkers of Small Vessel Cerebrovascular DiseaseUF1NS100608 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRAMER, JOEL H · 2021 to 2021
$2.5M
Longitudinal validation of cerebral small vessel disease biomarkers in diverse community-based older adults without dementiaUF1NS100599 · NINDS · RUSH UNIVERSITY MEDICAL CENTER · PI ARFANAKIS, KONSTANTINOS, SCHNEIDER, JULIE A. · 2021 to 2021
$2.5M
Multiethnic Validation of VCID biomarkers in South TexasUF1NS125513 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI FORNAGE, MYRIAM, SATIZABAL, CLAUDIA L · 2021 to 2021
$2.4M
Multimodal MRI biomarkers of small vessel disease for older persons with and without dementia.UH2NS100599 · NINDS · RUSH UNIVERSITY MEDICAL CENTER · PI ARFANAKIS, KONSTANTINOS, SCHNEIDER, JULIE A. · 2016 to 2017
$2.2M
NIA NIH HHS P30 AG072946NINDS NIH HHS U24 NS100591NINDS NIH HHS UF1 NS100588NINDS NIH HHS UF1 NS100598NINDS NIH HHS UF1 NS100599NINDS NIH HHS UF1 NS100608NINDS NIH HHS UF1 NS100614NINDS NIH HHS UF1 NS125417NINDS NIH HHS UF1 NS125488NINDS NIH HHS UF1 NS125512NINDS NIH HHS UF1 NS125513NINDS NIH HHS UH2 NS100599
6 · The paper itself

Abstract

objectiveTo 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.

methodsParticipants 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.

resultsMarkVCID2 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).

interpretationMarkVCID2 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.

Indexed as

Cerebral Small Vessel DiseasesCognitive DysfunctionAgedAged, 80 and overBiomarkersFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedRisk FactorsBiomarkers

Identifiers

PMID40977537
PMCPMC13126552

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