Evidence map›Paper›PMID 40465677›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Assessing the Global Impact of Brain Small Vessel Disease on Cognition: The Multi-Ethnic Study of Atherosclerosis.

Sokratis Charisis, Tanweer Rashid, Christina Dintica, Mitzi Gonzales, Hangfan Liu, Jeffrey B Ware, Thomas R Austin, Paul N Jensen, Alison E Fohner, Jordan E Tanley and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
–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

8 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Advancing global dementia research through equity and inclusion.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
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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

25 authors.

Sokratis CharisisNeuroimage Analytics Laboratory (NAL) and the Biggs Institute Neuroimaging Core (BINC), Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center San Antonio, San Antonio, Texas, USA.ORCID 0000-0001-6578-393X
Tanweer RashidNeuroimage Analytics Laboratory (NAL) and the Biggs Institute Neuroimaging Core (BINC), Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center San Antonio, San Antonio, Texas, USA.
Christina DinticaDepartment of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, California, USA.
Mitzi GonzalesDepartment of Neurology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Hangfan LiuNeuroimage Analytics Laboratory (NAL) and the Biggs Institute Neuroimaging Core (BINC), Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center San Antonio, San Antonio, Texas, USA.
Jeffrey B WareDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Thomas R AustinDepartment of Epidemiology, University of Washington, Seattle, Washington, USA.
Paul N JensenCardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA.
Alison E FohnerDepartment of Epidemiology, University of Washington, Seattle, Washington, USA.
Jordan E TanleyDepartment of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Jingzhong DingDepartment of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
José A LuchsingerDepartments of Medicine and Epidemiology, Columbia University Medical Center, New York, New York, USA.
Bonnie SachsDepartment of Neurology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Ilya M NasrallahDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
R Nick BryanDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Kathleen M HaydenDepartment of Social Sciences and Health Policy, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
David WolkAlzheimer's Disease Research Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Katya RascovskyDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Christos DavatzikosDepartment of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
William T LongstrethDepartment of Epidemiology, University of Washington, Seattle, Washington, USA.
Kristine YaffeDepartment of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, California, USA.
Sudha SeshadriNeuroimage Analytics Laboratory (NAL) and the Biggs Institute Neuroimaging Core (BINC), Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center San Antonio, San Antonio, Texas, USA.
Susan R HeckbertDepartment of Epidemiology, University of Washington, Seattle, Washington, USA.
Timothy HughesDepartment of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Mohamad HabesNeuroimage Analytics Laboratory (NAL) and the Biggs Institute Neuroimaging Core (BINC), Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center San Antonio, San Antonio, Texas, USA.ORCID 0000-0001-9447-5805

Funding

MVP Data Integration into the ADSP Phenotype Harmonization ConsortiumU24AG074855 · NIA · VANDERBILT UNIVERSITY MEDICAL CENTER · PI CUCCARO, MICHAEL L, HOHMAN, TIMOTHY J · 2021 to 2025
$37.5M
Subclinical Vascular Contributions to Alzheimer's Disease: The Multi-Ethnic Study of Atherosclerosis (MESA) Multisite Study of AD (Renewal)R01AG058969 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Timothy M. Hughes, YONGMEI LIU · 2018 to 2026
$33.4M
South Texas Alzheimer's Disease Research CenterP30AG066546 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Meredith Nahm Zozus · 2021 to 2026
$24.0M
Task Area A Core Study Operations.Task Area A shall encompass annual follow-up of cohort members, clinical endpoints ascertainment, study coordination activities, maintenance of the database and biosp75N92020D00001 · NHLBI · UNIVERSITY OF WASHINGTON · PI MCCLELLAND, ROBYN LEAGH · 2020 to 2025
$17.2M
Atrial fibrillation burden, vascular disease of the brain and cardiac MRI in MESAR01HL127659 · NHLBI · UNIVERSITY OF WASHINGTON · PI HECKBERT, SUSAN R · 2015 to 2018
$7.4M
Cerebral tau deposition and comorbid cerebrovascular disease across the Alzheimer's disease continuum in Mexican AmericansR01AG085571 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI GONZALES, MITZI MICHELLE, HABES, MOHAMAD · 2024 to 2025
$5.7M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00005 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WATSON, KAROL E · 2020 to 2025
$5.1M
TO EXERCISE OPTION PERIOD ONE (1) FOR TASK AREA A - MESA CORE OPERATIONS, FIELD CENTER.75N92020D00004 · NHLBI · NORTHWESTERN UNIVERSITY · PI SIEGEL, JONATHAN H · 2020 to 2025
$4.5M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00006 · NHLBI · UNIVERSITY OF MINNESOTA · PI PANKOW, JAMES S · 2020 to 2025
$4.4M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00003 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI POST, WENDY S · 2020 to 2025
$3.8M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00007 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI BERTONI, ALAIN GERALD · 2020 to 2025
$3.5M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00002 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SHEA, STEVEN J · 2020 to 2025
$3.4M
NCATS NIH HHS UL1-TR-000040NCATS NIH HHS UL1-TR-001079NCATS NIH HHS UL1-TR-001420NHLBI NIH HHS 75N92020D00001NHLBI NIH HHS 75N92020D00002NHLBI NIH HHS 75N92020D00003NHLBI NIH HHS 75N92020D00004NHLBI NIH HHS 75N92020D00005NHLBI NIH HHS 75N92020D00006NHLBI NIH HHS 75N92020D00007NHLBI NIH HHS HHSN268201500003INHLBI NIH HHS N01-HC-95159NHLBI NIH HHS N01-HC-95160NHLBI NIH HHS N01-HC-95161NHLBI NIH HHS N01-HC-95162NHLBI NIH HHS N01-HC-95163NHLBI NIH HHS N01-HC-95164NHLBI NIH HHS N01-HC-95165NHLBI NIH HHS N01-HC-95166NHLBI NIH HHS N01-HC-95167NHLBI NIH HHS N01-HC-95168NHLBI NIH HHS N01-HC-95169NHLBI NIH HHS R01 HL127659NIA NIH HHS R01 AG058969NIA NIH HHS R01 AG068629NIA NIH HHS R01 AG080821NIA NIH HHS R01 AG083865NIA NIH HHS R01 AG085571NIA NIH HHS U24 AG074855NIH HHS 1R01AG080821NIH HHS 1R01AG085571NIH HHS 1U24AG074855NIH HHS 5R01AG080821NIH HHS 5R01AG083865NIH HHS K24AG045334NIH HHS P30AG066546San Antonio Medical Foundation 1000003860
6 · The paper itself

Abstract

introductionWe aimed to examine the global impact of brain small vessel disease (SVD) on cognitive performance.

methodsIn 892 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), we derived perivascular spaces (PVS), white matter hyperintensities (WMH), microbleeds (MB), and white matter fractional anisotropy (FA) and trace (TR). Cognitive function was assessed with a comprehensive neuropsychological battery.

resultsA composite SVD measure was constructed as a linear combination of basal ganglia PVS, thalamus PVS, periventricular WMH, subcortical WMH, and white matter FA and TR, and exhibited associations with worse global and domain-specific cognitive performance. Additionally, SVD mediated the effect of age and cardiovascular disease risk on global cognitive function, both directly and through smaller gray matter (GM) volume. DISCUSSION: Integrating multiple individual SVD endophenotypes may more accurately reflect the neurobiology of SVD and capture its global impact on cognition. SVD mediates the effects of age and cardiovascular disease risk on cognition through both atrophy-related and non-atrophy-related pathways. HIGHLIGHTS: Associations between individual magnetic resonance imaging (MRI) markers of brain small vessel disease and cognitive outcomes might not fully capture the global impact of small vessel disease on cognition. We modeled small vessel disease as a latent construct, integrating multiple MRI endophenotypes in strategic brain regions. The small vessel disease construct was associated with worse global and domain-specific cognitive performance. The small vessel disease construct exhibited mediating effects in the relationships of aging and cardiovascular disease risk with cognition through pathways that both involve and are independent of brain atrophy. Integrating information from multiple relevant imaging endophenotypes could open new avenues in small vessel disease research, broadening our understanding of its risk factors and clinical correlates.

Indexed as

AtherosclerosisBrainCerebral Small Vessel DiseasesCognitionAgedAged, 80 and overEthnicityFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedNeuropsychological TestsWhite Matteragingatrophyattentioncardiovascular disease riskcerebral small vessel diseasecognitioncognitive performancedeep learningdelayed memorydiffusion tensor imagingenlarged perivascular spacesexecutive functionfactor analysisfractional anisotropyFramingham risk scoreglobal cognitiongray matter volumeimmediate memorylanguagelatent variablemagnetic resonance imagingmediationmicrobleedsphonemic fluencyprocessing speedsemantic fluencystructural equation modelingtracevisuospatial functioningwhite matter hyperintensities

Identifiers

PMID40465677
PMCPMC12136095

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.