Evidence mapPaperPMID 40735976Full record

ArticleAnnals of neurology2025

Frequency of Microvascular Pathology and Hippocampal Atrophy on Magnetic Resonance Imaging in a Community Study of Alzheimer's Disease with Blood-Based Biomarkers.

Tamil Iniyan Gunasekaran, Danurys Sanchez, Dolly Reyes-Dumeyer, Rabel Ventura, Clarissa Morales, Mohamad Alshikho, Annie J Lee, Rafael A Lantigua, Yian Gu, Lawrence S Honig and 3 more

Abstract read
In one paragraph

Article in Annals of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

13 authors.

Tamil Iniyan GunasekaranTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Danurys SanchezTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Dolly Reyes-DumeyerTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Rabel VenturaG.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.ORCID 0000-0002-2674-2235
Clarissa MoralesTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Mohamad AlshikhoTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Annie J LeeG.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Rafael A LantiguaTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Yian GuTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.ORCID 0000-0002-4297-1548
Lawrence S HonigTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Badri N VardarajanTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Adam M BrickmanTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Richard MayeuxTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.ORCID 0000-0001-6519-9696

Funding

Clinical and Translational Science AwardUL1TR001873 · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2025 to 2025
$10.0M
Research Education CoreP30AG066462 · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2025 to 2025
$4.8M
Epidemiological and Genetic Investigations of Blood-Based Biomarkers for Alzheimer's Disease in the Multiethnic, Washington Heights, Inwood, Columbia Aging Project (WHICAP)R01AG072474 · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2025 to 2025
$2.2M
Genetic Association Between Alzheimer's Disease and Cardio-Cerebrovascular Risk FactorsK01AG084849 · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2025 to 2025
$126k
NCATS NIH HHS UL1 TR001873NIA NIH HHS K01 AG084849NIA NIH HHS P30 AG066462NIA NIH HHS R01 AG066107NIA NIH HHS R01 AG072474NIA NIH HHS RF1 AG066107
6 · The paper itself

Abstract

objectiveBlood-based biomarkers for Alzheimer's disease (AD), representing antemortem indicators of AD pathophysiology, have greatly improved the accuracy of diagnosis. However, these biomarkers may not capture a frequent coincident pathology, such as cerebrovascular disease.

methodsWe measured plasma amyloid-β40, amyloid-β42, total tau, tau phosphorylated at threonine 181, tau phosphorylated at threonine 217, glial fibrillary acidic protein, and neurofilament light chain in 685 multiancestral individuals who had clinical assessments and brain magnetic resonance imaging. The cohort was represented by individuals of European, African American, and Caribbean Hispanic ancestry. Participants were then classified as biomarker-positive or -negative for AD based on previously established cutoffs: 2.65 pg/mL for, tau phosphorylated at threonine 181 and 0.39 pg/mL for tau phosphorylated at threonine 217. We used magnetic resonance images to compare white matter hyperintensity volume (WMH), silent brain infarcts, microhemorrhages, and hippocampus volume across groups by their clinical diagnosis and biomarker status.

resultsIn the P-tau181 group (n = 685), 70 individuals (10.2%) had dementia or amnestic mild cognitive impairment. A total of 40 (57%) were biomarker-positive for AD, and 30 were classified as other dementia. Among 615 without dementia, 265 (40.3%) were preclinical AD, and 348 (50.8%) were biomarker-negative controls. In the tau phosphorylated at threonine 217 group (n = 535), 54 (10.1%) had dementia or amnestic mild cognitive impairment, including 33 biomarker-positive for AD and 21 with other dementia, whereas 183 (38.0%) were preclinical AD and 298 (61.9%) were biomarker-negative controls. Across both classifications, biomarker-positive for AD and other dementia individuals showed greater WMH volumes, more infarcts, and smaller hippocampus. However, P-tau217 positivity was more sensitive to WMH volume differences, whereas tau phosphorylated at threonine 181 better captured hippocampal atrophy and silent brain infarcts. Interestingly, ethnic differences may also influence detection of changes in WMH volumes, hippocampal volume, and infarcts in relation to specific biomarkers.

interpretationThe results indicate that cerebrovascular disease is consistently involved in dementia either directly or as a coincident pathology in AD. These results underscore the need to incorporate both blood-based biomarkers and structural imaging in the evaluation of patients with dementia. ANN NEUROL 2025;98:1027-1043.

Indexed as

Alzheimer DiseaseHippocampusMicrovesselsAgedAged, 80 and overAmyloid beta-PeptidesAtrophyBiomarkersCohort StudiesFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedNeurofilament ProteinsPeptide FragmentsAmyloid beta-PeptidesBiomarkersNeurofilament ProteinsPeptide Fragmentstau Proteins

Identifiers

PMID40735976
PMCPMC12577681

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.