Evidence map›Paper›PMID 42619937›Full record

ArticlemedRxiv : the preprint server for health sciences2026

Altered T1w/T2w-FLAIR Ratio in White Matter Hyperintensities as an Indicator of Structural Integrity Loss: Association with Alzheimer's Disease and Vascular Dementia.

Rushil Srirambhatla, Jacques-Yves Campion, Thomas Desmidt, Yiyan Pan, Carmen Andreescu, Pamela C L Ferreira, Guilherme Povala, Bruna Bellaver, João Pedro Ferrari-Souza, Douglas T Leffa and 20 more

Abstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

The trial behind it

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3 · Its place in the literature

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4 · The record

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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

30 authors.

Rushil SrirambhatlaDepartment of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, USA.ORCID 0009-0000-3362-7879
Jacques-Yves CampionUniversité de Tours, INSERM, Imaging Brain & Neuropsychiatry iBraiN U1253, 37032, Tours, France.
Thomas DesmidtUniversité de Tours, INSERM, Imaging Brain & Neuropsychiatry iBraiN U1253, 37032, Tours, France.
Yiyan PanDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Carmen AndreescuDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Pamela C L FerreiraDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Guilherme PovalaDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Bruna BellaverDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
João Pedro Ferrari-SouzaGraduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Douglas T LeffaDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Firoza Z LussierDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Marina Scop MedeirosDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Emma RuppertDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Francieli RohdenDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Chang Hyung HongDepartment of Psychiatry, Ajou University School of Medicine, Suwon, Republic of Korea (South Korea).
Hyun Woong RohDepartment of Psychiatry, Ajou University School of Medicine, Suwon, Republic of Korea (South Korea).
Bumhee ParkDepartment of Biomedical Informatics, Ajou University School of Medicine, Suwon Republic of Korea (South Korea).
Jin Wook ChoiDepartment of Radiology, Ajou University School of Medicine, Seoul, South Korea.
Sang Won SeoDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (South Korea).
Seong Hye ChoiDepartment of Neurology, Inha University School of Medicine, Incheon, Republic of Korea (South Korea).
So Young MoonDepartment of Neurology, Ajou University School of Medicine, Suwon, Republic of Korea (South Korea).
Eun-Joo KimDepartment of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan, Republic of Korea (South Korea).
Byeong C KimDepartment of Neurology, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju, Republic of Korea (South Korea).
Young-Sil AnDepartment of Nuclear Medicine and Molecular Imaging, Ajou University School of Medicine, Republic of Korea (South Korea).
Yong Hyuk ChoDepartment of Psychiatry, Ajou University School of Medicine, Suwon, Republic of Korea (South Korea).
Sunhwa HongDepartment of Psychiatry, Ajou University School of Medicine, Suwon, Republic of Korea (South Korea).
Thomas K KarikariDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Tharick A PascoalDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Sang Joon SonDepartment of Psychiatry, Ajou University School of Medicine, Suwon, Republic of Korea (South Korea).
Helmet T KarimDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Funding

Vascular Moderators of the Impact of Alzheimer's Pathology in the Young-OldP01AG025204 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Milos D Ikonomovic · 2005 to 2026
$56.5M
Longitudinal multicenter head-to-head harmonization of tau PET tracersR01AG073267 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BAKER, SUZANNE L, PASCOAL, THARICK · 2021 to 2025
$41.1M
Research Education ComponentP30AG066468 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HOWARD J AIZENSTEIN · 2020 to 2026
$29.4M
Investigating Gains in Neurocognition in an Intervention Trial of Exercise SupplementR01AG053952 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BURNS, JEFFREY MURRAY, ERICKSON, KIRK I · 2016 to 2020
$27.5M
Mild Cognitive Impairment: A Prospective Community StudyR37AG023651 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Carmen Andreescu, MARY GANGULI · 2021 to 2026
$18.2M
Plasma brain-derived tau: a novel Alzheimer’s disease-type neurodegeneration biomarker with potential to complete the AT(N) scheme in bloodR01AG083874 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Thomas K Karikari · 2023 to 2026
$14.5M
Predictors of Altered CNS Structure, Function, and Connectomics in the Elderly using a Health Disparities FrameworkR01AG072641 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ann D. Cohen · 2022 to 2026
$9.6M
Subclinical vascular disease and AD pathology in the transition from midlife to old ageRF1AG052525 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LOPEZ, OSCAR L., REIS, STEVEN E · 2018 to 2018
$9.3M
Roles of Gray Matter Brain Aging and Small Vessel Disease in AD PathophysiologyRF1AG025516 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI AIZENSTEIN, HOWARD J, VILLEMAGNE, VICTOR LUIS · 2014 to 2021
$9.0M
Alzheimer Diagnosis in older Adults with Chronic Conditions ADACC NetworkU24AG082930 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Nicole R. Fowler, Thomas K Karikari · 2023 to 2026
$7.3M
Head-to-head comparisons of high-performance plasma phospho-tau epitopes for the detection of Alzheimer's diseaseR01AG075336 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Tharick Pascoal · 2022 to 2026
$3.7M
NIA NIH HHS P01 AG025204NIA NIH HHS P30 AG066468NIA NIH HHS R01 AG053952NIA NIH HHS R01 AG072641NIA NIH HHS R01 AG073267NIA NIH HHS R01 AG075336NIA NIH HHS R01 AG083874NIA NIH HHS R37 AG023651NIA NIH HHS RF1 AG025516NIA NIH HHS RF1 AG052525NIA NIH HHS U24 AG082930
6 · The paper itself

Abstract

Background: White matter hyperintensities (WMH) are prevalent in dementia, but lesion volume does not capture their microstructural heterogeneity. The T1-weighted to fluid-attenuated inversion recovery (T1w/T2w-FLAIR) ratio is sensitive to myelin, gliosis, and tissue water. We tested whether lesion-specific T1w/T2w-FLAIR ratio, referenced to each participanťs normal-appearing white matter (NAWM), differs by diagnosis and reflects distinct amyloid and vascular mechanisms in Alzheimer's disease (AD) and vascular dementia (VD). Methods: We analyzed 576 participants from the multicentre BICWALZS cohort (seven South Korean sites), spanning subjective cognitive impairment (SCI, n=71), mild cognitive impairment (n=270), AD (n=125) and VD (n=88). WMH T1w/T2w-FLAIR ratio was regressed on NAWM ratio, yielding standardized residuals as the outcome. Regression and mediation models tested diagnosis, plasma biomarkers, APOE genotype, amyloid PET and vascular risk burden, adjusting for age, sex, education and site. We conducted regression and mediation analyses after multiple imputation for missing variables. We adjusted for hierarchical models using Bonferroni correction. We tested for insensitivity to site effects by applying ComBat harmonization. Results: Older age, AD, VD, and high vascular risk burden were associated with higher residualized T1w/T2w-FLAIR ratios relative to SCI. Lower plasma amyloid-beta 42 (greater amyloid burden) was associated with lower T1w/T2w-FLAIR ratios. Greater vascular burden was associated with greater T1w/T2w-FLAIR ratios, which partially mediated the VD association with T1w/T2w-FLAIR. Lower amyloid-beta 42 (greater amyloid) was associated with lower T1w/T2w-FLAIR, which partially mediated the effect between AD and T1w/T2w-FLAIR ratio. Findings were robust to harmonization. Conclusions: Residualized WMH T1w/T2w-FLAIR ratio captures lesion-specific microstructural variation missed by volumetric measures, consistent with vascular-gliotic injury in VD and coexisting amyloid-linked demyelination in AD. Limitations include the cross-sectional design, no cognitively normal comparison group, and a predominantly Korean sample.

Indexed as

Alzheimer’s diseaseDementiaT1w/T2w-FLAIR ratiovascular dementiawhite matterWMH

Identifiers

PMID42619937
PMCPMC13484326

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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 OpenQuestion graph.