Evidence map›Paper›PMID 41144252›Full record

ArticleDiabetes care2026

White Matter Hyperintensities Moderate the Association Between Diabetes and Non-AD Brain Atrophy.

Jiangbo Cui, Zhaojun Liu, Wei Ying Tan, Joyce R Chong, Shin Hui On, Eddie Jun Yi Chong, Narayanaswamy Venketasubramanian, Mitchell K P Lai, Christopher Chen, Saima Hilal and 1 more

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Article in Diabetes care, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Jiangbo CuiDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.ORCID 0000-0003-4403-4248
Zhaojun LiuDepartment of Rehabilitation Medicine, China-Japan Friendship Hospital, Beijing, China.
Wei Ying TanSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
Joyce R ChongDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Shin Hui OnDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Eddie Jun Yi ChongDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Narayanaswamy VenketasubramanianRaffles Neuroscience Centre, Raffles Hospital, Singapore, Singapore.
Mitchell K P LaiDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Christopher ChenDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Saima HilalDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.ORCID 0000-0001-5434-5635
Alzheimer’s Disease Neuroimaging Initiative

Funding

Ministry of Education A-0006106-00-00National Medical Research Council of Singapore A-0006310-00-00National Medical Research Council of Singapore MOH-000707-00National Medical Research Council of Singapore NMRC/CIRG/1446/2016National Medical Research Council of Singapore NMRC/CIRG/1485/2018National Medical Research Council of Singapore NMRC/CSA-SI/0007/2016
6 · The paper itself

Abstract

objectiveWhite matter hyperintensities (WMHs) moderate the association between diabetes and cognition, but the underlying mechanisms remain unknown. This study investigated the interaction effect between diabetes and WMHs on brain atrophy, the resulting atrophy patterns, and whether brain atrophy mediates the effect of diabetes on cognition. RESEARCH DESIGN AND

methodsThis study included individuals without dementia from two independent memory clinic-based cohorts: Harmonization (primary analysis, n = 112 case subjects with diabetes, n = 284 control subjects) and Alzheimer's Disease Neuroimaging Initiative (ADNI) (secondary analysis, n = 64 case subjects with diabetes, n = 600 control subjects). Participants underwent longitudinal brain MRI and cognitive assessments, along with plasma pTau181 measurement as a marker of Alzheimer disease (AD). WMHs and brain atrophy were quantified, with Schwarz signature, McEvoy signature, and hippocampal volume used as AD-specific atrophy measures.

resultsDiabetes was not associated with brain atrophy cross-sectionally or longitudinally. Instead, an interactive effect between diabetes and WMHs on brain atrophy was observed. In Harmonization, this interaction was significant in cross-sectional analyses, affecting cortical gray matter and the frontal lobe. No interactive effect was found for AD-specific atrophy, and the observed interactive effect remained significant after adjusting for plasma pTau181. Cortical gray matter mediated the effect of diabetes on cognition at higher WMHs burden. These results were replicated in ADNI, where diabetes and WMHs interacted to accelerate brain atrophy over time.

conclusionsOur study demonstrated diabetes and WMHs synergistically contribute to brain atrophy independent of AD, suggesting diabetes-associated cognitive impairment is primarily driven by cerebrovascular disease rather than Alzheimer pathology.

Indexed as

BrainDiabetes MellitusWhite MatterAgedAged, 80 and overAlzheimer DiseaseAtrophyCross-Sectional StudiesFemaleHumansMagnetic Resonance ImagingMale

Identifiers

PMID41144252

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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.