White Matter Hyperintensities Moderate the Association Between Diabetes and Non-AD Brain Atrophy
Authors' conclusion
Our 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.
Study context
- Population
- Individuals without dementia from two memory clinic-based cohorts: Harmonization (primary analysis; 112 diabetes, 284 controls) and Alzheimer's Disease Neuroimaging Initiative (ADNI) (secondary analysis; 64 diabetes, 600 controls)
- Exposure
- Diabetes vs control, and interaction of diabetes with white matter hyperintensities (WMHs)
- Outcome
- Interaction effect between diabetes and white matter hyperintensities (WMHs) on brain atrophy
Methodological detailstwo independent memory clinic-based cohorts, longitudinal
- Two independent memory clinic-based cohorts
- Longitudinal
Main finding
As reported in the abstract
Brain atrophy (Harmonization)
- Diabetes was not associated with brain atrophy cross-sectionally or longitudinally
- Significant cross-sectional interaction between diabetes and WMHs on brain atrophy in Harmonization, affecting cortical gray matter and the frontal lobe
Observational data: associations, not effects.
Further findings
Alzheimer disease (AD)-specific atrophy and adjustment for plasma pTau181
- No interactive effect for AD-specific atrophy; interactive effect remained significant after adjusting for plasma pTau181
Mediation of diabetes effect on cognition
- Cortical gray matter mediated the effect of diabetes on cognition at higher WMHs burden
Replication in ADNI
- Diabetes and WMHs interacted to accelerate brain atrophy over time
Original publication
White Matter Hyperintensities Moderate the Association Between Diabetes and Non-AD Brain Atrophy. Diabetes Care. Published 27 October 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →