Diabetes and white matter hyperintensities (WMHs) appear to act together to drive brain atrophy and cognitive decline, independent of Alzheimer’s disease processes. The study, published in Diabetes Care, provides new insight into cerebrovascular contributions to diabetes-related cognitive impairment.

The analysis included individuals without dementia from two memory clinic–based cohorts: Harmonization (112 with diabetes, 284 controls) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (64 with diabetes, 600 controls). All participants underwent brain MRI, cognitive testing, and plasma phosphorylated tau (pTau181) assessment.

While diabetes alone was not associated with brain atrophy, significant interaction effects with WMHs were seen in cortical gray matter and the frontal lobe. These associations persisted after adjustment for pTau181, suggesting that Alzheimer pathology did not explain the findings. Alzheimer-specific atrophy markers, including the Schwarz and McEvoy signatures and hippocampal volume, showed no correlation.

Cortical gray matter mediated the relationship between diabetes and cognitive decline among those with greater WMH burden. Replication in the ADNI cohort confirmed that diabetes and WMHs jointly accelerate brain volume loss over time.