Cognitive impairment in patients with diabetes has been linked to both vascular and neurodegenerative processes, but the contribution of small vessel disease to brain atrophy remains uncertain. A study published in the journal Diabetes Care analyzed two independent memory clinic–based cohorts of individuals without dementia to examine whether diabetes and white matter hyperintensities (WMHs) interact to influence brain atrophy and cognition.

The primary Harmonization cohort included 112 individuals with diabetes and 284 controls, while the secondary analysis from the Alzheimer's Disease Neuroimaging Initiative (ADNI) included 64 participants with diabetes and 600 controls. Participants underwent longitudinal brain magnetic resonance imaging (MRI), cognitive assessments, and plasma phosphorylated tau 181 (pTau181) measurement. WMHs and brain atrophy were quantified using cortical gray matter volume, frontal lobe measures, the Schwarz signature, the McEvoy signature, and hippocampal volume as Alzheimer disease (AD)-specific atrophy markers.

Findings

• Diabetes was not associated with brain atrophy in either cross-sectional or longitudinal analyses.
• A significant interaction between diabetes and WMHs was observed for cortical gray matter and frontal lobe atrophy in the Harmonization cohort.
• No significant interaction was identified for AD-specific atrophy measures, and the association remained significant after adjustment for plasma pTau181 levels.
• Cortical gray matter atrophy mediated the association between diabetes and cognition at higher WMH burden levels.
• Similar findings were replicated in the ADNI cohort, where diabetes and WMHs interacted to accelerate brain atrophy over time.

These results suggest that diabetes-associated cognitive impairment was primarily a vascular phenomenon rather than an accelerator of classic Alzheimer neurodegeneration.