Association of type 2 diabetes with brain atrophy and cognitive impairment

Objective: We investigated the associations of diabetes and hypertension with imaging biomarkers (markers of neuronal injury and ischemic damage) and with cognition in a populationbased cohort without dementia. Methods: Participants (n 5 1,437, median age 80 years) were evaluated by a nurse and physician and underwent neuropsychological testing. A diagnosis of cognitively normal, mild cognitive impairment (MCI), or dementia was made by an expert panel. Participants underwent MRI to determine cortical and subcortical infarctions, white matter hyperintensity (WMH) volume, hippocampal volume (HV), and whole brain volume (WBV). The medical records were reviewed for diabetes and hypertension in midlife or later. Results: Midlife diabetes was associated with subcortical infarctions (odds ratio, 1.85 [95%confidence interval, 1.09-3.15]; p 5 0.02), reduced HV (24%[27 to 21.0]; p 5 0.01), reduced WBV (22.9% [24.1 to 21.6]), and prevalent MCI (odds ratio, 2.08; p 5 0.01). The association between diabetes and MCI persisted with adjustment for infarctions andWMH volume but was attenuated after adjustment for WBV (1.60 [0.87-2.95]; p 5 0.13) and HV (1.82 [1.00-3.32]; p 5 0.05). Midlife hypertension was associated with infarctions and WMH volume and was marginally associated with reduced performance in executive function. Effects of late-life onset of diabetes and hypertension were few. Conclusions: Midlife onset of diabetes may affect late-life cognition through loss of brain volume. Midlife hypertension may affect executive function through ischemic pathology. Late-life onset of these conditions had fewer effects on brain pathology and cognition.