Abstract

Introduction: Retrospective and epidemiological studies have shown that white matter hyperintensity (WMH) is associated with vascular dementia, but WMH progression on serial MRIs has not been examined in a prospective study of diabetic patients, who have a higher risk of the adverse outcomes associated with WMH including dementia. Methods: This is a secondary analysis of the Memory in Diabetes (MIND) substudy of the Action to Control Cardiovascular Risk in Diabetes Follow-on Study (ACCORDION). The primary outcome was 4 cognitive tests measured at a baseline visit and month 80 follow-up visit, including Rey’s Auditory Verbal Learning Test (RAVLT), Mini Mental Status Examination (MMSE), Stroop test, and Digit Symbol Coding (DSC). The primary predictor was WMH progression, represented as the WMH volume on the month 80 MRI with the baseline WMH volume included in the model. We predicted change in the cognitive scores by modelling their association with WMH progression. Results: We included 262 patients, with a mean (SD) baseline age of 62.7 (5.3) years and 56.1% male. The mean (SD) WMH volume on the baseline and month 80 MRIs was 1.9 (3.0) and 4.3 (6.0) mL, respectively. The change in WMH was significantly associated with the change in RAVLT score in the linear regression model (β Coef -0.132, p=0.029). (Table). The mean (SD) RAVLT at baseline and month 80 was 8.0 (2.4) and 8.5 (2.8). Conclusions: WMH progression in diabetic patients is associated with worse performance on memory testing over an 80 month period. Though preliminary and not able to account for location of WMH, our results are consistent with the hypothesis that WMH progression is harmful to cognition in diabetics. The SPRINT MIND trial recently reported that intensive blood pressure control attenuates WMH progression and development of mild cognitive impairment, but excluded patients with diabetes. Against this backdrop, our data suggest that diabetics should be included in future trials to reduce WMH progression.

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