Abstract

Introduction: Prior research has shown that an increased burden of white matter hyperintensity (WMH) is an independent risk factor for the development of dementia. However, research has not focused specifically on stroke survivors, who are also predisposed to dementia. Methods: This is a secondary analysis of patients in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial, who had a lacunar ischemic stroke within 6 months of enrollment and an MRI at study baseline. The primary outcome is change in the Cognitive Abilities Screening Instrument (CASI) from baseline to a 12 month follow-up. The primary predictor is the Fazekas score on the baseline MRI, with the scores of 0 and 1 collapsed to balance the cohort. We fit regression models to the 12 month CASI and adjusted for baseline CASI, patient age, gender, white race, Barthel Index score at 3 months from enrollment, college education, employment status, diabetes, COPD, and SPS3 randomization arm. Results: We included 2,413 patients with a mean (SD) age of 62.8 (10.6) years and 63.7% were male. There were 946 patients in Fazekas 0-1, 1,009 in Fazekas 2, and 458 in Fazekas 3. The mean (SD) CASI score at baseline and 12 months were 85.3 (12.4) and 86.0 (12.4). In the adjusted linear regression model, compared to a baseline Fazekas of 0-1, a baseline Fazekas of 2 was associated with a worse cognitive score (β coef = -0.55, 95% CI -1.01, -0.08, p=0.020), as was Fazekas of 3 (β coef = -0.76, 95% CI -1.36, -0.16, p=0.013). Conclusion: In patients with recent lacunar stroke, an increased baseline WMH burden is a risk factor for worse performance over a one year period on a validated test of global cognition. Although the absolute difference in score that we found was small (~0.5-0.8 points), this difference is over one year and, over years to decades, could become clinically significant. The implication of this finding is that lacunar ischemic stroke has additive cognitive consequences for patients with an established WMH burden, suggesting that primary stroke prevention in patients with WMH could be an important public health goal to reduce the burden of dementia.

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