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Combined Effect of Cerebral Hypoperfusion and White Matter Lesions on Executive Functioning – The SMART-MR Study

Background/Aims: It has been hypothesized that cerebral hypoperfusion may contribute to cognitive deterioration. Patients with white matter lesions (WML) may be more vulnerable to a decrease in cerebral blood flow (CBF) due to an impaired autoregulation. We investigated the association between CBF and cognitive performance and whether WML modified this relation. Methods: Within the SMART-MR study, a cohort study among patients with manifest arterial disease, cross-sectional analyses were performed in 472 patients (mean age 57 ± 10 years, 77% male). Total CBF was measured with magnetic resonance angiography in the internal carotid arteries and basilar artery, and was expressed per 100 ml brain volume. Neuropsychological tests assessing executive functioning and memory were performed and composite scores were calculated. We used linear regression analyses, adjusted for age, sex, education and intelligence, to investigate the association between CBF and cognitive performance. Results: We found that WML modified the association between CBF and executive functioning (p for interaction <0.001); the association between lower CBF and worse performance on executive functioning became stronger and significant with increasing volumes of WML. Lower CBF was not associated with worse memory. Conclusion: Our results suggest that a combination of lower CBF and WML may impair executive functioning but not memory.