Associations between total MRI-visible small vessel disease burden and domain-specific cognitive abilities in a community-dwelling older-age cohort

Abstract

Cerebral small vessel disease (SVD) is a leading cause of vascular cognitive impairment, however the precise nature of SVD-related cognitive deficits, and their associations with structural brain changes, remain unclear. We combined computational volumes and visually-rated MRI markers of SVD to quantify total SVD burden, using data from the Lothian Birth Cohort 1936 (n = 540; age: 72.6 ± 0.7 years). We found negative associations between total SVD burden and general cognitive ability (standardized β: -0.363; 95%CI: [-0.49, -0.23]; p_(FDR) < 0.001), processing speed (-0.371 [-0.50, -0.24]; p_(FDR) < 0.001), verbal memory (-0.265; [-0.42, -0.11]; p_(FDR) = 0.002), and visuospatial ability (-0.170; [-0.32, -0.02]; p_(FDR) = 0.029). Only the association between SVD burden and processing speed remained after accounting for covariance with general cognitive ability (-0.325; [-0.61, -0.04]; p_(FDR) = 0.029). This suggests that SVD's association with poorer processing speed is not driven by, but is independent of its association with poorer general cognitive ability. Tests of processing speed may be particularly sensitive to the cognitive impact of SVD, but all major cognitive domains should be tested to determine the full range of SVD-related cognitive characteristics.

Keywords: Cerebral small vessel disease; Cerebrovascular disease; Cognitive aging; Magnetic resonance imaging; Vascular cognitive impairment; White matter hyperintensities.