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

Okl Hamilton,Sr Cox,L Ballerini,Me Bastin,J Corley,Aj Gow,S Muñoz Maniega,P Redmond,M Del C Valdés Hernández,Jm Wardlaw,Ij Deary

doi:10.1016/j.neurobiolaging.2021.04.007

Okl Hamilton, Sr Cox + Show 9 more

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https://doi.org/10.1016/j.neurobiolaging.2021.04.007

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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.

Highlights

Cerebral small vessel disease (SVD) is a leading cause of vascular cognitive impairment, contributing to multiple neurological disorders ranging from stroke, to mild cognitive impairment and dementia
The four marker variables had moderate to large loadings on the latent SVD variable, which accounted for 25% of the variance in white matter hyperintensities (WMH)/total intracranial volume (TIV), 10% of the variance in perivascular spaces (PVS), 32% of the variance in lacunes, and 18% of the variance in microbleeds
The latent variable representing total SVD burden accounted for 13% of the variance in general cognitive ability, 14% of the variance in processing speed, 7% of the variance in verbal memory, and 3% of the variance in visuospatial ability

Summary

Introduction

Cerebral small vessel disease (SVD) is a leading cause of vascular cognitive impairment, contributing to multiple neurological disorders ranging from stroke, to mild cognitive impairment and dementia. The majority of the literature examining SVD-related brain changes and cognitive ability focuses on individual radiological markers of SVD (most commonly WMH volume), fails to account for their potentially cumulative impact on cognitive performance. There is evidential support for considering the ‘total’ burden of SVD as a variable: different types of SVD lesions commonly occur together, are aetiologically related (Wardlaw et al, 2013), and associate with one another across a range of patient and healthy ageing populations (Ghaznawi et al, 2019, Potter et al, 2015). Ballerini et al / Neurobiology of Aging 105 (2021) 25–34

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