Abstract
Slowed processing speed is considered a hallmark feature of cognitive decline in cerebral small vessel disease (SVD); however, it is unclear whether SVD’s association with slowed processing might be due to its association with overall declining general cognitive ability. We quantified the total MRI-visible SVD burden of 540 members of the Lothian Birth Cohort 1936 (age: 72.6 ± 0.7 years; 47% female). Using latent growth curve modelling, we tested associations between total SVD burden at mean age 73 and changes in general cognitive ability, processing speed, verbal memory and visuospatial ability, measured at age 73, 76, 79 and 82. Covariates included age, sex, vascular risk and childhood cognitive ability. In the fully adjusted models, greater SVD burden was associated with greater declines in general cognitive ability (standardised β: −0.201; 95% CI: [−0.36, −0.04]; pFDR = 0.022) and processing speed (−0.222; [−0.40, −0.04]; pFDR = 0.022). SVD burden accounted for between 4 and 5% of variance in declines of general cognitive ability and processing speed. After accounting for the covariance between tests of processing speed and general cognitive ability, only SVD’s association with greater decline in general cognitive ability remained significant, prior to FDR correction (−0.222; [−0.39, −0.06]; p = 0.008; pFDR = 0.085). Our findings do not support the notion that SVD has a specific association with declining processing speed, independent of decline in general cognitive ability (which captures the variance shared across domains of cognitive ability). The association between SVD burden and declining general cognitive ability supports the notion of SVD as a diffuse, whole-brain disease and suggests that trials monitoring SVD-related cognitive changes should consider domain-specific changes in the context of overall, general cognitive decline.
Highlights
Cerebral small vessel disease (SVD) is a major cause of cognitive impairment in older adults
After accounting for the shared variance between domain-specific scores, only the association with processing speed remained. These findings suggest that the apparent associations we observed between SVD burden and domain-specific scores of verbal memory and visuospatial ability, were largely due to the confounding associations between SVD burden and general cognitive ability
In a sample of relatively healthy older individuals, we investigate associations between total MRI-visible SVD burden at age 73 and Translational Psychiatry (2021)11:376 longitudinal cognitive decline between the ages of 73 and 82, a 540 > 1 microbleed), both lacunes and microbleeds were modelled as period that coincides with a substantial increase in dementia risk binary outcomes
Summary
Cerebral small vessel disease (SVD) is a major cause of cognitive impairment in older adults. Caused by dysfunction of the brain’s arterioles, capillaries and venules, the downstream effects of SVD are visible on neuroimaging as white matter hyperintensities (WMH) and lacunes of presumed vascular origin, cerebral microbleeds and visible perivascular spaces (PVS; see Fig. 1) [3] In most individuals, these radiological markers do not result in overt clinical symptoms; their presence doubles the risk of stroke, and increases the risk of dementia and death in the general population [4]. Previous studies examining domain-specific cognitive decline in SVD have not accounted for the well-replicated phenomenon in psychological research that cognitive test scores typically correlate positively with one another, such that an individual who performs well on a given cognitive test, is likely to perform well on a broader range of tests [8] This common variance among test scores can be accounted for by general cognitive ability, often termed ‘g’. The association might be wholly accounted for by an association with general cognitive ability (on which all cognitive domains load substantially); second, the association might be partly with general cognitive ability and partly with the cognitive domain; and third, the association might
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