Early cerebral small vessel disease and brain volume, cognition, and gait

Abstract

Objective: Decline in cognitive function begins by the 40s, and may be related to future dementia risk. We used data from a community-representative study to determine whether there are age-related differences in simple cognitive and gait tests by the 40s, and whether these differences were associated with covert cerebrovascular disease on magnetic resonance imaging (MRI).

Methods: Between 2010 and 2012, 803 participants aged 40 to 75 years in the Prospective Urban Rural Epidemiological (PURE) study, recruited from prespecified postal code regions centered on 4 Canadian cities, underwent brain MRI and simple tests of cognition and gait as part of a substudy (PURE-MIND).

Results: Mean age was 58 ± 8 years. Linear decreases in performance on the Montreal Cognitive Assessment, Digit Symbol Substitution Test (DSST), and Timed Up and Go test of gait were seen with each age decade from the 40s to the 70s. Silent brain infarcts were observed in 3% of 40- to 49-year-olds, with increasing prevalence up to 18.9% in 70-year-olds. Silent brain infarcts were associated with slower timed gait and lower volume of supratentorial white matter. Higher volume of supratentorial MRI white matter hyperintensity was associated with slower timed gait and worse performance on DSST, and lower volumes of the supratentorial cortex and white matter, and cerebellum.

Interpretation: Covert cerebrovascular disease and its consequences on cognitive and gait performance and brain atrophy are manifest in some clinically asymptomatic persons as early as the 5th decade of life.

© 2015 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Figures

FIGURE 1

Distribution of magnetic resonance imaging white matter hyperintensity (WMH) by age decade. Red-to-yellow color indicates the probability of WMH at that location.

FIGURE 2

Brain regions where age was associated with cortical thickness. Advanced age was associated with decreased cortical thickness in many brain regions, most significantly in the superior frontal gyrus, inferior frontal gyrus, posterior superior and middle temporal gyri, precuneus, and supramarginal and inferior parietal cortex. Primary motor and sensory areas and the medial temporal lobe were less strongly associated with age, and there were small regions of anterior cingulate cortex and medial orbitofrontal cortex where advanced age was associated with increased cortical thickness. The color bar indicates the t value for the association; blue colors indicate regions of negative association (ie, where cortical thickness was lower in older subjects) and red–yellow colors indicate regions of positive association (ie, where cortical thickness was higher in older subjects).The false discovery rate method with alpha = 0.05 was used to correct for multiple comparisons.

FIGURE 3

Brain regions where white matter hyperintensity (WMH) is associated with cortical thickness. Higher WMH volume is associated with decreased cortical thickness in the superior parieto-occipital cortex and in the lingual gyrus of the left hemisphere only. The false discovery rate method was used to correct for multiple comparisons, with alpha set at 0.01 to account for comparisons with the 3 manifestations of small vessel disease analyzed (WMH, silent brain infarcts, and microbleeds). Average cortical thickness was not associated with silent brain infarcts or microbleeds.