Association of white matter hyperintensities and gray matter volume with cognition in older individuals without cognitive impairment.

Zoe Arvanitakis,Debra A Fleischman,Konstantinos Arfanakis,David A Bennett,Lisa L Barnes,Sue E Leurgans

doi:10.1007/s00429-015-1034-7

Abstract

Both presence of white matter hyperintensities (WMH) and smaller total gray matter volume on brain magnetic resonance imaging (MRI) are common findings in old age, and contribute to impaired cognition. We tested whether total WMH volume and gray matter volume had independent associations with cognition in community-dwelling individuals without dementia or mild cognitive impairment (MCI). We used data from participants of the Rush Memory and Aging Project. Brain MRI was available in 209 subjects without dementia or MCI (mean age 80; education = 15 years; 74 % women). WMH and gray matter were automatically segmented, and the total WMH and gray matter volumes were measured. Both MRI-derived measures were normalized by the intracranial volume. Cognitive data included composite measures of five different cognitive domains, based on 19 individual tests. Linear regression analyses, adjusted for age, sex, and education, were used to examine the relationship of logarithmically-transformed total WMH volume and of total gray matter volume to cognition. Larger total WMH volumes were associated with lower levels of perceptual speed (p < 0.001), but not with episodic memory, semantic memory, working memory, or visuospatial abilities (all p > 0.10). Smaller total gray matter volumes were associated with lower levels of perceptual speed (p = 0.013) and episodic memory (p = 0.001), but not with the other three cognitive domains (all p > 0.14). Larger total WMH volume was correlated with smaller total gray matter volume (p < 0.001). In a model with both MRI-derived measures included, the relation of WMH to perceptual speed remained significant (p < 0.001), while gray matter volumes were no longer related (p = 0.14). This study of older community-dwelling individuals without overt cognitive impairment suggests that the association of larger total WMH volume with lower perceptual speed is independent of total gray matter volume. These results help elucidate the pathological processes leading to lower cognitive function in aging.

Highlights

White matter hyperintensities (WMH) are brain white matter lesions with high signal on T2-weighted fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI)
This study examines the relation of total white matter hyperintensities (WMH) volume to cognitive function in different cognitive domains, and tests whether the relation is independent of total gray matter volume
Using voxel-wise multiple linear regression analyses controlling for total gray matter volume, we found that the presence of WMH in a number of periventricular areas was associated with a lower perceptual speed score (Fig. 3)

Summary

Introduction

White matter hyperintensities (WMH) are brain white matter lesions with high signal on T2-weighted fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI). These lesions are believed to represent underlying pathologic changes which are variable in nature and severity, including alterations in myelin and axon structure, gliosis, and small vessel disease (Gouw et al 2011). Few studies have systematically examined the relationship of WMH with a range of cognitive domains among older individuals without neurologic conditions or diseases, and results of these few studies are mixed, with data suggesting associations with some domains (e.g., executive function) but not others (Vannorsdall et al 2009; Murray et al 2010; Hedden et al 2012)

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