Cortical thickness is associated with gait disturbances in cerebral small vessel disease

Abstract

Although gait disturbances are present in a substantial portion of patients with cerebral small vessel disease (SVD), their pathogenesis has not been clarified as they are not entirely explained by the white matter lesions (WMLs) and lacunar infarcts. The role of cortical thickness in these patients remains largely unknown. We aimed to assess the regions of cortical thickness associated with distinct gait parameters in patients with SVD, and whether these associations were dependent on WMLs and lacunar infarcts. MRI data were obtained from 415 subjects with SVD, aged between 50 and 85 years. We assessed cortical thickness using surface-based cortical thickness analysis, and gait performance using the GAITRite system. Cortical thickness of predominantly the orbitofrontal and ventrolateral prefrontal cortex, the inferior parietal lobe, cingulate areas and visual association cortices was positively related to stride length. Thickness of the primary and supplementary motor cortices and the cingulate cortex was positively related to cadence, while thickness of the orbitofrontal and ventrolateral prefrontal cortex, anterior cingulate cortex and especially the inferior parietal lobe and superior temporal gyrus was negatively related to stride width. The associations with stride length and width were partially explained by the subcortical WMLs and lacunar infarcts. Cortical thickness may therefore be important in gait disturbances in individuals with SVD, with different cortical patterns for specific gait parameters. We suggest that cortical atrophy is part of the disease processes in patients with SVD.

Introduction

Cerebral small vessel disease (SVD), including white matter lesions (WMLs) and lacunar infarcts, is very common in elderly persons (de Leeuw et al., 2001). SVD is not only associated with cognitive impairment but also with gait disturbances (de Laat et al., 2010), an often neglected, but nevertheless important consequence of SVD. However, the anatomical and pathophysiological mechanisms underlying these gait disturbances in SVD remain poorly understood. WMLs and lacunar infarcts have been found to be important factors (de Laat et al., 2010). A number of studies have furthermore demonstrated that measures of global cerebral atrophy are strongly and independently related to these gait disturbances (Briley et al., 1997, Rosano et al., 2007, Rosano et al., 2008, Rosano et al., 2010).

Less is known about the specific role of cortical atrophy in gait disturbances in individuals with SVD, its spatial distribution and association with subcortical WMLs and lacunar infarcts. Only two studies have investigated the relationship between cortical atrophy and gait performance (Rosano et al., 2007, Rosano et al., 2008). Using volumetric morphometry, they found that cortical volume in some frontoparietal regions was positively related to gait performance. An alternative MR-based morphometric approach is that of cortical thickness analysis (Kim et al., 2005). Cortical thickness methods have been shown to be more sensitive in detecting alterations in cortical morphology than the former volumetric approach (Eskildsen et al., 2009, Hutton et al., 2009), and have been proven to be reliable, in terms of spatial localization and magnitude of absolute cortical thickness measurement (Dickerson et al., 2008). Moreover, cortical volumetric approaches typically require an a priori definition of a small number of regions-of-interest (ROIs), limiting the possibility of exploratory analyses of cortical regions, whereas surface representations allow a landmark-based assignment of cortical regions to the entire cortex. Because the networks involved in gait are scattered throughout the entire brain in healthy individuals (la Fougere et al., 2010), a more comprehensive and data-driven analysis, such as is provided by this latter approach, is desirable.

It is furthermore not clear whether and to what extent this relationship is (in)dependent of the co-existing WMLs and lacunar infarcts. It could be hypothesized that cortical atrophy in subjects with SVD, and subsequently gait disturbances, may partly be due to WMLs and lacunar infarcts. These lesions may cause disruption of axons traversing the white matter with secondary neuronal degeneration of networks connecting relevant cortical regions, involved in the control of gait. Rosano et al. found that WMLs and lacunar infarcts did not substantially change the regression coefficients of these associations, but they assessed WMLs only semi-quantitatively (Rosano et al., 2007, Rosano et al., 2008).

Using surface-based cortical thickness analysis, we aimed to identify the association between regional cortical thickness and several spatiotemporal gait parameters in a large group of elderly individuals with cerebral SVD. A secondary objective of this study was to examine whether these associations were dependent on SVD, including WMLs and lacunar infarcts.