Loss of white matter integrity is associated with gait disorders in cerebral small vessel disease

Abstract

Gait disturbances are common in the elderly. Cerebral small vessel disease, including white matter lesions and lacunars infarcts, is thought to disrupt white matter tracts that connect important motor regions, hence resulting in gait disturbances. Pathological studies have demonstrated abnormalities in white matter that may appear normal on brain imaging. The loss of integrity in such normal-appearing white matter may partly be due to small vessel disease and may play a role in causing gait disturbances. The white matter regions involved in these gait disturbances, both in white matter lesions and normal-appearing white matter, remain unclear. We, therefore, aimed to investigate the relation between the location of white matter lesions and gait using voxel-based morphometry analysis, as well as between white matter integrity and gait by applying tract-based spatial statistics to diffusion tensor imaging parameters. Magnetic resonance imaging was carried out on 429 individuals in the age range of 50 and 85 years, with cerebral small vessel disease without dementia or parkinsonism. Gait was assessed quantitatively. White matter lesions, especially in the centrum semiovale and periventricular frontal lobe, were related to a lower gait velocity, shorter stride length and broader stride width. Loss of white matter integrity, as indicated by a lower fractional anisotropy and higher mean diffusivity, in numerous regions was related to a lower gait performance. Most of these regions were located in the normal-appearing white matter. The strongest significant association was found in the corpus callosum, particularly the genu. Most of the associations in the normal-appearing white matter disappeared after controlling for white matter lesions and lacunar infarcts, except for some in the corpus callosum. In conclusion, our study showed that using a combination of voxel-based morphometry analysis of the white matter lesions and diffusion tensor imaging is of added value in investigating the pathophysiology of gait disturbances in subjects with small vessel disease. Our data demonstrate that, in elderly subjects with small vessel disease, widespread disruption of white matter integrity, predominantly in the normal-appearing white matter, is involved in gait disturbances. In particular, loss of fibres interconnecting bilateral cortical regions, especially the prefrontal cortex that is involved in cognitive control on motor performance, may be important. The most important mechanisms underlying affected normal-appearing white matter are probably a direct effect of small vessel disease or, indirectly, remote effects of white matter lesions and lacunar infarcts.

White Matter Microstructural Damage on Diffusion Tensor Imaging in Cerebral Small Vessel Disease

“…Analyses for each cognitive domain showed the strongest relationship between (1) cingulum bundle microstructural integrity and verbal memory performance and (2) frontal WM and psychomotor speed. 8 However, in the same cohort, the main predictors for the development of incident dementia at 5 years were WM and hippocampal volumes, 34 whereas baseline WM integrity was not associated with decline in cognitive performances 35 In the Vascular Mild Cognitive Impairment Tuscany study, WM microstructural damage was more strongly reflected in Montreal cognitive assessment than mini mental status examination performances, 36 possibly for the presence in Montreal cognitive assessment of items reflecting executive functions and psychomotor speed.…”

Diffuse Tract Damage in the Hemispheric Deep White Matter May Correlate with Global Cognitive Impairment and Callosal Atrophy in Patients with Extensive Leukoaraiosis

“…24 The usefulness of TBSS for voxel-based analyses of DTI maps has been reported in patients with leukoaraiosis and other disease processes involving white matter. 14,24 First, any patient's FA image was aligned to every other patient's FA image, and the most representative image among all patients' FA images was identified and selected as the target image. Next, this target image was affine-aligned into a 1 ϫ 1 ϫ 1 mm 3 MNI 152 space.…”

“…Histogram and voxel-based analyses of these maps are useful in evaluating white matter tract damage in patients with extensive WMLs. [12][13][14] The purpose of this study was to investigate whether HDWM tract damage is associated with global cognitive impairment and callosal atrophy in patients with extensive WMLs and lacunar infarcts, by using histogram and voxel-based analyses of DTI maps.…”

Lower Magnetization Transfer Ratio in the Forceps Minor Is Associated with Poorer Gait Velocity in Older Adults

“…14,19,24 The only MTR study in healthy, older adults described a relationship between wholebrain MTR and gait velocity. 23 The authors of this investigation quantified MTR changes globally by using histogram-based metrics.…”

“…We hypothesized that alterations, if any, would mainly be located within the frontal white matter because intact fontal subcortical pathways have been reported to be crucial for maintenance of gait performance at a higher level. 6,24 …”