White matter integrity is associated with gait impairment and falls in mild cognitive impairment. Results from the gait and brain study

Abstract

Background: Mild Cognitive Impairment (MCI) is an intermediate state between normal cognition and dementia that is associated with twice the risk of falls. It is unknown whether white matter integrity (WMI) is associated with increased risk of falls in MCI. The purpose of this study was to evaluate if early changes in WMI were associated with gait impairment and falls.

Methods: Forty-three participants with MCI from the Gait and Brain Study underwent standardized assessment of cognition, gait performance under single and dual-task conditions (walking while talking), and WMI using 3 Tesla diffusion tensor imaging (DTI). Macro-structural imaging characteristics (white and grey matter morphology) as well as microstructural WMI parameters were examined for associations with falls and gait performance. Significantly associated WM tracts were then used to test the interplay between WMI and history of falls, after adjusting for other important covariates.

Results: Multiple WM tracts (corpus callosum, forceps minor, and the left inferior fronto-occipital fasciculus) were significantly associated with history of falls and lower dual-task gait performance. A multivariable regression model showed that fall history was associated with the radial diffusivity in the forceps minor, even after adjusting for education, sex, BMI, MMSE scores, comorbidities, gait velocity and WMH volume as covariates.

Conclusions: Multiple WM tracts that are known to be involved in executive and visuospatial functions were preferentially affected in MCI individuals with history of falls. Our preliminary findings support the notion that WMI in key brain regions may increase risk of falls in older adults with MCI.

Keywords: Diffusion tensor imaging; Executive function; Falls; Gait; MCI; Microstructure; White matter.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Fig. 1

WM fiber tract ROIs used for region specific analysis. Fiber tract probability maps were thresholded at 10% and converted to masks to be used for region-specific analysis of TBSS produced collapsed diffusion parameters. The ROIs are shown in the sagittal (Sag), coronal (Cor) and axial (Ax) direction superimposed on a 152 MNI 1 mm brain template 3D surface render. The tracts are: Superior Longitudinal Fasciculus - Blue, Inferior longitudinal Fasciculus - Yellow, IFOF - Inferior Fronto-Occipital Fasciculus - Brown, Corpus Callosum – not shown, Forceps Minor - Purple, Forceps Major - Green, CS Corticospinal tract - Red, Anterior Thalamic Radiation - Teal, Uncinate Fasciculus – Pink.

Fig. 2

WMH Probability map in MCI. The probability distribution of WMHs are shown in red-yellow superimposed on the 1 mm resolution MNI T1 template. The color bar denotes the percentage of subjects who had WMHs in each image voxel. WMH near the ventricles are common in MCI patients, with less frequent presentation away from the ventricles and toward the brain periphery. The arrow head points at a location distant from the ventricles with a moderate frequency of WMHs among the cohort studied.

Fig. 3

Significantly lower WMI clusters (Pink) in patients with history of falling compared to those without (Fallers WMI is compromised compared to non-fallers WMI) shown on the left. Significant correlations between the number of falls reported in the one year time frame prior to the imaging session and different scalar DTI parameters (red-yellow: negative correlation, blue-light blue: positive correlation) shown on the right. All voxel-wise results were acquired by nonparametric permutation inference testing controlling for age, sex, years of education, BMI and MMSE scores. Data is presented overlaid on the MNI 152 1 mm space standard brain, and average skeletonized WM tracts in green.

Fig. 4

Significantly correlated WM clusters with gait velocity. Significant correlations (p ≤ .0125) between gait velocity and WMI as measured by different scalar DTI parameters (only correlations between reduced WMI and reduced gait performance, ie velocity, are shown). The different gait tests are color coded: yellow: single-task; green: dual-task counting; blue: dual-task naming animals; red: dual-task serial 7's. All voxel-wise results were acquired by nonparametric permutation inference testing controlling for age, sex, years of education, BMI and MMSE scores. Data is presented overlaid FMRIB58 1 mm space standard brain.

Fig. 5

Circular plot of all WM tracts containing voxels clusters significantly correlated with gait velocity (single- or dual-tasks) as well as associated with reduced integrity in fallers compared with non-fallers. All voxel-wise results were acquired by nonparametric permutation inference testing controlling for age, sex, years of education, BMI and MMSE scores. Colors correspond to DTI parameters and comparisons made in Fig. 2, Fig. 3. Significant correlations are distinguished for left (vertical lines), right (horizontal lines), and bilateral tracts accordingly.