Associations between white and grey matter damage and gait impairment in cerebral amyloid angiopathy

Cerebral amyloid angiopathy (CAA) is associated with white matter damage and neurodegeneration. Gait is impaired in CAA; however, the neural basis of this impairment is unclear.

Are gait impairments in patients with CAA associated with altered cerebral white matter diffusivity and/or atrophy of cortical and subcortical grey matter.

Participants with CAA (n=29), Alzheimer's disease (AD; n=16), and normal controls (n=47) were included. Gait was assessed using a 6 m walkway with parameters categorized into rhythm, pace, postural control, and variability domains. The dual-task cost (DTC) of gait speed was calculated for counting backwards, animal fluency, and serial sevens tasks. Whole-brain white matter disruption was quantified using the peak width of skeletonized mean diffusivity (PSMD), and thickness and volume of select cortical, subcortical, and cerebellar regions were quantified using FreeSurfer.

In CAA participants, associations were found between PSMD and pace (standardized parameter estimate (β), 95 % confidence interval (CI): 0.17, 0.03-0.32), and medial orbital frontal cortical thickness and counting backwards DTC (parameter estimate (PE), 95 % CI: -5.7 %/SD, -0.24 to -11.23). Across all groups, including CAA, associations were found between PSMD and pace, variability, counting backwards DTC, and animal fluency DTC; between frontal cortical thickness and pace, counting backwards DTC, and animal fluency DTC; between cortical regions affected by AD (inferior parietal cortex, inferior and middle temporal gyrus) and counting backwards DTC; and between thalamus volume and postural control.

Reduced white matter structural integrity and grey matter loss is associated with poor overall gait performance in CAA, AD, and normal controls.