To examine the associations between neuroimaging and gait and balance abnormalities in progressive supranuclear palsy (PSP).

PSP is a neurodegenerative disorder characterized primarily by tau inclusions and neurodegeneration in the midbrain, basal ganglia, thalamus, premotor and frontal cortex. While PSP can present with a variety of clinical syndromes, gait impairments and postural instability are common early features.

MRI atrophy, white matter tracts degeneration from diffusion tensor imaging, flortaucipir-PET uptake as well as laboratory-based gait and balance measurements were assessed in 19 PSP patients. Associations between these quantities were assessed with univariate and multivariate analyses.

Principal component analysis on gait variables identified velocity, stride length, length of gait phases and dynamic stability as the main contributors to the first component, which was associated with disruption of the posterior thalamic radiation, external capsule, superior cerebellar peduncle, superior fronto-occipital fasciculus, corpus callosum and sagittal stratum, atrophy in frontal and precentral regions and flortaucipir-PET uptake in the precentral gyrus. The main contributor to the second principal component was cadence, which was unexpectedly higher in patients presenting higher mean diffusivity, suggesting compensatory gait strategies in PSP. Postural imbalance was the main contributor to the third principal component, which was mainly related to flortaucipir-PET uptake in the left paracentral lobule and supplementary motor area and disruption of various white matter tracts. Spearman’s correlations on gait and imaging quantities revealed differences between the PSP Richardson’s syndrome sub-group (n=13) and the other PSP variants. A partial least square model identified flortaucipir-PET uptake in midbrain, basal ganglia and thalamus as the main correlate of speed and dynamic component of gait in PSP.

Although causality cannot be established, our study sheds light on neurodegeneration of brain regions and white matter tracts that underlies gait and balance impairment in PSP, suggesting that there might be variation across PSP variants.