Objective: To identify white matter (WM) alterations associated with cognitive impairment in progressive supranuclear palsy (PSP).

Background: PSP is accompanied with cognitive impairment [1;2], but consensus is lacking regarding the extent to which WM atrophy patterns contribute to underlying pathologies [3].

Method: 15 PSP patients (5 male; age: 70.1±7.0 years; disease duration: 14±14 months) completed the Montreal Cognitive Assessment (MoCA). Multi-shell diffusion MRI (dMRI) was acquired on a 3T Siemens Prisma according to the Lifespan Human Connectome Project in Aging and preprocessed according to its minimal preprocessing pipeline [4]. dMRI parameters, i.e. fractional anisotropy (FA) and mean diffusivity (MD), were computed using dtifit in FSL v.6.0.2 and further processed with tract-based spatial statistics (TBSS). Voxel-wise analyses were applied for correlations with MoCA score using general linear models and permutation testing (n=500), controlling for multiple comparisons and applying Threshold-Free Cluster Enhancement (TFCE; p≤0.05, FWE-corrected).

Results: FA values exhibited significant positive correlations with MoCA scores (M=19.62±4.50) in the following WM tracts: bilateral middle cerebellar peduncle; external capsule; bilateral optic radiation; bilateral superior longitudinal fasciculus; bilateral anterior corona radiata; bilateral inferior fronto-occipital fasciculus; left posterior corona radiata; right cingulum. Complementing this, we found significant negative correlations between MD and MoCA scores in: bilateral anterior thalamic radiation; bilateral corticospinal tract; corpus callosum (genu;body;splenium); bilateral inferior fronto-occipital fasciculus; bilateral superior longitudinal fasciculus, bilateral middle cerebellar peduncle (Fig.1).

Conclusion: This study identified widespread patterns of WM alterations associated with cognitive impairment; especially FA decrease in the superior longitudinal fasciculus can be linked to cognitive decline through fronto-parietal decoupling. MD increase was more widespread, extending onto commissural fibres and subcortical regions, which project to motor and somatosensory areas. These findings complement known PSP-specific grey matter degeneration in regions that play an important role in clinical dysfunction. This underlines that whole-brain atrophy networks need to be considered to gain a better understanding of the complex symptom-characteristics of PSP [5-8].

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MDS Abstracts - https://www.mdsabstracts.org/abstract/increased-md-and-decreased-fa-reflect-cognitive-impairment-in-psp/