Objective: The objective of this study was to determine if the novel diffusion metric, free water (FW), from two-tensor modeling could sensitively identify microstructural alterations in white matter in PD-related cognitive decline.

Background: Cognitive impairment in Parkinson’s disease (PD) has been associated with WM alterations. We hypothesized that various biological/pathological processes may converge to alter microstructure in the corpus callosum (CC), the major connection between the hemispheres. To test this hypothesis, we investigated whether diffusion tensor imaging (DTI) metrics, particularly FW could gauge and/or predict cognitive decline during PD progression.

Method: Baseline DTI and whole brain tractography (using a two-tensor approach) were obtained from 87 Control and 110 PD subjects. Fibers passing through the CC were isolated from the full CC as well as genu, body, and splenium of the CC. The following DTI metrics in CC and CC subregions were obtained: FW, FW-corrected fractional anisotropy (FA), mean diffusion (MD) and axial diffusivity (AD), and radial diffusivity (RD). These baseline DTI metrics were associated with baseline and 3y change in Montreal Cognitive Assessment (MoCA) scores.

Results: At baseline, no diffusion metric was different between Control and PD subjects in CC. Within PD subjects, CC FW correlated with MoCA score (r=-0.320, p=0.002). There is, however, no significant association between CC FW and MoCA score (r=-0.045, p= 0.685) in control subjects. Longitudinally, baseline FW (r=-0.229, p<0.047) in the CC correlated with 3y change in MoCA in PD subjects that finished the study. There were no significant associations found among other free water-corrected DTI metrics both at baseline and longitudinally.

Conclusion: Microstructural properties in the CC, detected by FW, may mark cognitive status and future decline in PD. [Abstract also presented at 2020 AAT-AD/PD on April 2 2020]

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MDS Abstracts - https://www.mdsabstracts.org/abstract/free-water-in-corpus-callosum-is-sensitive-to-parkinsons-disease-related-cognitive-decline/