Objective: To determine if microstructural changes in the normal appearing white matter of PD are associated with clinical manifestations of disease.

Background: White matter (WM) is typically considered unaffected in PD, a neurodegenerative disease characterized by motor dysfunction and neuropsychiatric symptoms. Recent evidence utilizing Diffusion Tensor Imaging suggests WM microstructural alterations over the course of the disease, but newer magnetic resonance sequences, such as Myelin Water Fraction (MWF) provide a more specific measure of myelin. Here, we used a multivariate approach to investigate the association between MWF and clinical measures such as global motor, tremor, and neuropsychiatric scores in PD patients.

Methods: Thirty-three idiopathic PD subjects (13 with apathy, 20 without apathy) were scanned and clinically assessed at the movement disorders clinic (University of British Columbia). Twenty WM regions of interest (ROIs) were considered as MWF features and 6 clinical scores were combined in a partial least squares (PLS) analysis to find a relation between the two multivariate sets. A Leave-One-Out Cross Validation approach was used to determine which WM ROIs had the greatest influence on the correlation.

Results: Three significant PLS components were identified. The first PLS component represented a significant association between MWF features in the left/ right cingulum hippocampus, splenium, left superior longitudinal fasciculus, and left/ right arcuate and UPDRS-3 motor scores (R: -0.66, p: 0.0001). The second component linked MWF features in the left/ right corticospinal tracts, left cingulum hippocampus, left/ right superior longitudinal fasciculi, and right thalamic radiation with postural and kinetic tremor scores (R: -0.38, p: 0.0431). The third PLS component linked MWF in the left/ right thalamic radiation, left cingulum hippocampus, splenium, and left/ right arcuate to clinical features of depression (R: -0.50, p: 0.007), apathy (R: -0.55, p: 0.002), and fatigue (R: -0.51, p: 0.005).

Conclusions: A myriad of clinical manifestations of PD are associated with changes in WM myelination, even in normal-appearing WM tracts in PD, possibly as a result of recently described neuron-to-oligodendrocyte transfer of α-synuclein. Further exploration of MWF may demonstrate its potential as a complimentary imaging marker in describing the progression of PD.

References: Reyes, J. F., Rey, N. L., Bousset, L., Melki, R., Brundin, P. and Angot, E. (2014), Alpha-synuclein transfers from neurons to oligodendrocytes. Glia, 62: 387–398. doi:10.1002/glia.22611.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/microstructural-changes-in-normal-appearing-white-matter-in-parkinsons-disease-pd-correlate-with-motor-tremor-and-neuropsychiatric-scores/