Abstract
BackgroundEven though Parkinson's disease (PD) is typically viewed as largely affecting gray matter, there is growing evidence that there are also structural changes in the white matter. Traditional connectomics methods that study PD may not be specific to underlying microstructural changes, such as myelin loss.ObjectiveThe primary objective of this study is to investigate the PD‐induced changes in myelin content in the connections emerging from the basal ganglia and the brainstem. For the weighting of the connectome, we used the longitudinal relaxation rate as a biologically grounded myelin‐sensitive metric.MethodsWe computed the myelin‐weighted connectome in 35 healthy control subjects and 81 patients with PD. We used partial least squares to highlight the differences between patients with PD and healthy control subjects. Then, a ring analysis was performed on selected brainstem and subcortical regions to evaluate each node's potential role as an epicenter for disease propagation. Then, we used behavioral partial least squares to relate the myelin alterations with clinical scores.ResultsMost connections (~80%) emerging from the basal ganglia showed a reduced myelin content. The connections emerging from potential epicentral nodes (substantia nigra, nucleus basalis of Meynert, amygdala, hippocampus, and midbrain) showed significant decrease in the longitudinal relaxation rate (P < 0.05). This effect was not seen for the medulla and the pons.ConclusionsThe myelin‐weighted connectome was able to identify alteration of the myelin content in PD in basal ganglia connections. This could provide a different view on the importance of myelination in neurodegeneration and disease progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Highlights
Parkinson’s disease (PD) is a neurodegenerative disorder that is characterized by motor and nonmotor symptoms
The mean-centered partial least squares (PLS) analysis showed that most of the connections that demonstrated a difference between healthy control subjects (HCs) and PD patients emerged from the basal ganglia (Fig. 2)
We have shown that the myelinweighted connectome was able to identify alterations of the myelin content along connections that were mostly emerging from the basal ganglia
Summary
Parkinson’s disease (PD) is a neurodegenerative disorder that is characterized by motor and nonmotor symptoms. PD is considered to be a disease that mainly affects the gray matter, the dopaminergic neurons that affect motor function This disease has been characterized by the accumulation of misfolded ɑ-synuclein proteins across the brain.[1,2,3,4] It has been noted that the myelination status and the size of the axons could play an important role in neurodegeneration in PD.[5]. An alternative hypothesis for the disease spreading has been proposed, according to which the disease first starts in the cortex and spreads to the rest of the brain.[7,8] It has been recently suggested that neurodegeneration in patients with PD with rapid eye movement sleep behavior disorder (RBD; PDRBD) follows the Braak model (“bottom-up”) of disease progression,[9,10] whereas neurodegeneration in patients with PD without RBD (PDnonRBD) follows the alternative “top-down” model (from cortex to brainstem).[10,11]
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