Abstract
The diagnosis of Parkinson's disease (PD) is currently anchored on clinical motor symptoms, which appear more than 20 years after initiation of the neurotoxicity. Extra-nigral involvement in the onset of PD with probable nonmotor manifestations before the development of motor signs, lead us to the preclinical (asymptomatic) or prodromal stages of the disease (various nonmotor or subtle motor signs). REM sleep behavior disorder (RBD) and depression are established prodromal clinical markers of PD and predict worse motor and cognitive outcomes. Nevertheless, taken by themselves, these markers are not yet claimed to be practical in identifying high-risk individuals. Combining promising markers may be helpful in a reliable diagnosis of early PD. Therefore, we aimed to detect neural correlates of RBD and depression in 93 treatment-naïve and non-demented early PD by means of diffusion MRI connectometry. Comparing four groups of PD patients with or without comorbid RBD and/or depressive symptoms with each other and with 31 healthy controls, we found that these two non-motor symptoms are associated with lower connectivity in several white matter tracts including the cerebellar peduncles, corpus callosum and long association fibers such as cingulum, fornix, and inferior longitudinal fasciculus. For the first time, we were able to detect the involvement of short association fibers (U-fibers) in PD neurodegenerative process. Longitudinal studies on larger sample groups are needed to further investigate the reported associations.
Highlights
Parkinson’s disease (PD), a form of α-synucleinopathy neurodegeneration [1], is manifested by a heterogeneous combination of motor and non-motor symptoms (NMS) [2]
There are few discrepancies between PD patients enrolled in this study and those investigated in our two previous studies, as we attempted to include patients matched in their demographic, motor and other non-motor symptoms other than depression and Rapid Eye movement (REM) sleep behavior disorder (RBD) in the present study
healthy controls (HC) were matched with PD patients regarding age, sex, handedness, education years, Montreal Cognitive Assessment (MoCA), and Epworth Sleepiness Scale (ESS) scores, while performed better than PD patients on Geriatric Depression Scale (GDS), RBD, and University of Pennsylvania Smell Identification Test (UPSIT)
Summary
Parkinson’s disease (PD), a form of α-synucleinopathy neurodegeneration [1], is manifested by a heterogeneous combination of motor and non-motor symptoms (NMS) [2]. The golden time to halt the disease progression is missed. Rapid Eye movement (REM) sleep behavior disorder (RBD), characterized by unpleasant dreams and loss of normal muscle atonia [4], has by far proved to be the strongest precursor of upcoming PD [3] and with more than 75% conversion rate, is considered as an evolving synucleinopathy [5,6,7]. With an estimated prevalence of 15–60% in PD patients [8], baseline RBD is attributed to more aggressive clinical subtype with worse motor and non-motor symptoms, especially depressive disorders and cognitive decline [9]. Combining RBD with another prodromal symptom may solve this task by increasing the risk of conversion [10]
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