Microstructural Changes in Patients With Parkinson's Disease Comorbid With REM Sleep Behaviour Disorder and Depressive Symptoms

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.

Assessing White Matter Pathology in Early-Stage Parkinson Disease Using Diffusion MRI: A Systematic Review

“…Ghazi Sherbaf et al (69) published several studies by using this technique utilizing PPMI database. They studied PD subjects with depression and sleep behavior disorder (70)(71)(72). Additionally, they found that PD patients exhibited negative correlations between QA and insulinlike growth factor 1 level in several WM locations, including the middle cerebellar peduncle, left and right cingulum, and genu and splenium of the corpus callosum (72); additionally, they demonstrated that the blood marker apolipoprotein A-1 can predict microstructural changes in WM regions in early-stage PD patients with undisturbed cognition and mild motor disability (68).…”

“…They studied PD subjects with depression and sleep behavior disorder (70)(71)(72). Additionally, they found that PD patients exhibited negative correlations between QA and insulinlike growth factor 1 level in several WM locations, including the middle cerebellar peduncle, left and right cingulum, and genu and splenium of the corpus callosum (72); additionally, they demonstrated that the blood marker apolipoprotein A-1 can predict microstructural changes in WM regions in early-stage PD patients with undisturbed cognition and mild motor disability (68). Utilizing QA in a connectome analyses, Haghshomar et al (74) previously studied the structural correlation of various WM tracts in 81 early-stage PD patients with the whole-blood neutrophil-to-lymphocyte ratio and identified that the QA index correlated with this ratio in the bilateral cingulum, body and left crus of fornix, bilateral corticospinal tract, body and splenium of corpus callosum, and superior cerebellar peduncle.…”

Changes in Day/Night Activity in the 6-OHDA-Induced Experimental Model of Parkinson’s Disease: Exploring Prodromal Biomarkers

“…Remarkably, slight motor symptoms (<40–60% of dopaminergic neuronal cell loss) have been also associated to the prodromal stage when they do not meet the criteria for the clinical diagnosis of PD ( Mahlknecht et al, 2015 ). Thus, it is essential to establish a correlation between the early manifestations of PD (prodromal stage) with the clinical and pathological stage for an early diagnosis of PD ( Mahlknecht et al, 2015 ; Liepelt-Scarfone et al, 2017 ; Sherbaf et al, 2018 ).…”

Parkinson’s Disease-Induced Zebrafish Models: Focussing on Oxidative Stress Implications and Sleep Processes

“…Another PD-occurring sleep disturbance is rapid eye movement sleep behaviour disorder characterized by motor behaviours and different vocalizations [135,136]. By comparison with the other sleep disturbance symptoms in PD, rapid eye movement sleep behaviour disorder is being considered a premotor symptom, and in some cases a disease development marker [137] due to the fact that 40 to 65% of those diagnosed with rapid eye movement sleep behaviour disorder are further later diagnosed with PD [137][138][139][140]. Excessive daytime sleepiness (EDS) and fatigue are also present in PD [129,131,141,142].…”