Parkinson’s Disease

Parkinson’s disease (PD) is the second most common neurodegenerative disease, with significant socioeconomic burdens. One of the crucial pathological features of PD is the loss of dopaminergic neurons in the substantia nigra (SN). However, the exact pathogenesis remains unknown. Moreover, therapies to prevent neurodegenerative progress are still being explored. We performed bioinformatics analysis to identify candidate genes and molecular pathogenesis in the SN of patients with PD. We analyzed the expression profiles, GSE49036 and GSE7621, which included 31 SN tissues in SN tissues in healthy control samples, and identified 86 common differentially expressed genes (DEGs). Then, GO and KEGG pathway analyses of the identified DEGs were performed to understand the biological processes and significant pathways of PD. Subsequently, a protein-protein interaction network was established, with 15 hub genes and four key modules which were screened in this network. The expression profiles, GSE8397 and GSE42966, were used to verify these hub genes. We demonstrated a decrease in the expression levels of 14 hub genes in the SN tissues of PD samples. Our results indicated that, among the 14 hub genes, DRD2, SLC18A2, and SLC6A3 may participate in the pathogenesis of PD by influencing the function of the dopaminergic synapse. CACNA1E, KCNJ6, and KCNB1 may affect the function of the dopaminergic synapse by regulating ion transmembrane transport. Moreover, we identified eight microRNAs (miRNAs) that can regulate the hub genes and 339 transcription factors (TFs) targeting these hub genes and miRNAs. Subsequently, we established an mTF-miRNA-gene-gTF regulatory network. Together, the identification of DEGs, hub genes, miRNAs, and TFs could provide better insights into the pathogenesis of PD and contribute to the diagnosis and therapies.

Introduction. Drooling in Parkinson’s disease (PD) is frequent but often goes underrecognized. Our aim was to examine the prevalence of drooling in a PD cohort and compare it with a control group. Specifically, we identified factors associated with drooling and conducted subanalyses in a subgroup of very early PD patients. Patients and Methods. PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30-day follow-up (V2) from 35 centers in Spain from the COPPADIS cohort were included in this longitudinal prospective study. Subjects were classified as with or without drooling according to item 19 of the NMSS (Nonmotor Symptoms Scale) at V0, V1 (1-year ± 15 days), and V2 for patients and at V0 and V2 for controls. Results. The frequency of drooling in PD patients was 40.1% (277/691) at V0 (2.4% (5/201) in controls;  < 0.0001), 43.7% (264/604) at V1, and 48.2% (242/502) at V2 (3.2% (4/124) in controls;  < 0.0001), with a period prevalence of 63.6% (306/481). Being older (OR = 1.032;  = 0.012), being male (OR = 2.333;  < 0.0001), having greater nonmotor symptom (NMS) burden at the baseline (NMSS total score at V0; OR = 1.020;  < 0.0001), and having a greater increase in the NMS burden from V0 to V2 (change in the NMSS total score from V0 to V2; OR = 1.012;  < 0.0001) were identified as independent predictors of drooling after the 2-year follow-up. Similar results were observed in the group of patients with ≤2 years since symptom onset, with a cumulative prevalence of 64.6% and a higher score on the UPDRS-III at V0 (OR = 1.121;  = 0.007) as a predictor of drooling at V2. Conclusion. Drooling is frequent in PD patients even at the initial onset of the disease and is associated with a greater motor severity and NMS burden.

This pilot study aimed to explore how caregiver spouses make sense of themselves one and five years after their partner’s deep brain stimulation (DBS) surgery for Parkinson’s disease. 16 spouse (8 husbands and 8 wives) caregivers were recruited for the interview. Eight struggled to reflect on their own lived experience and primarily focused on the impact of PD on their partners, such that their transcripts were no longer viable for interpretative phenomenological analysis (IPA). A content analysis showed (1) how these 8 caregivers shared less than half as many self-reflections than the other caregivers, (2) that there was a bias to reflect on their partner’s experience answering the opening question, (3) the bias continued when answering subsequent questions, and (4) there was a lack of awareness of this bias. No other patterns of behaviour or themes were able to be extracted. The remaining 8 interviews were transcribed and analysed using IPA. This analysis discovered 3 inter-related themes: (1) DBS allows carers to question and shift the caregiver role, (2) Parkinson’s unites and DBS divides, and (3) seeing myself and my needs, DBS enhances visibility. How these caregivers interacted with these themes depended on when their partners were operated. The results suggested that spouses maintained the role of caregiver one year post DBS because they struggle to identify themselves in any other way but were more comfortable reassociating into the role of spouse 5 years post surgery. Further inquiry into caregiver and patient identity roles post DBS is recommended as a means of supporting their psychosocial adjustment after surgery.

This study aimed to explore morphological changes of hippocampal subfields in patients with multiple system atrophy (MSA) with and without cognitive impairment using FreeSurfer-automated segmentation of hippocampal subfield techniques and their relationship with cognitive function. We enrolled 75 patients with MSA classified as cognitively impaired MSA (MSA-CI, n = 40) and cognitively preserved MSA (MSA-CP, n = 35), as well as 68 healthy controls. All participants underwent three-dimensional volume T1-weighted magnetic resonance imaging. The hippocampal subfield volume was measured using FreeSurfer version 7.2 and compared among groups. Regression analyses were performed between the hippocampal subfield volumes and cognitive variables. Compared with healthy controls, the volume of the right cornu ammonis (CA) 2/3 was significantly lower in the MSA-CI group () and that of the left fimbria was significantly higher in the MSA-CP group (). Results of linear regression analysis showed that the right CA2/3 volume was significantly correlated with the Frontal Assessment Battery score in patients with MSA (adjusted R² = 0.282, β = 0.227, and ). The hippocampal subfield volume decreased in patients with MSA-CI, even at the early disease stages. Specific structural changes in the hippocampus might be associated with cognitive deficits in MSA.

Background. In Parkinson’s disease (PD), dopamine deficiency is present not only in the nigrostriatal pathway but also in the retinal and visual pathways. Optic coherence tomography (OCT) can be used as morphological evidence of visual influence from early nonmotor symptoms. The aim of this study was to investigate the relationship of OCT and visual evoked potentials (VEPs) of eyes with the severity of clinical findings and ocular findings in PD. Methods. A group of 42 patients diagnosed with idiopathic PD and a control group of 29 people between the ages of 45–85 were included in our study. VEP was recorded in the patient and control groups. OCT measurement was made with the Optovue spectral-domain device. Foveal thickness and macular volume were measured in the foveal region and in the parafoveal and perifoveal regions in the temporal, superior, nasal, and inferior quadrants. RNFL (retinal nerve fiber layer) was measured in temporal, superior, nasal, and inferior quadrants. Ganglion cell complex (GCC) was evaluated in the superior and inferior quadrants. Using the UPDRS clinical scale, the relationship between measurements and the differences between the control group and the patient group were evaluated. Results. Among the OCT values in our study, foveal, parafoveal, perifoveal thickness, macular volume, RNFL, and GCC measurements were performed for the right and left eyes, and no difference was found between the patient group and the control group. There was no difference in VEP amplitude and latency values between the patient and control groups. The relationships between UPDRS and modified Hoehn Yahr staging and OCT and VEP measurements in the patient revealed no correlation. Conclusions. Studies on whether OCT measurements can functionally be a marker or which segments are more valuable for disease progression in patients with PD are needed. Visual dysfunction in PD cannot be attributed only to retinal pathology; however, the retina may provide monitoring of the status of dopaminergic neurodegeneration and axonal loss in PD.

Introduction. Fatigue and orthostatic hypotension (OH) are common and disabling nonmotor symptoms (NMSs) of Parkinson’s disease (PD), but none of the studies have reported on the longitudinal association between fatigue and OH. Methods. Drug-naïve PD patients were recruited from a hospital-based cohort and evaluated with the Parkinson Fatigue Scale (PFS), head-up tilt test, Unified PD Rating Scale, Hoehn and Yahr stage, Montreal Cognitive Assessment, Scale for Outcomes in PD-Autonomic (SCOPA-AUT), Beck Depression Inventory (BDI), Beck Anxiety Inventory, PD Sleep Scale, and medications at the baseline and follow-up visits. Results. A total of 80 patients were included, and the mean ages were 66.6 and 63.8 years in the fatigue and nonfatigue groups, respectively. The prevalence of fatigue was 17.5% (14/80) at the baseline and follow-up (mean follow-up: 23.3 ± 9.9 months). The prevalence of OH in the fatigue group was 57.1%, and it was significantly higher than that of the nonfatigue group. Six of the 14 patients (42.9%) in the fatigue group had persistent fatigue at the follow-up, and eight of them (57.1%) converted to the nonfatigue group. Logistic regression analysis demonstrated that the changes of BDI and the presence of OH at the baseline were the predictors for fatigue in drug-naïve PD. Conclusion. Fatigue is a common NMS in PD but can vary depending on the disease course. OH and depression are the most relevant predictors for the development of fatigue in drug-naïve PD. The present study suggests that the management of autonomic symptoms and depression might be helpful for managing fatigue in PD.