Parkinson's Disease最新文献

The study aimed to investigate the neural changes that differentiate Parkinson's disease patients with freezing of gait and age-matched controls, using ambulatory electroencephalography event-related features. Compared to controls, definite freezers exhibited significantly less alpha desynchronization at the motor cortex about 300 ms before and after the start of overground walking and decreased low-beta desynchronization about 300 ms before and about 300 and 700 ms after walking onset. The late slope of motor potentials also differed in the sensory and motor areas between groups of controls, definite, and probable freezers. This difference was found both in preparation and during the execution of normal walking. The average frontal peak of motor potential was also found to be largely reduced in the definite freezers compared with the probable freezers and controls. These findings provide valuable insights into the underlying structures that are affected in patients with freezing of gait, which could be used to tailor drug development and personalize drug care for disease subtypes. In addition, the study's findings can help in the evaluation and validation of nonpharmacological therapies for patients with Parkinson's disease.

Background: Postural instability has been identified as a fall risk factor with a significant impact on the quality of life of patients with Parkinson's disease (PD). The aim of this study was to compare the center of pressure (COP) between faller and nonfaller patients with PD during static standing.

Methods: Thirty-two faller patients and 32 nonfaller patients with PD participated in this study. All patients performed the static balance test on a force plate. COP data were recorded during quiet standing. Mean distance, sway area, mean velocity, mean frequency, and peak power were derived from the COP data. Statistical analysis was performed using independent t-tests to compare faller and nonfaller patients.

Results: Fallers presented a greater average distance, wider sway area, faster average speed, and greater peak power than nonfallers (p < 0.05). In contrast, no significant group differences were observed in peak frequency and mean frequency (p > 0.05).

Conclusions: Although falls occur during dynamic activities, our study demonstrated that even a safe and simple static postural balance test could significantly differentiate between faller and nonfaller patients. Thus, these results suggest that quantitatively assessed static postural sway variables would be useful for distinguishing prospective fallers among PD patients.

Objective: We aimed to assess the validity and reliability of the Persian version of the NonMotor Symptoms Scale (NMSS) in Iranian patients with PD.

Methods: This cross-sectional study was conducted in patients with PD. After the cross-cultural adaptation of the NMSS, the acceptability, reliability, precision, and validity of the Persian NMSS were evaluated. For this purpose, in addition to NMSS, we used the following measures: Scales for Outcomes in Parkinson's Disease (SCOPA)-Autonomic (SCOPA-AUT), SCOPA-Sleep, Beck's Depression Inventory (BDI) questionnaire, Parkinson's Disease Questionnaire-8 questions (PDQ-8), SCOPA-Motor, SCOPA-Psychiatric Complications (SCOPA-PC), SCOPA-Cognition (SCOPA-COG), Mini-Mental State Examination (MMSE), Hoehn and Yahr Staging (H and Y), and Unified Parkinson Disease Rating Scale (UPDRS).

Results: 186 patients were enrolled (mean age 64.46 ± 9.9 years; disease duration 5.59 ± 3.99 years; 118 (63.4%) male; mean NMSS score 52.01 ± 38.54). Neither the floor effect (2.7%) nor the ceiling effect (0.5%) was seen in NMSS total score. Cronbach's alpha of total NMSS was 0.84. The test-retest reliability was 0.93 for the NMSS total and 0.81-0.96 for domains. The standard error of measurement (SEM) was lower than half of the standard deviation for NMSS total and all domains. NMSS total showed a high correlation with UPDRS I (r_s = 0.84), UPDRS II (r_s = 0.58), PDQ-8 (r_s = 0.61), BDI (r_s = 0.71), SCOPA-sleep (r_s = 0.60), and SCOPA AUT (r_s = 0.66). NMSS has an acceptable discriminative validity based on disease duration and severity of disease according to H and Y staging.

Conclusion: The Persian NMSS is a valid and reliable measure for evaluating the burden of nonmotor symptoms in Iranian patients with PD.

Introduction: Despite remarkable progress in identifying Parkinson's disease (PD) genetic risk loci, the genetic basis of PD remains largely unknown. With the help of the endophenotype approach and using data from dopamine transporter single-photon emission computerized tomography (DaTscan), we identified potentially involved genes in PD.

Method: We conducted an imaging genetic study by performing exome-wide association study (EWAS) and genome-wide association study (GWAS) on the specific binding ratio (SBR) of six DaTscan anatomical areas between 489 and 559 subjects of Parkinson's progression markers initiative (PPMI) cohort and 83,623 and 36,845 single-nucleotide polymorphisms (SNPs)/insertion-deletion mutations (INDELs). We also investigated the association of cerebrospinal fluid (CSF) protein concentration of our significant genes with PD progression using PPMI CSF proteome data.

Results: Among 83,623 SNPs/INDELs in EWAS, one SNP (rs201465075) on 1 q32.1 locus was significantly (P value = 4.03 × 10^-7) associated with left caudate DaTscan SBR, and 33 SNPs were suggestive. Among 36,845 SNPs in GWAS, one SNP (rs12450112) on 17 p.12 locus was significantly (P value = 1.34 × 10^-6) associated with right anterior putamen DaTscan SBR, and 39 SNPs were suggestive among which 8 SNPs were intergenic. We found that rs201465075 and rs12450112 are most likely related to IGFN1 and MAP2K4 genes. The protein level of MAP2K4 in the CSF was significantly associated with PD progression in the PPMI cohort; however, proteomic data were not available for the IGFN1 gene.

Conclusion: We have shown that particular variants of IGFN1 and MAP2K4 genes may be associated with PD. Since DaTscan imaging could be positive in other Parkinsonian syndromes, caution should be taken when interpreting our results. Future experimental studies are also needed to verify these findings.

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.

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; p < 0.0001), 43.7% (264/604) at V1, and 48.2% (242/502) at V2 (3.2% (4/124) in controls; p < 0.0001), with a period prevalence of 63.6% (306/481). Being older (OR = 1.032; p = 0.012), being male (OR = 2.333; p < 0.0001), having greater nonmotor symptom (NMS) burden at the baseline (NMSS total score at V0; OR = 1.020; p < 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; p < 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; p = 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.

Background: Non-motor symptoms of Parkinson's disease (PD) such as cognitive impairment are common and decrease patient quality of life and daily functioning. While no pharmacological treatments have effectively alleviated these symptoms to date, non-pharmacological approaches such as cognitive remediation therapy (CRT) and physical exercise have both been shown to improve cognitive function and quality of life in people with PD.

Objective: This study aims to determine the feasibility and impact of remote CRT on cognitive function and quality of life in patients with PD participating in an organized group exercise program.

Methods: Twenty-four subjects with PD recruited from Rock Steady Boxing (RSB), a non-contact group exercise program, were evaluated using standard neuropsychological and quality of life measures and randomized to the control or intervention group. The intervention group attended online CRT sessions for one hour, twice a week for 10 weeks, engaging in multi-domain cognitive exercises and group discussion.

Results: Twenty-one subjects completed the study and were reevaluated. Comparing groups over time, the control group (n = 10) saw a decline in overall cognitive performance that trended towards significance (p = 0.05) and a statistically significant decrease in delayed memory (p = 0.010) and self-reported cognition (p = 0.011). Neither of these findings were seen in the intervention group (n = 11), which overwhelmingly enjoyed the CRT sessions and attested to subjective improvements in their daily lives.

Conclusions: This randomized controlled pilot study suggests that remote CRT for PD patients is feasible, enjoyable, and may help slow the progression of cognitive decline. Further trials are warranted to determine the longitudinal effects of such a program.

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 PD samples and 17 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: Parkinson's disease (PD) is the second most common neurological disorder. Patients with PD were affected by the COVID-19 pandemic in many different ways. This study's principal purpose is to assess PD patients' vulnerability to COVID-19 and its consequences.

Method: This systematic review was performed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines. A thorough search was conducted in the Medline (through PubMed) and Scopus databases from inception to January 30, 2022. The Joanna Briggs Institute (JBI) critical appraisal checklist was used to evaluate the studies.

Results: Most of the studies (38%) had been conducted in Italy. Of the total number of studies, 17 (58%) were cross-sectional, seven (22%) were cohort, four (12%) were quasiexperimental, two (6%) were case-control, and one (3%) was a qualitative study. The PD duration in patients ranged from 3.26 to 13.40 years (IQR1: 5.7 yrs., median: 3.688 yrs., and IQR3: 8.815 yrs.). Meanwhile, the sample size ranged from 12 to 30872 participants (IQR1: 46, median: 96, and IQR3: 211). Despite worsening PD symptoms in the targeted population (persons with COVID-19 and Parkinson's disease), some studies found PD to be a risk factor for more severe COVID-19 disease. There are many adverse effects during the pandemic period in PD patients such as abnormalities of motor, nonmotor functioning, clinical outcomes, activities of daily living, and other outcomes.

Conclusion: This study confirmed the negative effect of the COVID-19 pandemic on health-related quality of life and its determinants in patients with PD and their caregivers. Thus, due to the worsening symptoms of PD patients in the current pandemic, these people should be given more care and supervision to minimize their coronavirus exposure.

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.