Parkinson's Disease最新文献

Background: People with Parkinson's disease (PWP) and their care partners (CP) are underrepresented in research.

Methods: As an eight-week research advocacy training program, TeleDREAMS was designed to increase understanding of, and participation in, clinical research by older adults through topics on the research process. Qualitative analysis was conducted to explore themes from 365 thirty-minute semistructured phone interviews with 32 PWP and 17 CP TeleDREAMS participants. Interviews gauged progress, motivation, and information retention after each weekly module.

Results: Eight salient themes were identified from the interviews, including Understanding the Importance of Advocacy and Becoming Cognizant of Past Advocacy Experiences.

Conclusions: While some findings aligned with weekly module topics, others, such as stated learning preferences and knowledge acquisition of older adults in an educational program, were unexpected. TeleDREAMS may increase interest in community engagement, research participation, and advocacy roles in marginalized and underrepresented participants.

Background: Archery exercise exerts a rehabilitative effect on patients with paraplegia and might potentially serve as complementary physiotherapy for patients with Parkinson's disease.

Objective: This study aimed to examine the rehabilitative effects of an archery intervention.

Methods: A randomized controlled trial of a 12-week intervention was performed in patients with idiopathic Parkinson's disease. Thirty-one of the 39 eligible patients recruited from a medical center in Taiwan participated in the trial, of whom 16 were in the experimental group practicing archery exercises and 15 were in the control group at the beginning; twenty-nine completed the whole process. The Purdue pegboard test (PPT), the Unified Parkinson's Disease Rating Scale I to III (UPDRS I to III), physical fitness test, and timed up and go test (TUG) were used to assess the intervention effects of archery exercise.

Results: Compared to the control group, the outcome differences between the posthoc and baseline tests in PPT, UPDRS I to III, lower extremity muscular strength, and TUG in the experimental group (between-group difference in difference's mean: 2.07, 1.59, 1.36, -2.25, -3.81, -9.10, 3.57, and -1.51, respectively) did show positive changes and their effect sizes examined from Mann-Whitney U tests (η: 0.631, 0.544, 0.555, 0.372, 0.411, 0.470, 0.601, and 0.381, respectively; Ps < 0.05) were medium to large, indicating that the archery intervention exerted promising effects on improving hand flexibility and finger dexterity, activity functions in motor movement, lower extremity muscular strength, and gait and balance ability.

Conclusions: Traditional archery exercise was suggested to have a rehabilitative effect for mild to moderate Parkinson's disease and could be a form of physiotherapy. Nevertheless, studies with larger sample sizes and extended intervention periods are needed to ascertain the long-term effects of archery exercise.

Objective: To investigate the role of aberrant Dyrk1a expression in phosphorylation modification at the α-synuclein serine 129 (Ser129) site to analyze its molecular mechanism in mediating apoptosis of PD.

Methods: The protein level of P-α-synuclein (Ser129), α-synuclein, Bcl-2, Bax, active caspase 3, GSK3β, PI3K, AKT, and cyclinD1 were detected. The mRNA transcript levels of Dyrk1a and DAT and protein levels of IL-1β, IL-6, COX-2, and TNF-α were detected.

Results: P-α-synuclein (Ser129), α-synuclein, Bax, active caspase 3, GSK3β, and cyclinD1 expressions were decreased in Dyrk1a-AAV-ShRNA (P < 0.05), and Bcl-2, AKT, and PI3K expressions were increased (P < 0.05). Increased TH protein expression was shown in Dyrk1a-AAV-ShRNA (P < 0.05). Dyrk1a mRNA was decreased in the Dyrk1a-AAV-ShRNA group (P < 0.05), and DAT mRNA was increased (P < 0.05). IL-1β, IL-6, COX-2, and TNF-α protein levels were decreased in Dyrk1al-AAV-Sh-RNA (P < 0.05). Transcriptome sequencing showed that Fam220a, which was expected to activate STAT family protein binding activity and participate in the negative regulation of transcription through RNA polymerase II and protein dephosphorylation showed differentially upregulated expression. The untargeted metabolome showed that the major compounds in the Dyrk1a-AAV-ShRNA group were hormones and transmission mediators and the most metabolism-related pathways. Fam220a showed differentially upregulated expression, and differentially expressed genes were enriched for the neuroactive ligand-receptor interaction, vascular smooth muscle contraction, and melanogenesis-related pathways.

Conclusion: Abnormal Dyrk1a expression can affect α-synuclein phosphorylation modifications, and dyrk1a knockdown activates the PI3K/AKT pathway and reduces dopaminergic neuron apoptosis. It provides a theoretical basis for the group to further investigate the molecular mechanism.

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.

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.

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.

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.