Baseline prevalence and longitudinal evolution of non-motor symptoms in early Parkinson’s disease: the PPMI cohort

ObjectiveTo examine the baseline prevalence and longitudinal evolution in non-motor symptoms (NMS) in a prospective cohort of, at baseline, patients with de novo Parkinson’s disease (PD) compared with healthy controls (HC).MethodsParkinson’s Progression Markers Initiative (PPMI) is a longitudinal, ongoing, controlled study of de novo PD participants and HC. NMS were rated using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part I score and other validated NMS scales at baseline and after 2 years. Biological variables included cerebrospinal fluid (CSF) markers and dopamine transporter imaging.Results423 PD subjects and 196 HC were enrolled and followed for 2 years. MDS-UPDRS Part I total mean (SD) scores increased from baseline 5.6 (4.1) to 7.7 (5.0) at year 2 in PD subjects (p<0.001) versus from 2.9 (3.0) to 3.2 (3.0) in HC (p=0.38), with a significant difference between the groups (p<0.001). In the multivariate analysis, higher baseline NMS score was associated with female sex (p=0.008), higher baseline MDS-UPDRS Part II scores (p<0.001) and more severe motor phenotype (p=0.007). Longitudinal increase in NMS severity was associated with the older age (0.008) and lower CSF Aβ1–42 (0.005) at baseline. There was no association with the dose or class of dopaminergic therapy.ConclusionsThis study of NMS in early PD identified clinical and biological variables associated with both baseline burden and predictors of progression. The association of a greater longitudinal increase in NMS with lower baseline Aβ1–42 level is an important finding that will have to be replicated in other cohorts.Trial registrationClinicalTrials.gov identifier: NCT01141023.

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THE IMPACT OF BRAZILIAN SAMBA ON PARKINSON’S DISEASE: ANALYSIS BY THE DISEASE SUBTYPES

Revista Brasileira de Medicina do Esporte ◽

10.1590/1517-869220202601220640 ◽

2020 ◽

Vol 26 (1) ◽

pp. 25-29

Author(s):

Ana Cristina Tillmann ◽

Alessandra Swarowsky ◽

Alexandro Andrade ◽

Jéssica Moratelli ◽

Leonessa Boing ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Control Group ◽

Positive Trend ◽

Motor Symptoms ◽

Significant Difference ◽

Disease Subtypes ◽

The Impact ◽

Non Motor Symptoms

ABSTRACT Introduction: People with Parkinson's disease constantly have low levels of physical activity. Dancing has become increasingly important for treating the disease and can help improve non-motor symptoms. Objective: To analyze the influence of Brazilian samba on the non-motor symptoms of PD according to TD and PGID subtypes. Methods: A 12-week, non-randomized clinical trial, through comparison with a control group. The 23 individuals who agreed to participate in the activities formed the experimental group (EG) and the 24 individuals who opted not to participate in the Brazilian samba classes comprised the control group (CG). A questionnaire was applied, composed of validated instruments. Mini Mental State Examination – MMSE; HY – Disability Scale; Unified Parkinson's Disease Rating Scale – UPDRS 1 and total values; Parkinson's Disease Questionnaire – PDQ-39, Parkinson's Disease Sleep Scale – PDSS; Beck Depression Inventory – BDI; Fatigue Severity Scale – FSS and Magnitude of Perceived Changes. Results: After the twelve weeks of intervention, it was observed that the EG showed improvement in the scores of all the tests. The comparison between groups, however, indicated a significant difference in the post-UPDRS1 period in which the EG presented improvement in cognitive impairment, while the CG presented a deficit in these values. The results of the division between disease subtypes show a greater change in the values between individuals of the TD group, when comparing the EG with the CG. For the EG, the greatest difference between pre- and post- intervention was fatigue. Conclusion: There was a positive trend in all the variables studied after the application of the protocol. This demonstrates that interventions such as dance may have greater effects on non-motor symptoms, depending on the expected progression of the disease. The scarcity of studies that use this approach in their analyses may explain the lack of evidence in this symptomatology related to dance. Level of evidence II; Therapeutic studies – Investigating the results of treatment.

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A Dual Centre Study of Pain in Parkinson’s Disease and Its Relationship with Other Non-Motor Symptoms

Journal of Parkinson s Disease ◽

10.3233/jpd-202088 ◽

2020 ◽

Vol 10 (4) ◽

pp. 1817-1825

Author(s):

Pritha Ghosh ◽

Paola Imbriani ◽

Nicoletta Caputi ◽

Silvia Natoli ◽

Tommaso Schirinzi ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Clustering Algorithms ◽

Motor Symptom ◽

Sleep Disruption ◽

Motor Symptoms ◽

Cross Sectional ◽

Non Motor Symptoms ◽

Updrs Part

Background: Pain is a disabling and often underestimated non-motor symptom (NMS) detrimentally affecting the quality of life of patients with Parkinson’s disease (PD). Objective: Here, we conducted a cross-sectional, observational international study on 167 patients with idiopathic PD in order to analyze the potential relationship between pain and other NMS. Methods: Subjects were assessed with the Unified Parkinson’s Disease Rating Scale (UPDRS) part III, Hoehn and Yahr (H&Y) stage, King’s Parkinson’s Disease Pain Scale (KPPS), Brief Pain Inventory (BPI), Non-Motor Symptoms Scale (NMSS), and Beck Depression Inventory (BDI). Spearman’s rank correlation coefficient, multiple regression and multiple index-based clustering algorithms were used for data analysis. Results: The prevalence of pain was 88.6%, was not correlated with age, motor severity (UPDRS part III) or disease duration, whereas a weak correlation with female gender and H&Y stage >2.5 was found. Multiple NMS correlated significantly with pain. Specifically, sleep disturbance had the strongest correlation with pain, followed by depression, gastrointestinal and cardiovascular disturbances. Further analyses showed that sleep and cardiovascular disturbance were independently associated with pain, and that these symptoms clustered together in a subset of PD patients. The relationship between pain, sleep and dysautonomia persisted independently from dopamine replacement therapy. Conclusion: Our study suggests that sleep disruption and cardiovascular disturbance are associated with pain in PD, and possibly identifies a specific subtype within PD patients with pain. Our data also indicate that sleep disruption, pain and dysautonomia may have a common pathophysiology, possibly involving non-dopaminergic pathways.

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Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation

Microbial Cell Factories ◽

10.1186/s12934-021-01589-0 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Xiao-yi Kuai ◽

Xiao-han Yao ◽

Li-juan Xu ◽

Yu-qing Zhou ◽

Li-ping Zhang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Neurodegenerative Disorder ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Motor Symptoms ◽

Gastrointestinal Dysfunction ◽

Before And After ◽

Non Motor Symptoms

AbstractParkinson’s disease (PD) is a neurodegenerative disorder and 70–80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.

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Constipation is Associated with Development of Cognitive Impairment in de novo Parkinson’s Disease: A Longitudinal Analysis of Two International Cohorts

Journal of Parkinson s Disease ◽

10.3233/jpd-212570 ◽

2021 ◽

pp. 1-11

Author(s):

Valentina Leta ◽

Daniele Urso ◽

Lucia Batzu ◽

Daniel Weintraub ◽

Nataliya Titova ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

De Novo ◽

Motor Dysfunction ◽

Group Differences ◽

Motor Symptoms ◽

Kaplan Meier ◽

Patients At Risk ◽

Non Motor Symptoms

Background: Constipation is regarded as one of the prodromal features of Parkinson’s disease (PD) and there is emerging evidence linking gastrointestinal dysfunction and cognitive impairment (CI) in PD. Objective: We explored whether constipation is associated with development of CI in two independent cohorts of de novo PD patients (n = 196 from the Non-motor International Longitudinal Study [NILS] and n = 423 from the Parkinson’s Progression Markers Initiative [PPMI] study). Methods: Constipation was clinically defined using the Non-Motor Symptoms Scale (NMSS) item-21 [NILS] and Scales for Outcomes in PD-Autonomic (SCOPA-AUT) item-5 [PPMI]. We assessed baseline group differences (PD with or without constipation) in CI, global non-motor symptoms burden, motor dysfunction, and striatal dopaminergic denervation. Kaplan-Meier method estimated group differences in cumulative proportion of patients with incident CI over three years. In PPMI, we subsequently performed univariate and multivariate Cox survival analyses to evaluate whether constipation predicts incident mild cognitive impairment or dementia over a 6-year period, including constipation and other known predictors of CI as covariates. Results: Patients with constipation had greater motor and global non-motor burden in both cohorts at baseline (p < 0.05). Kaplan-Meier plots showed faster conversion to CI in patients with constipation in both cohorts (p < 0.05). In PPMI, 37 subjects developed dementia during a mean follow-up of 4.9 years, and constipation was an independent predictor of dementia onset (hazard ratio = 2.311; p = 0.02). Conclusion: Constipation in de novo PD patients is associated with development of cognitive decline and may serve as a clinical biomarker for identification of patients at risk for cognitive impairment.

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Dance Rhythms Improve Motor Symptoms in Individuals with Parkinson’s Disease: A Randomized Clinical Trial

Journal of Dance Medicine & Science ◽

10.12678/1089-313x.031522a ◽

2021 ◽

Author(s):

Jéssica A. Moratelli ◽

Kettlyn H. Alexandre ◽

Leonessa Boing ◽

Alessandra Swarowsky ◽

Clynton L. Corrêa ◽

...

Keyword(s):

Parkinson’S Disease ◽

Clinical Trial ◽

Parkinson's Disease ◽

Randomized Clinical Trial ◽

Rating Scale ◽

Freezing Of Gait ◽

Motor Symptoms ◽

Score Change ◽

Significant Difference ◽

Binary Group

Background: Evidence-based practices involving dance modalities found in binary (two-beat rhythm) or quaternary (four-beat rhythm) show that dance positively influences the motor aspects of disease.Aim: This randomized clinical trial aimed to analyze the effect of two dance rhythm (binary and quaternary) on the balance, gait, and mobility in individuals with Parkinson’s disease (PD). Methods: Thirty-one individuals with PD were randomized into the binary group (n = 18) and the quaternary group (n = 13). Both groups participated in different dance rhythms lasting 12 weeks, twice a week, for 45 minutes. Results: The binary group showed a significant difference in balance (p = 0.003), freezing of gait (p = 0.007), as well as in the motor aspects of MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), with emphasis on the total values with a score change of 3.23. In the quaternary group, significant differences were found in balance (p = 0.021) with a score change of -2.54 and in the motor aspects of the MDS-UPDRS Part III where the total values stood out with a change of 3.54. Discussion: When comparing the possible effects of binary and quaternary rhythms on the motor symptoms of individuals with PD, it was demonstrated that binary rhythm improved balance, freezing gait, and UPDRSIII. As for the quaternary rhythm, the benefits were in balance and the UPDRSIII. Conclusion: The binary and the quaternary rhythm dance protocols positively influenced the motor symptoms of individuals with PD after 12 weeks of intervention.

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Consistency and Stability of Motor Subtype Classifications in Patients With de novo Parkinson’s Disease

Frontiers in Neuroscience ◽

10.3389/fnins.2021.637896 ◽

2021 ◽

Vol 15 ◽

Author(s):

Jingru Ren ◽

Chenxi Pan ◽

Yuqian Li ◽

Lanting Li ◽

Ping Hua ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

De Novo ◽

Classification Systems ◽

Motor Symptoms ◽

Chi Squared ◽

Baseline Evaluation ◽

The Stability ◽

First Time ◽

Non Motor Symptoms

ObjectivePatients with Parkinson’s disease (PD) are commonly classified into subtypes based on motor symptoms. The aims of the present study were to determine the consistency between PD motor subtypes, to assess the stability of PD motor subtypes over time, and to explore the variables influencing PD motor subtype stability.MethodsThis study was part of a longitudinal study of de novo PD patients at a single center. Based on three different motor subtype classification systems proposed by Jankovic, Schiess, and Kang, patients were respectively categorized as tremor-dominant/indeterminate/postural instability and gait difficulty (TD/indeterminate/PIGD), TDS/mixedS/akinetic-rigidS (ARS), or TDK/mixedK/ARK at baseline evaluation and then re-assessed 1 month later. Demographic and clinical characteristics were recorded at each evaluation. The consistency between subtypes at baseline evaluation was assessed using Cohen’s kappa coefficient (κ). Additional variables were compared between PD subtype groups using the two-sample t-test, Mann–Whitney U-test or Chi-squared test.ResultsOf 283 newly diagnosed, untreated PD patients, 79 were followed up at 1 month. There was fair agreement between the Jankovic, Schiess, and Kang classification systems (κS = 0.383 ± 0.044, κK = 0.360 ± 0.042, κSK = 0.368 ± 0.038). Among the three classification systems, the Schiess classification was the most stable and the Jankovic classification was the most unstable. The non-motor symptoms questionnaire (NMSQuest) scores differed significantly between PD patients with stable and unstable subtypes based on the Jankovic classification (p = 0.008), and patients with a consistent subtype had more severe NMSQuest scores than patients with an inconsistent subtype.ConclusionFair consistency was observed between the Jankovic, Schiess, and Kang classification systems. For the first time, non-motor symptoms (NMSs) scores were found to influence the stability of the TD/indeterminate/PIGD classification. Our findings support combining NMSs with motor symptoms to increase the effectiveness of PD subtypes.

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The Add-On Effect of Lactobacillus plantarum PS128 in Patients With Parkinson's Disease: A Pilot Study

Frontiers in Nutrition ◽

10.3389/fnut.2021.650053 ◽

2021 ◽

Vol 8 ◽

Author(s):

Chin-Song Lu ◽

Hsiu-Chen Chang ◽

Yi-Hsin Weng ◽

Chiung-Chu Chen ◽

Yi-Shan Kuo ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Lactobacillus Plantarum ◽

Outcome Measures ◽

Rating Scale ◽

Controlled Trial ◽

Secondary Outcome ◽

Motor Deficits ◽

Motor Symptoms ◽

Non Motor Symptoms

Background:Lactobacillus plantarum PS128 (PS128) is a specific probiotic, known as a psychobiotic, which has been demonstrated to alleviate motor deficits and inhibit neurodegenerative processes in Parkinson's disease (PD)-model mice. We hypothesize that it may also be beneficial to patients with PD based on the possible mechanism via the microbiome-gut-brain axis.Methods: This is an open-label, single-arm, baseline-controlled trial. The eligible participants were scheduled to take 60 billion colony-forming units of PS128 once per night for 12 weeks. Clinical assessments were conducted using the Unified Parkinson's Disease Rating Scale (UPDRS), modified Hoehn and Yahr scale, and change in patient “ON-OFF” diary recording as primary outcome measures. The non-motor symptoms questionnaire, Beck depression inventory-II, patient assessment of constipation symptom, 39-item Parkinson's Disease Questionnaire (PDQ-39), and Patient Global Impression of Change (PGI-C) were assessed as secondary outcome measures.Results: Twenty-five eligible patients (32% women) completed the study. The mean age was 61.84 ± 5.74 years (range, 52–72), mean disease duration was 10.12 ± 2.3 years (range, 5–14), and levodopa equivalent daily dosage was 1063.4 ± 209.5 mg/daily (range, 675–1,560). All patients remained on the same dosage of anti-parkinsonian and other drugs throughout the study. After 12 weeks of PS128 supplementation, the UPDRS motor scores improved significantly in both the OFF and ON states (p = 0.004 and p = 0.007, respectively). In addition, PS128 intervention significantly improved the duration of the ON period and OFF period as well as PDQ-39 values. However, no obvious effect of PS128 on non-motor symptoms of patients with PD was observed. Notably, the PGI-C scores improved in 17 patients (68%). PS128 intervention was also found to significantly reduce plasma myeloperoxidase and urine creatinine levels.Conclusion: The present study demonstrated that PS128 supplementation for 12 weeks with constant anti-parkinsonian medication improved the UPDRS motor score and quality of life of PD patients. We suggest that PS128 could serve as a therapeutic adjuvant for the treatment of PD. In the future, placebo-controlled studies are needed to further support the efficacy of PS128 supplementation.Clinical Trial Registration:https://clinicaltrials.gov/, identifier: NCT04389762.

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Association between White Matter Lesions and Non-Motor Symptoms in Parkinson Disease

Neurodegenerative Diseases ◽

10.1159/000489311 ◽

2018 ◽

Vol 18 (2-3) ◽

pp. 127-132 ◽

Cited By ~ 3

Author(s):

Jeong-Yoon Lee ◽

Ji Sun Kim ◽

Wooyoung Jang ◽

Jinse Park ◽

Eungseok Oh ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

White Matter ◽

Parkinson Disease ◽

Cognitive Dysfunction ◽

Rating Scale ◽

White Matter Lesions ◽

Motor Dysfunction ◽

Motor Symptoms ◽

Non Motor Symptoms

Background: There are only few studies exploring the relationship between white matter lesions (WMLs) and non-motor symptoms in Parkinson disease (PD). This study aimed to investigate the association between WMLs and the severity of non-motor symptoms in PD. Methods: The severity of motor dysfunction, cognitive impairment, and non-motor symptoms was assessed by various scales in 105 PD patients. We used a visual semiquantitative rating scale and divided the subjects into four groups: no, mild, moderate, and severe WMLs. We compared the means of all scores between the four groups and analyzed the association between the severity of WMLs and the specific domain of non-motor symptoms. Results: The non-motor symptoms as assessed by the Non-Motor Symptoms Scale, Parkinson’s Disease Questionnaire (PDQ-39), Parkinson’s Disease Sleep Scale, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Neuropsychiatric Inventory (NPI), and Parkinson Fatigue Scale (PFS) were significantly worse in the patients with moderate and severe WMLs than in those without WMLs. Compared with the no WML group, the scores for motor dysfunction were significantly higher in the mild, moderate, and severe WML groups. The scores for cognitive dysfunction were significantly higher in the patients with severe WMLs than in those without WMLs. The severity of WMLs showed linear associations with PFS, BDI, BAI, NPI, and PDQ-39 scores. The severity of WMLs also correlated linearly with scores for motor and cognitive dysfunction. Conclusions: Among the non-motor symptoms, fatigue, depression, anxiety, and quality of life were significantly affected by WMLs in PD. Confirmation of the possible role of WMLs in non-motor symptoms associated with PD in a prospective manner may be crucial not only for understanding non-motor symptoms but also for the development of treatment strategies.

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