Journal of Parkinson's Disease - Volume 10, issue 1

Authors: Bloem, Bastiaan R. | Brundin, Patrik

Article Type: Editorial

Keywords: Parkinson’s disease, research, clinical care, innovation

DOI: 10.3233/JPD-199006

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 1-3, 2020

Authors: Prakash, Neha | McFarthing, Kevin | Simuni, Tanya

Article Type: Other

DOI: 10.3233/JPD-199005

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 5-17, 2020

Authors: The International Parkinson Disease Genomics Consortium (IPDGC)

Article Type: Review Article

Abstract: In June 2009 a small group of investigators met at the annual Movement Disorders Society meeting in Paris. The explicit goal of this meeting was to discuss a potential research alliance focused on the genetics of Parkinson disease (PD). The outcome of this informal meeting was the creation of the International Parkinson Disease Genomics Consortium (IPDGC), a group focused on collaborative genetics research, enabled by trust, sharing, and as little paperwork as possible. The IPDGC has grown considerably since its inception, including over 100 scientists from around the World. The focus has also grown, to include clinical and functional investigation …of PD at scale. Most recently, the IPDGC has expanded to initiate major research efforts in East Asia and Africa, and has prioritized collaborations with ongoing major efforts in India and South America. Here we summarize the efforts of the IPDGC thus far and place these in the context of a decade of progress in PD genomics. We also discuss the future direction of IPDGC and our stated research priorities for the next decade. Show more

Keywords: IPDGC, Parkinson disease, genetics, genomics

DOI: 10.3233/JPD-191854

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 19-30, 2020

Authors: Ben-Joseph, Aaron | Marshall, Charles R. | Lees, Andrew J. | Noyce, Alastair J.

Article Type: Review Article

Abstract: The global prevalence of Parkinson’s disease is increasing, yet the characteristics, risk factors and genetics of PD in Black, Asian and Hispanic populations is little understood. In this paper we review the published literature on clinical variation in the symptoms and signs of Parkinson’s disease in different ethnic groups and responses to treatment. We included any study that sampled patients with Parkinson’s disease from distinct ethnic backgrounds. We conclude that whilst there is little published evidence for ethnic variation in the clinical features of Parkinson’s disease, there are substantial limitations and gaps in the current literature, which mean that the …evidence does necessarily not fit with clinical observation. Possible explanations for expected differences in manifestation include genetic determinants, the co-existence of cerebrovascular disease and/or Alzheimer’s disease pathology, healthcare inequalities and socio-cultural factors. Show more

Keywords: Parkinson’s disease, ethnic groups, epidemiology, tremor, dementia, atypical parkinsonism

DOI: 10.3233/JPD-191763

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 31-45, 2020

Authors: Svaerke, Katrine | Niemeijer, Miriam | Løkkegaard, Annemette

Article Type: Systematic Review

Abstract: Background: Deterioration of working memory(WM) is a common cognitive deficit in Parkinson’s disease (PD), and severely influences the ability to lead an independent life. Interventions which can delay the impact of WM deficits could positively impact the independence and quality of life of patients. Objective: To evaluate effects of computer-based cognitive rehabilitation (CBCR) on WM in patients with PD. Methods: Pubmed, Embase, Psycinfo and Cochrane Library were systematically searched. Authors of included studies were contacted to detect unpublished data or articles not found by database-search. Broad selection criteria were applied because literature was expected to be …limited. Studies were eligible for inclusion if they investigated the effects of CBCR on WM in a sample consisting of at least 50% PD patients, or in which the results of PD patients could be isolated. Studies were further eligible for inclusion in a planned meta-analysis if the effects of the CBCR intervention could be isolated, the CBCR intervention was compared to active or passive control groups consisting solely of PD patients, and the WM outcome measure could be isolated. Results: Only six studies were included despite broad inclusion criteria. Study results were heterogeneous, and the risk of bias in study methodology was either unclear or high. Two studies were eligible for meta-analysis. A meta-analysis was not performed, because these studies used different measures of WM which were not rated as equally valid and reliable. Conclusion: Existing literature is sparse and provides insufficient evidence to conclude if CBCR benefits WM in PD patients. Show more

Keywords: Parkinson’s disease, cognitive rehabilitation, computer-based cognitive rehabilitation, working memory, executive functions, systematic review

DOI: 10.3233/JPD-191726

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 47-57, 2020

Authors: Carroll, Louise M. | Morris, Meg E. | O’Connor, William T. | Clifford, Amanda M.

Article Type: Systematic Review

Abstract: Background: Aquatic therapy offers an alternative physiotherapy approach to managing the motor and non-motor symptoms associated with Parkinson’s disease (PD). Objective: This review examined exercise prescription for aquatic therapy in PD and evaluated if aquatic therapy is as effective as land-based physiotherapy for improving movement, disability and wellbeing in people living with PD. Methods: A systematic search of eight databases was conducted to identify suitable randomized controlled trials from inception until August 2019. Aquatic therapy prescription data and outcomes of interest included gait, balance, motor disability, mobility, falls, mood, cognitive function and health related quality of …life data was extracted and synthesised. A meta-analysis was performed where appropriate. Results: Fourteen studies involving 472 participants (Hoehn & Yahr scale I–IV) met the inclusion criteria. Eight were of modest quality, scoring 70–80% on the PEDro scale. Seven studies were included in the meta-analysis. Exercise prescription was highly variable and often insufficiently dosed. Similar gains were shown for aquatic therapy and land exercises for balance, motor disability or quality of life. A statistically significant difference was found for mobility as measured using the TUG (–1.5 s, 95 % CI –2.68 to –0.32; p  = 0.01, I2  = 13%), in favor of aquatic therapy. Conclusion: Aquatic therapy had positive outcomes for gait, balance and mobility that were comparable to land-based physiotherapy in the early stages of PD. The optimal dosage, content and duration of aquatic interventions for PD could not be confirmed in this meta-analysis. Many trials appeared to be under-dosed and therapy duration was low, ranging from 3–11 weeks. Show more

Keywords: Exercise, hydrotherapy, Parkinson’s disease, rehabilitation, review

DOI: 10.3233/JPD-191784

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 59-76, 2020

Authors: Chen, Chih-Hao | Lee, Bo-Ching | Lin, Chin-Hsien

Article Type: Research Article

Abstract: Background/Objective: Easily accessible biomarkers are crucial for disease-modifying clinical trials in patients with Parkinson’s disease (PD). We investigated integrated plasma and neuroimaging biomarkers correlating with motor and cognitive severity in PD patients. Methods: This cross-sectional study enrolled 170 participants (12 controls and 158 PD patients). Plasma α -synuclein and neurofilament light chain (NfL) level, and global and regional cortical thickness (CTh) on brain MRI were analyzed to predict advanced motor stage (Hoehn & Yahr stage ≥3), and PD dementia (PDD, MMSE score <26). Results: Plasma α -synuclein and NfL levels were higher in PD patients than …controls (both P  < 0.0001 for α -synuclein and NfL). Plasma NfL levels were significantly elevated in patients with advanced motor stage (P  = 0.008) or PDD; α -synuclein was elevated in the advanced motor stage group. Global CTh was thinner in patients with PDD than controls (2.33±0.19 mm vs 2.43±0.14 mm, P  = 0.06). Among PD patients, higher α -synuclein was associated with thinner limbic CTh, whereas higher NfL was associated with thinner temporal CTh and insular CTh. The accuracy of predicting advanced motor stage using age and sex alone (area under the curve [AUC] 0.63) was significantly improved by the addition of plasma α -synuclein and NfL, and temporal and insula CTh (full model, AUC 0.77, P  = 0.004). The accuracy of predicting PDD using age and sex alone (AUC 0.82) increased by incorporating plasma α -synuclein and NfL, and temporal and insula CTh as full model (AUC 0.87, P  = 0.047). Conclusions: Integrated plasma and neuroimaging biomarkers reflect both motor and cognitive aspects of PD severity. Show more

Keywords: Parkinson’s disease, biomarker, α-synuclein, neurofilament light chain, cognitive decline, dementia

DOI: 10.3233/JPD-191766

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 77-88, 2020

Authors: Cattaneo, Carlo | Jost, Wolfgang H. | Bonizzoni, Erminio

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is characterized by a wide range of motor and non-motor symptoms. Levodopa is still the most effective drug; however, its long-term use is associated with motor complications which may deteriorate patient’s quality of life. Safinamide is a unique treatment modulating both dopaminergic and glutamatergic systems. Previous results from two six months, double-blind, placebo-controlled studies demonstrated that safinamide has positive effects on both motor functions and quality of life in PD patients. Objective: To investigate the effects of safinamide 100 mg/day over two-year treatment on PD symptoms severity and quality of life, using data from the …study 018. Methods: Data from 352 patients were analyzed to evaluate the effects of safinamide on OFF time and ON time (with no or non-troublesome dyskinesia) in the overall population and in subgroups of patients (receiving levodopa monotherapy or with other anti-Parkinson therapies), and the effects of safinamide on motor symptoms/clinical fluctuations (by means of UPDRS III and IV) and on health-related quality of life (using UPDRS II and PDQ-39 summary index score). Results: Safinamide, administered as add-on to standard therapy in fluctuating PD patients, significantly improved motor symptoms and clinical fluctuations in the overall population and in some subgroups of patients. Additionally, safinamide improved quality of life and activities of daily living, maintaining the efficacy in the long-term. Conclusions: The findings of these analyses suggest that safinamide may be considered an appropriate adjunct therapy in patient not sufficiently controlled. Further investigations are desirable to confirm these results in usual care setting. Show more

Keywords: Parkinson’s disease, safinamide, MAO-B inhibitor, quality of life, motor fluctuations, glutamate, adjunct therapy

DOI: 10.3233/JPD-191765

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 89-97, 2020

Authors: Mursaleen, Leah | Somavarapu, Satyanarayana | Zariwala, Mohammed Gulrez

Article Type: Research Article

Abstract: Background: Reduced glutathione and excess free iron within dopaminergic, substantia nigra neurons in Parkinson’s disease (PD) can drive accumulation of toxic hydroxyl radicals resulting in sustained oxidative stress and cellular damage. Factors such as brain penetrance and bioavailability have limited the advancement of potential antioxidant and iron chelator therapies for PD. Objective: This study aimed to develop novel nanocarrier delivery systems for the antioxidant curcumin and/or iron chelator deferoxamine (DFO) to protect against rotenone-induced changes in cell viability and oxidative stress in SH-SY5Y cells. Methods: Nanocarriers of curcumin and/or DFO were prepared using Pluronic F68 (P68) …with or without dequilinium (DQA) by modified thin-film hydration. Cell viability was assessed using an MTT assay and oxidative stress was measured using thiobarbituric acid reactive substances and cellular antioxidant activity assays. Results: All formulations demonstrated high encapsulation efficiency (65–96%) and nanocarrier size was <200 nm. 3-h pretreatment with P68 or P68+DQA nanocarriers containing various concentrations of curcumin and/or DFO significantly protected against rotenone-reduced cell viability. The addition of DFO to curcumin-loaded P68+DQA nanocarriers resulted in increased protection by at least 10%. All nanoformulations significantly protected against rotenone-induced lipid peroxidation (p  < 0.0001). The addition of DQA, which targets mitochondria, resulted in up to 65% increase in cellular antioxidant activity. In nearly all preparations, the combination of 10 μM curcumin and 100 μM DFO had the most antioxidant activity. Conclusion: This study demonstrates for the first time the formulation and delivery using P68 and P68+DQA curcumin and/or DFO nanocarriers to protect against oxidative stress induced by a rotenone PD model. This strategy to combine antioxidants with iron chelators may provide a novel approach to fully utilise their therapeutic benefit for PD. Show more

Keywords: Parkinson’s disease, nanotechnology, curcumin, deferoxamine, oxidative stress

DOI: 10.3233/JPD-191754

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 99-111, 2020

Authors: Di Lazzaro, Giulia | Ricci, Mariachiara | Al-Wardat, Mohammad | Schirinzi, Tommaso | Scalise, Simona | Giannini, Franco | Mercuri, Nicola B. | Saggio, Giovanni | Pisani, Antonio

Article Type: Research Article

Abstract: Background: Technology-based objective measures (TOMs) recently gained relevance to support clinicians in the assessment of motor function in Parkinson’s disease (PD), although limited data are available in the early phases. Objective: To assess motor performances of a population of newly diagnosed, drug free PD patients using wearable inertial sensors and to compare them to healthy controls (HC) and differentiate different PD subtypes [tremor dominant (TD), postural instability gait disability (PIGD), and mixed phenotype (MP)]. Methods: We enrolled 65 subjects, 36 newly diagnosed, drug-free PD patients and 29 HCs. PD patients were clinically defined as tremor dominant, …postural instability-gait difficulties or mixed phenotype. All 65 subjects performed seven MDS-UPDRS III motor tasks wearing inertial sensors: rest tremor, postural tremor, rapid alternating hand movement, foot tapping, heel-to-toe tapping, Timed-Up-and-Go test (TUG) and pull test. The most relevant motor tasks were found combining ReliefF ranking and Kruskal– Wallis feature-selection methods. We used these features, linked to the relevant motor tasks, to highlight differences between PD from HC, by means of Support Vector Machine (SVM) classifier. Furthermore, we adopted SVM to support the relevance of each motor task on the classification accuracy, excluding one task at time. Results: Motion analysis distinguished PD from HC with an accuracy as high as 97%, based on SVM performed with measured features from tremor and bradykinesia items, pull test and TUG. Heel-to-toe test was the most relevant, followed by TUG and Pull Test. Conclusions: In this pilot study, we demonstrate that the SVM algorithm successfully distinguishes de novo drug-free PD patients from HC. Surprisingly, pull test and TUG tests provided relevant features for obtaining high SVM classification accuracy, differing from the report of the experienced examiner. The use of TOMs may improve diagnostic accuracy for these patients. Show more

Keywords: Parkinson’s disease, technology-based outcome measures, wearable sensors, balance, bradykinesia, gait analysis

DOI: 10.3233/JPD-191758

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 113-122, 2020