Journal of Parkinson's Disease - Volume 11, issue 4

Authors: Manna, Ida | Quattrone, Andrea | De Benedittis, Selene | Iaccino, Enrico | Quattrone, Aldo

Article Type: Review Article

Abstract: Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting 5%of the elderly population. Currently, the diagnosis of PD is mainly based on clinical features and no definitive diagnostic biomarkers have been identified. The discovery of biomarkers at the earliest stages of PD is of extreme interest. This review focuses on the current findings in the field of circulating non-coding RNAs in PD. We briefly describe the more established circulating biomarkers in PD and provide a more thorough review of non-coding RNAs, in particular microRNAs, long non-coding RNAs and circular RNAs, differentially expressed in PD, highlighting their potential for …being considered as biomarkers for diagnosis. Together, these studies hold promise for the use of peripheral biomarkers for the diagnosis of PD. Show more

Keywords: Biomarkers, circular RNAs, long non-coding RNAs, microRNAs, noncoding RNAs, Parkinson’s disease

DOI: 10.3233/JPD-212726

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1475-1489, 2021

Authors: Yemula, Nehal | Dietrich, Celina | Dostal, Vaclav | Hornberger, Michael

Article Type: Review Article

Abstract: Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, characterized by symptoms of bradykinesia, rigidity, postural instability, and tremor. Recently, there has been a growing focus on the relationship between the gut and the development of PD. Emerging to the forefront, an interesting concept has developed suggesting that the initial pathophysiological changes occur in the gastrointestinal tract before changes are seen within the brain. This review is aimed at highlighting the relationship between PD and the gastrointestinal tract, along with the supporting evidence for this. Firstly, we will focus on the gastrointestinal conditions and symptoms which commonly affects …patients, including both upper and lower gastrointestinal issues. Secondly, the impact of nutrition and diet on neurological health and PD physiology, with particular emphasis on commonly consumed items including macronutrients and micronutrients. Finally, variability of the gut microbiome will also be discussed and its link with both the symptoms and signs of PD. The evidence presented in this review highly suggests that the initial pathogenesis in the gut may proceed the development of prodromal PD subtypes, and therefore building on this further could be imperative and lead to earlier diagnosis with new and improved therapeutics. Show more

Keywords: Gut, microbiota, nutrition, Parkinson’s disease

DOI: 10.3233/JPD-212707

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1491-1505, 2021

Authors: Auffret, Manon | Meuric, Vincent | Boyer, Emile | Bonnaure-Mallet, Martine | Vérin, Marc

Article Type: Review Article

Abstract: Despite clinical evidence of poor oral health and hygiene in Parkinson’s disease (PD) patients, the mouth is often overlooked by both patients and the medical community, who generally focus on motor or psychiatric disorders considered more burdensome. Yet, oral health is in a two-way relationship with overall health—a weakened status triggering a decline in the quality of life. Here, we aim at giving a comprehensive overview of oral health disorders in PD, while identifying their etiologies and consequences. The physical (abnormal posture, muscle tone, tremor, and dyskinesia), behavioral (cognitive and neuropsychiatric disorders), and iatrogenic patterns associated with PD have an …overall detrimental effect on patients’ oral health, putting them at risk for other disorders (infections, aspiration, pain, malnutrition), reducing their quality of life and increasing their isolation (anxiety, depression, communication issues). Interdisciplinary cooperation for prevention, management and follow-up strategies need to be implemented at an early stage to maintain and improve patients’ overall comfort and condition. Recommendations for practice, including (non-)pharmacological management strategies are discussed, with an emphasis on the neurologists’ role. Of interest, the oral cavity may become a valuable tool for diagnosis and prognosis in the near future (biomarkers). This overlooked but critical issue requires further attention and interdisciplinary research. Show more

Keywords: Parkinson’s disease, oral health, stomatognathic diseases, dentistry, microbiota, interdisciplinary research

DOI: 10.3233/JPD-212605

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1507-1535, 2021

Authors: Zaman, Muhammed Shahriar | Ghahari, Setareh | McColl, Mary Ann

Article Type: Review Article

Abstract: Parkinson’s disease is a complex condition that affects many different aspects of a person’s health. Because of its complexity, people with Parkinson’s disease require access to a variety of healthcare services. The aim of the present study was to identify the barriers to access healthcare services for people with Parkinson’s disease. We conducted a scoping review according to guidelines posed by Arksey & O’Malley (2005). A search of MEDLINE, Embase, CINHAL, and PsycINFO databases was conducted, and 38 articles were selected based on the inclusion criteria. The review findings identified person-level and system-level barriers. The person-level barriers included skills required …to seek healthcare services, ability to engage in healthcare and cost for services. The system-level barriers included the availability of appropriate healthcare resources. Based on the existing barriers elucidated in the scope review, we have discussed potential areas in healthcare that require improvement for people with Parkinson’s disease to manage their healthcare needs more equitably. Show more

Keywords: Parkinson’s disease, access barriers, healthcare services

DOI: 10.3233/JPD-212735

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1537-1553, 2021

Authors: Polinski, Nicole K.

Article Type: Review Article

Abstract: The use of wildtype recombinant alpha-synuclein preformed fibrils (aSyn PFFs) to induce endogenous alpha-synuclein to form pathological phosphorylation and trigger neurodegeneration is a popular model for studying Parkinson’s disease (PD) biology and testing therapeutic strategies. The strengths of this model lie in its ability to recapitulate the phosphorylation/aggregation of aSyn and nigrostriatal degeneration seen in PD, as well as its suitability for studying the progressive nature of PD and the spread of aSyn pathology. Although the model is commonly used and has been adopted by many labs, variability in observed phenotypes exists. Here we provide summaries of the study design …and reported phenotypes from published reports characterizing the aSyn PFF in vivo model in rodents following injection into the brain, gut, muscle, vein, peritoneum, and eye. These summaries are designed to facilitate an introduction to the use of aSyn PFFs to generate a rodent model of PD—highlighting phenotypes observed in papers that set out to thoroughly characterize the model. This information will hopefully improve the understanding of this model and clarify when the aSyn PFF model may be an appropriate choice for one’s research. Show more

Keywords: Alpha-synuclein, Parkinson disease, preformed fibril, model

DOI: 10.3233/JPD-212847

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1555-1567, 2021

Authors: Maple-Grødem, Jodi | Paul, Kimberly C. | Dalen, Ingvild | Ngo, Kathie J. | Wong, Darice | Macleod, Angus D. | Counsell, Carl E. | Bäckström, David | Forsgren, Lars | Tysnes, Ole-Bjørn | Kusters, Cynthia D.J. | Fogel, Brent L. | Bronstein, Jeff M. | Ritz, Beate | Alves, Guido

Article Type: Position Paper

Abstract: Background: Motor complications are a consequence of the chronic dopaminergic treatment of Parkinson’s disease (PD) and include levodopa-induced dyskinesia (LIDs) and motor fluctuations (MF). Currently, evidence is on lacking whether patients with GBA -associated PD differ in their risk of developing motor complications compared to the general PD population. Objective: To evaluate the association of GBA carrier status with the development of LIDS and MFs from early PD. Methods: Motor complications were recorded prospectively in 884 patients with PD from four longitudinal cohorts using part IV of the UPDRS or MDS-UPDRS. Subjects were followed for …up to 11 years and the associations of GBA mutations with the development of motor complications were assessed using parametric accelerated failure time models. Results: In 439 patients from Europe, GBA mutations were detected in 53 (12.1%) patients and a total of 168 cases of LIDs and 258 cases of MF were observed. GBA carrier status was not associated with the time to develop LIDs (HR 0.78, 95%CI 0.47 to 1.26, p  = 0.30) or MF (HR 1.19, 95%CI 0.84 to 1.70, p  = 0.33). In the American cohorts, GBA mutations were detected in 36 (8.1%) patients and GBA carrier status was also not associated with the progression to LIDs (HR 1.08, 95%CI 0.55 to 2.14, p  = 0.82) or MF (HR 1.22, 95%CI 0.74 to 2.04, p  = 0.43). Conclusion: This study does not provide evidence that GBA -carrier status is associated with a higher risk of developing motor complications. Publication of studies with null results is vital to develop an accurate summary of the clinical features that impact patients with GBA -associated PD. Show more

Keywords: GBA, Parkinson’s disease, motor complications, dyskinesias, motor fluctuations

DOI: 10.3233/JPD-212657

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1569-1578, 2021

Authors: Ineichen, Christian | Baumann-Vogel, Heide | Sitzler, Matthias | Waldvogel, Daniel | Baumann, Christian R.

Article Type: Short Communication

Abstract: Whilst some studies investigated the impact of viral infection or reduced access to medication during the COVID-19 pandemic in patients with Parkinson’s disease (PD), data on the effects of pandemic restrictions are still scarce. We retrospectively analyzed motor symptoms of longitudinally followed PD patients (n  = 264) and compared motor disease progression before and during the COVID-19 pandemic. Additionally, we performed a trend analysis of the yearly evolution of motor symptoms in 755 patients from 2016 until 2021. We observed a worsening of motor symptoms and a significantly increased motor disease progression during pandemic-related restrictions as compared to before the COVID-19 …outbreak. Show more

Keywords: Parkinson’s disease, COVID-19, confinement, motor disease progression, MDS-UPDRS part III

DOI: 10.3233/JPD-212779

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1579-1583, 2021

Authors: Komici, Klara | Femminella, Grazia Daniela | Bencivenga, Leonardo | Rengo, Giuseppe | Pagano, Gennaro

Article Type: Research Article

Abstract: Background: A link between diabetes mellitus (DM) and Parkinson’s disease (PD) have been proposed but evidence are sparse and inconsistent. Objective: Perform a systematic review of all evidence that link DM and PD characterising the prevalence of DM in PD patients, the risk of developing PD in DM patients and the influence of DM on PD severity and progression. Methods: MEDLINE, Scopus, and Cochrane Library from inception to June 30, 2021 were searched. Studies reporting prevalence, incidence, severity and disease progression of DM and PD were included. Prevalence of DM in PD and incidence of PD …in DM patients, and characteristics of PD. Results: A total of 21 studies (n  = 11,396) included data on DM prevalence in PD patients, 12 studies (n  = 17,797,221) included data on incidence of PD in DM patients, and 10 studies (n  = 2,482) included data on DM impact on PD severity and disease progression. The prevalence of DM in PD patients was 10.02 %, (95%C.I. 7.88 –12.16), DM patients showed a higher risk of developing PD (OR: 1.34 95%CI 1.26–1.43 p  < 0.0001) compared to non-DM, and PD patients with DM showed a greater severity of motor symptoms, with higher Hoehn and Yahr stage (SMD: 0.36 95%CI 0.12–0.60; p  < 0.001) and higher UPDRS (SMD 0.60 95%CI 0.28–0.92; p  < 0.001) compared with PD patients without DM. Conclusion: Although the prevalence of DM in PD patients is similar to the general population, patients with DM have a higher risk of developing PD, and the presence of DM is associated with greater PD severity and faster progression, which suggests that DM may be a facilitating factor of neurodegeneration. Show more

Keywords: Parkinson’s disease, diabetes mellitus, hyperglycaemia, insulin sensitivity, neurodegeneration

DOI: 10.3233/JPD-212725

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1585-1596, 2021

Authors: Tan, Qian Yue | Cox, Natalie J. | Lim, Stephen E.R. | Coutts, Laura | Fraser, Simon D.S. | Roberts, Helen C. | Ibrahim, Kinda

Article Type: Research Article

Abstract: Background High treatment burden is associated with poor adherence, wasted resources, poor quality of life and poor health outcomes. Identifying factors that impact treatment burden in Parkinson’s disease can offer insights into strategies to mitigate them. Objective To explore the experiences of treatment burden among people with Parkinson’s disease (PwP) and their caregivers. Methods A systematic review of studies published from year 2006 was conducted. Qualitative and mixed-method studies with a qualitative component that relate to usual care in Parkinson’s disease were included. Quantitative studies and grey literature were excluded. Data synthesis was conducted using framework …synthesis. Results 1757 articles were screened, and 39 articles included. Understanding treatment burden in PwP and caregivers was not the primary aim in any of the included studies. The main issues of treatment burden in Parkinson’s disease are: 1) work and challenges of taking medication; 2) healthcare provider obstacles including lack of patient-centered care, poor patient-provider relationships, lack of care coordination, inflexible organizational structures, lack of access to services and issues in care home or hospital settings; and 3) learning about health and challenges with information provision. The treatment burden led to physical and mental exhaustion of self-care and limitations on the role and social activities of PwP and caregivers. Conclusion: There are potential strategies to improve the treatment burden in Parkinson’s disease at an individual level such as patient-centered approach to care, and at system level by improving access and care coordination between services. Future research is needed to determine the modifiable factors of treatment burden in Parkinson’s disease. Show more

Keywords: Treatment burden, burden of treatment, Parkinson’s disease, caregivers, review, qualitative, experience

DOI: 10.3233/JPD-212612

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1597-1617, 2021

Authors: Okada, Yohei | Ohtsuka, Hiroyuki | Kamata, Noriyuki | Yamamoto, Satoshi | Sawada, Makoto | Nakamura, Junji | Okamoto, Masayuki | Narita, Masaru | Nikaido, Yasutaka | Urakami, Hideyuki | Kawasaki, Tsubasa | Morioka, Shu | Shomoto, Koji | Hattori, Nobutaka

Article Type: Research Article

Abstract: Background: Long-term physiotherapy is acknowledged to be crucial to manage motor symptoms for Parkinson’s disease (PD) patients, but its effectiveness is not well understood. Objective: This systematic review and meta-analysis aimed to assess the evidence regarding the effectiveness of long-term physiotherapy to improve motor symptoms and reduce antiparkinsonian medication dose in PD patients. Methods: Pubmed, Cochrane, PEDro, and CINAHL were searched for randomized controlled trials before August 31, 2020 that investigated the effectiveness of physiotherapy for 6 months or longer on motor symptoms and levodopa-equivalent dose (LED) in PD patients with Hoehn and Yahr stage 1– …3. We performed random effects meta-analyses for long-term physiotherapy versus no/control intervention and estimated standard mean differences with 95% confidence intervals (CIs). Levels of evidence were rated by the Grading of Recommendation Assessment, Development and Evaluation approach. Results: From 2,940 studies, 10 studies involving 663 PD patients were assessed. Long-term physiotherapy had favorable effects on motor symptoms in off medication state [– 0.65, 95% CI – 1.04 to – 0.26, p  = 0.001] and LED [– 0.49, 95% CI – 0.89 to – 0.09, p  = 0.02]. Subgroup analyses demonstrated favorable effects on motor symptoms in off medication state by aerobic exercise [– 0.42, 95% CI – 0.64 to – 0.20, p  < 0.001] and LED by multidisciplinary rehabilitation of primarily physiotherapy [– 1.00, 95% CI – 1.44 to – 0.56, p  < 0.001]. Quality of evidence for aerobic exercise and multidisciplinary rehabilitation were low and very low. Conclusion: This review provided evidence that long-term physiotherapy has beneficial impact on motor symptoms and antiparkinsonian medication dose in PD patients and could motivate implementation of long-term physiotherapy. Show more

Keywords: Physiotherapy, Parkinson’s disease, motor symptoms, randomized controlled trial, systematic review, meta-analysis

DOI: 10.3233/JPD-212782

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1619-1630, 2021