Journal of Parkinson's Disease - Volume 8, issue 4

Authors: Deng, Hao | Fan, Kuan | Jankovic, Joseph

Article Type: Review Article

Abstract: Parkinson’s disease (PD) is a common neurodegenerative disease whose pathogenesis remains unknown. TMEM230 gene, encoding a transmembrane protein in secretory and recycling vesicle, has been recently identified as a novel disease-causing gene of autosomal dominant PD with Lewy pathology and typical clinical symptoms. Although its mutation and variants seem to be rare in PD patients, functional studies have indicated that TMEM230 protein probably plays an important role in secretory and recycling pathway and may be involved in Lewy pathological mechanism. Here we summarize current genetic and functional reports about TMEM230 and focus on its relation with PD.

Keywords: Genetics, Lewy bodies, Parkinson’s disease, TMEM230

DOI: 10.3233/JPD-181421

Citation: Journal of Parkinson’s Disease, vol. 8, no. 4, pp. 469-477, 2018

Authors: Li, Hong | Jiang, Houbo | Zhang, Boyang | Feng, Jian

Article Type: Review Article

Abstract: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. It is characterized by the degeneration of nigral dopaminergic (DA) neurons. While over 90% of cases are idiopathic, without a clear etiology, mutations in many genes have been linked to rare, familial forms of PD. It has been quite challenging to develop effective animal models of PD that capture salient features of PD. The discovery of induced pluripotent stem cells (iPSCs) makes it possible to generate patient-specific DA neurons to study PD. Here, we review the methods for the generation of iPSCs and discuss previous studies using iPSC-derived neurons from …monogenic forms of PD. These investigations have revealed several converging pathways that intersect with the unique vulnerabilities of human nigral DA neurons. With the rapid development in stem cell biology, it is possible to generate patient-specific neurons that will be increasingly similar to those in the brain of the patient. Combined with the ability to edit the genome to generate isogenic iPSCs, the generation and analysis of patient-specific midbrain DA neurons will transform PD research by providing a valuable tool for mechanistic study and drug discovery. Show more

Keywords: iPSC, pluripotent, stem cells, dopaminergic neurons, parkin, α-synuclein, PINK1, DJ-1, LRRK2, GBA

DOI: 10.3233/JPD-181353

Citation: Journal of Parkinson's Disease, vol. 8, no. 4, pp. 479-493, 2018

Authors: Darweesh, Sirwan K.L. | Raphael, Karen G. | Brundin, Patrik | Matthews, Helen | Wyse, Richard K. | Chen, Honglei | Bloem, Bastiaan R.

Article Type: Short Communication

Abstract: Recent epidemiological observations have drawn attention to the rapid rise in the burden caused by Parkinson’s disease over the past years, emphasizing that Parkinson’s disease is a matter of serious concern for our future generations. A recent report by Public Health England corroborates this message, by providing new insight on trends in deaths associated with neurological diseases in England between 2001 to 2014. The report indicates that mortality associated with Parkinson’s disease and related disorders increased substantially between 2001 and 2014. This trend is partially explained by increased longevity in the population. However, it is possible that changes in …exposure to risk factors, recent improvements in multidisciplinary care (leading to prolonged survival), and improved diagnostic awareness or improved registration also influenced the observed trend. Furthermore, patients with Parkinson’s disease and related disorders were found to die at an advanced age, and the majority die in a care home or hospital, despite a preponderant preference for many patients and their families to spend their last days at home. To combat these concerning observations, future efforts should be focused on providing resources for vulnerable elderly Parkinson patients, avoiding unplanned hospital admissions and out-of-home deaths as much as possible. Possible solutions include a community-based network of specifically trained allied health therapists, personal case managers for Parkinson patients, dedicated Parkinson nursing homes, and improved centralised support services from university clinics to regional community hospitals aimed at facilitating optimal wide-scale care delivery. Show more

Keywords: Parkinson’s disease, mortality, trends, epidemiology

DOI: 10.3233/JPD-181374

Citation: Journal of Parkinson's Disease, vol. 8, no. 4, pp. 495-498, 2018

Authors: Domingos, Josefa | Keus, Samyra H.J. | Dean, John | de Vries, Nienke M. | Ferreira, Joaquim J. | Bloem, Bastiaan R.

Article Type: Short Communication

Abstract: The evidence for physiotherapy is growing, showing a positive impact on functional activities involving gait, transfers and balance. Specific recommendations for physiotherapists, physicians and people with Parkinson’s disease were published in the European Physiotherapy Guideline for Parkinson’s disease. Here, we summarize the referral criteria, highlight the importance of accurate referral to specialized physiotherapists, and emphasize the potential benefits of expert care. As such, this paper offers very practical guidance for clinicians working with Parkinson’s disease patients and who consider physiotherapy treatments for their patients.

Keywords: Parkinson’s disease, European Physiotherapy Guideline for Parkinson disease, referral criteria, physiotherapy

DOI: 10.3233/JPD-181383

Citation: Journal of Parkinson’s Disease, vol. 8, no. 4, pp. 499-502, 2018

Authors: Arora, Siddharth | Visanji, Naomi P. | Mestre, Tiago A. | Tsanas, Athanasios | AlDakheel, Amaal | Connolly, Barbara S. | Gasca-Salas, Carmen | Kern, Drew S. | Jain, Jennifer | Slow, Elizabeth J. | Faust-Socher, Achinoam | Lang, Anthony E. | Little, Max A. | Marras, Connie

Article Type: Short Communication

Abstract: We investigate the potential association between leucine-rich repeat kinase 2 (LRRK2 ) mutations and voice. Sustained phonations (‘aaah’ sounds) were recorded from 7 individuals with LRRK2 -associated Parkinson’s disease (PD), 17 participants with idiopathic PD (iPD), 20 non-manifesting LRRK2 -mutation carriers, 25 related non-carriers, and 26 controls. In distinguishing LRRK2 -associated PD and iPD, the mean sensitivity was 95.4% (SD 17.8%) and mean specificity was 89.6% (SD 26.5%). Voice features for non-manifesting carriers, related non-carriers, and controls were much less discriminatory. Vocal deficits in LRRK2 -associated PD may be different than those in iPD. These preliminary results warrant longitudinal analyses …and replication in larger cohorts. Show more

Keywords: LRRK2 mutation, Parkinson’s disease, biomarker, voice

DOI: 10.3233/JPD-181389

Citation: Journal of Parkinson's Disease, vol. 8, no. 4, pp. 503-510, 2018

Authors: Gravell, Rhys | Duncan, Gordon W. | Khoo, Tien K. | Burn, David J. | Sayer, Avan A. | Barker, Roger A. | Lawson, Rachael Ashleigh | Yarnall, Alison Jane

Article Type: Short Communication

Abstract: Recent guidance by the National Institute for Health and Care Excellence (NICE) focuses on the management of people with multimorbidity, including Parkinson’s disease (PD). To date there has been little exploration of this in neurodegenerative diseases. This study aimed to explore the associations between multimorbidity, motor severity and quality of life (QoL) in early PD. Regression analyses determined whether multimorbidity was significantly associated with disease severity and QoL. Multimorbidity was a small but significant predictor of QoL in people with incident PD, but not motor severity, suggesting that they may benefit from a tailored multidisciplinary approach to care.

Keywords: Multimorbidity, Parkinson’s disease, quality of life, motor severity

DOI: 10.3233/JPD-181428

Citation: Journal of Parkinson's Disease, vol. 8, no. 4, pp. 511-515, 2018

Authors: Chahine, Lana M. | Beach, Thomas G. | Seedorff, Nicholas | Caspell-Garcia, Chelsea | Coffey, Christopher S. | Brumm, Michael | Adler, Charles H. | Serrano, Geidy E. | Linder, Carly | Mosovsky, Sherri | Foroud, Tatiana | Riss, Holly | Ecklund, Dixie | Seibyl, John | Jennings, Danna | Arnedo, Vanessa | Riley, Lindsey | Dave, K.D. | Mollenhauer, Brit | on behalf of the Systemic sSynuclein Sampling study

Article Type: Research Article

Abstract: Background: α -synuclein is a lead Parkinson’s disease (PD) biomarker. There are conflicting reports regarding accuracy of α -synuclein in different tissues and biofluids as a PD biomarker, and the within-subject anatomical distribution of α -synuclein is not well described. The Systemic Synuclein Sampling Study (S4) aims to address these gaps in knowledge. The S4 is a multicenter, cross-sectional, observational study evaluating α -synuclein in multiple tissues and biofluids in PD and healthy controls (HC). Objective: To describe the baseline characteristics of the S4 cohort and safety and feasibility of this study. Methods: Participants underwent motor …and non-motor clinical assessments, dopamine transporter SPECT, biofluid collection (cerebrospinal fluid, saliva, and blood), and tissue biopsies (skin, sigmoid colon, and submandibular gland). Biopsy adequacy was determined based on presence of adequate target tissue. Tissue sections were stained with the 5C12 monoclonal antibody against unmodified α -synuclein. All specimens were acquired and processed in a standardized manner. Adverse events were systematically recorded. Results: The final cohort consists of 82 participants (61 PD, 21 HC). In 68 subjects (83%), all types of specimens were obtained but only 50 (61%) of subjects had all specimens both collected and evaluable for α -synuclein. Mild adverse events were common, especially for submandibular gland biopsy, but only 1 severe adverse event occurred. Conclusion: Multicenter tissue and biofluid sampling for α -synuclein is feasible and generally safe. S4 will inform understanding of the concurrent distribution of α -synuclein pathology and biomarkers in biofluids and peripheral nervous system in PD. Show more

Keywords: Biomarkers, needle biopsy, Parkinson’s disease, synucleins

DOI: 10.3233/JPD-181434

Citation: Journal of Parkinson's Disease, vol. 8, no. 4, pp. 517-527, 2018

Authors: Bottero, Virginie | Santiago, Jose A. | Potashkin, Judith A.

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) shares pathological and clinical features with progressive supranuclear palsy (PSP) patients making the diagnosis challenging. Distinguishing PD from PSP is crucial given differences in disease course, treatment and clinical management. Objective: Although some progress has been made in the discovery of biomarkers for PD and PSP, there is an urgent need to identify additional biomarkers capable of distinguishing between these diseases. Methods: In this study, we tested the phosphatases DUSP8 and PTPRC for their diagnostic potential using quantitative PCR assays, in blood of 138 samples from participants nested in …the Parkinson’s Disease Biomarkers Program. Results: Relative abundance of PTPRC mRNA was downregulated in PSP patients compared to PD and healthy controls, whereas there was no significant difference in the expression of DUSP8 . Interestingly, PTPRC mRNA correlated with the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total score and MDS-UPDRS- part III, thus indicating it might be useful as part of a biosignature to stratify patients according to disease severity and progression. Conclusions: Collectively, these results suggest that PTPRC expression may be useful for distinguishing PD from PSP patients as part of a biosignature. Evaluation of PTPRC along with additional biomarkers in a larger and well-characterized longitudinal study is warranted. Show more

Keywords: Parkinson’s disease, progressive supranuclear palsy, biomarkers, gene expression, PTPRC, phosphatase

DOI: 10.3233/JPD-181391

Citation: Journal of Parkinson's Disease, vol. 8, no. 4, pp. 529-537, 2018

Authors: Lichter, David Gordon | Benedict, Ralph Holmes Boring | Hershey, Linda Ann

Article Type: Research Article

Abstract: Background: In Parkinson’s disease (PD), postural instability-gait disorder (PIGD) has been associated with more rapid cognitive decline, dementia, and greater non-motor symptom (NMS) burden. Objective: To assess the importance of balance-gait disorder, relative to and in combination with other clinical measures, as a risk factor for cognitive impairment, dementia and NMS burden in PD. Methods: 164 PD subjects were evaluated in a retrospective cross-sectional study using the MDS-UPDRS scale, MMSE and Clinical Dementia Rating Scale. Using univariate comparisons followed by multiple stepwise regression, we identified factors most closely associated with NMS burden and concurrent dementia. Nominal …logistic regression and linear discriminant analysis was used to compute receiver operating characteristic curves and to measure sensitivity and specificity of predictors of dementia. Results: Dementia was more frequent in those with the PIGD phenotype (χ 2  = 11.49, p  = 0.003). The MDS-UPDRS balance-gait measure, excluding freezing of gait, was the single best predictor not only of concurrent cognitive impairment and dementia (F = 37.16, p  < 0.001) but also of NMS burden, predicting 29% of the MDS-UPDRS total non-motor experiences of daily living score (F = 67.14, p  < 0.0001). This measure, together with combined severity of hallucinations/psychosis, daytime sleepiness and urinary problems, a closely correlated symptom cluster (r = 0.63 p  < 0.0001), accurately classified 84% of patients with dementia. Conclusions: In PD, balance-gait impairment is closely associated with dementia and NMS burden, particularly the linked symptoms of cognitive impairment, psychosis, daytime sleepiness and urinary dysfunction. This phenotype characterizes patients likely to require closer surveillance and more comprehensive care. Confirmation of these findings in prospective longitudinal studies might help refine predictive algorithms designed to identify PD patients more likely to progress from mild cognitive impairment to dementia. Show more

Keywords: Parkinson’s disease, mild cognitive impairment, dementia, lewy body, balance, postural, characteristic, receiver operating, predictive value of tests

DOI: 10.3233/JPD-181375

Citation: Journal of Parkinson's Disease, vol. 8, no. 4, pp. 539-552, 2018

Authors: Fereshtehnejad, Seyed-Mohammad | Lökk, Johan | Wimo, Anders | Eriksdotter, Maria

Article Type: Research Article

Abstract: Background: Whether dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) are distinct disorders or two subtypes of the same entity, is not yet fully understood. There is a dearth of knowledge on differences in longitudinal clinical outcomes between DLB and PDD. Objective: We aimed to compare longitudinal trend of cognitive decline, mortality, and their determinant factors between patients with DLB and PDD. Methods: At baseline, we recruited 1110 DLB, and 764 PDD patients registered in the Swedish dementia registry (SveDem) during 2007–2015. Cognitive status was assessed at baseline and each follow-up visit by mini-mental …state examination (MMSE). At least one follow-up MMSE was available for 411 (37.0%) DLB and 229 (30.0%) PDD patients. Rate of cognitive decline and mortality risk were compared between the two groups. Results: After an average of 2-years, the rate of cognitive decline did not differ between DLB (1.1 MMSE unit/year ) and PDD (1.2 MMSE unit/year ) groups (p  = 0.970). There was no significant difference in the median survival time between DLB (4.0 years) and PDD (4.1 years) groups (Log rank p  = 0.614). Antipsychotic drug use in DLB and larger number of medications in PDD were the most important determinants of faster annual cognitive decline. Conclusions: Our findings from real-world clinical practice demonstrated that the rate of cognitive decline and mortality do not differ significantly between DLB and PDD at least over 2 years, yet, various factors might determine clinical outcome in these two groups. It seems that DLB and PDD are probably similar synucleinopathies, with phenotypical variations in the order of manifestations rather than course of progression and clinical outcome. Show more

Keywords: Parkinson’s disease dementia, dementia with lewy bodies, cognitive decline, mortality

DOI: 10.3233/JPD-181367

Citation: Journal of Parkinson's Disease, vol. 8, no. 4, pp. 553-561, 2018