Journal of Parkinson's Disease - Volume 5, issue 3

Authors: Simon-Tov, Shlomi | Dinur, Tama | Giladi, Nir | Bar-Shira, Anat | Zelis, Mayaan | Zimran, Ari | Elstein, Deborah

Article Type: Research Article

Abstract: Background: Poor color discrimination among patients with Parkinson disease (PD) has long been recognized. It has been shown that carrying one or two mutations in the β-glucocerebrosidase gene (GBA) for the autosomal disease Gaucher disease (GD), as based initially on clinical evidence, is a genetic risk factor for early-onset PD. Objective: The purpose of this study was to assess color discrimination in patients with one or two GBA mutations relative to healthy controls to ascertain whether this function is affected when persons with GD or even one GBA mutation develop PD. Methods: …The Farnsworth-Munsell 100 hue test (FMHT) was evaluated among patients with GD+PD compared to patients with GD only, obligate GBA carriers with and without PD, patients with PD only, and healthy controls. FMHT outcome include computer-generated TES (Total Error Score) and values recommended by Vingrys & King-Smith. Results: Six groups of 10 persons were tested. Significant differences were seen for male GD+PD and for age in PD. The highest mean TES was in the PD only group, the lowest in the GD only group. There was a significant difference because of PD in groups with GD and GBA carriers. GD+PD means were between GD only and PD only mean scores. Conclusions: These findings confirm that PD impacts color discrimination, more in males with GD+PD but nonetheless, GD+PD patients (but not GBA carriers) had better scores than PD only patients. Show more

DOI: 10.3233/JPD-150585

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 525-531, 2015

Authors: Matthews, Helen | Stamford, Jon | Saha, Romi | Martin, Anne

Article Type: Research Article

Abstract: Background: The negative impact of wearing-off on the quality of life (QoL) of people with Parkinson’s (PWPs) is well established. However, most studies have been performed from the clinician’s perspective, and the needs of PwPs and care partners have been considered separately. Objective: This survey aimed to better understand the impact of wearing-off on both patient and care partner lives and to assess how often they are asked about their QoL in their specialist consultations. Methods: PwPs and care partners registered with The Cure Parkinson’s Trust database were invited to participate in …an online survey consisting of 21 questions about wearing-off and QoL. Data was collected for matched pairs (PwP and their care partner). Results: 47 matched pairs completed the survey. The five symptoms most commonly reported as troublesome were: tiredness, slowness, reduced dexterity, slowness of movement and slowness in the early morning. Overall, 47% of PwPs indicated that they discuss their QoL at all/most appointments. Whereas most PwPs and their care partners (87% and 74% , respectively) said that they understood what ‘wearing-off’ means, only 30% of PwPs and 17% of care partners gave a correct answer on further questioning. There was no evidence to support the idea that care partners notice the signs of wearing-off before the PwP. Conclusions: This matched survey underscores the broad impact that Parkinson’s has on daily life on both PwPs and their care partners, and indicates the need for improved communication between PwPs, care partners and their physicians. Show more

Keywords: Quality of life, care partner, wearing-off, Parkinson’s disease

DOI: 10.3233/JPD-150547

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 533-539, 2015

Authors: Alvarado-Bolaños, Alonso | Cervantes-Arriaga, Amin | Rodríguez-Violante, Mayela | Llorens-Arenas, Rodrigo | Calderón-Fajardo, Humberto | Millán-Cepeda, Roxanna | Leal-Ortega, Roberto | Estrada-Bellmann, Ingrid | Zuñiga-Ramírez, Carlos

Article Type: Research Article

Abstract: Background: Neuropsychiatric symptoms in Parkinson’s disease (PD) are frequent. Impact of neuropsychiatric symptoms on quality of life has recently become a relevant topic of research due to its potential to develop targeted therapies to improve quality of life. Objective: To determine the impact of neuropsychiatric symptoms in patients with PD using the Parkinson’s DiseaseQuestionnaire Short Form (PDQ-8). Methods: Consecutive patients with PD were evaluated with the Scale for Evaluation of Neuropsychiatric Disorders in Parkinson’s disease (SEND-PD) and PDQ-8 scales separately. Association between neuropsychiatric symptoms and quality of life was explored using, means …comparisons, correlation coefficients and multiple regression models. Results: A total of 492 patients were included for the study. Overall, 44.5% had psychotic symptoms, 76.5% had alterations on mood/apathy domains, and 27% had an impulse control disorder. All neuropsychiatric symptoms had an effect on the PDQ-8 with a moderate to large effect size. Correlation coefficients ranged from 0.17 to 0.63 between neuropsychiatric symptoms and quality of life (p  <  0.001, in all cases). The regression model showed that mood/apathy alterations and impulse control disorders, along with MDS-UPDRS III accounted for 49.8% of variance in the PDQ-8 simplified index (F = 122.98; p  <  0.001). Mood/apathy alterations showed the highest correlation coefficient (0.63, p  <  0.001) and β (0.53, p  <  0.001). Conclusions: Both the presence and severity of neuropsychiatric symptoms, in particular mood/apathy alterations,had a significant impact on quality of life in subjects with PD. Show more

Keywords: Parkinson’s disease, depression, apathy, impulse control disorders, psychosis, quality of life

DOI: 10.3233/JPD-150597

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 541-548, 2015

Authors: Hayes, Heather A. | Hunsaker, Nikelle | Dibble, Leland E.

Article Type: Research Article

Abstract: Background: Deficits in implicit motor sequence learning (IMSL) in individuals with Parkinson disease (PD) compared to age matched healthy controls (HC) are unclear. Objective: The purpose of this paper is to present results of a systematic review with a meta-analysis examining the hypothesis that IMSL is impaired in individuals with PD when compared to HC. Methods: Fifteen articles met our final criteria and assessed 299 individuals with PD and 244 HC. Raw mean and standard deviation data for the final block of repeated and final block of random practice trials were obtained …to calculate sequence-specific learning (SSL) for individuals with PD and HC. Forest plots were used to depict the comparison of the groups by assessing standardized mean difference with random effect size. Results: A significant and moderate effect size, 0.83 was found suggesting that individuals with PD demonstrated impaired SSL of motor sequences compared to HC. Conclusions: Individuals with PD demonstrate a deficit compared with HC in their ability to implicitly learn motor tasks. Existing research lacks detail on the factors which may alter IMSL, either negatively or positively, such as the design features of current IMSL paradigms utilized and disease-specific characteristics. Successful motor rehabilitation of functional tasks in persons with PD is highly dependent on IMSL; therefore, an improved knowledge of the influence of these additional variables is critical. Show more

Keywords: Implicit motor sequence learning, Parkinson disease

DOI: 10.3233/JPD-140441

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 549-560, 2015

Authors: Reimão, Sofia | Pita Lobo, Patrícia | Neutel, Dulce | Guedes, Leonor Correia | Coelho, Miguel | Rosa, Mario M. | Ferreira, Joana | Abreu, Daisy | Gonçalves, Nilza | Morgado, Carlos | Nunes, Rita G. | Campos, Jorge | Ferreira, Joaquim J.

Article Type: Research Article

Abstract: Background: Specific MR sequences have been able to identify the loss of neuromelanin in the substantia nigra (SN) of early stage Parkinson’s disease (PD) patients. Since this technique may have a significant impact in clinical patient management, easy and widely available imaging analysis is needed for routine use. Objective: In this study we compared a quantitative analysis with a visual assessment of SN neuromelanin-sensitive MR images in early stage PD patients, in terms of pattern changes recognition and diagnostic accuracy. Methods: The inclusion criteria were untreated “de novo” PD patients or a …2–5 year PD duration; in addition, age matched controls were enrolled. These were studied with a high-resolution T1-weighted MR imaging sequence at 3.0 Tesla to visualize neuromelanin. The primary outcome was the comparison of quantitative width measurement with visual assessment by experienced neuroradiologists of SN neuromelanin sensitive MR images for PD diagnosis. Results: A total of 12 “de novo” PD patients, 10 PD patients with 2–5 year disease duration and 10 healthy controls were evaluated. We obtained a good accuracy in discriminating early-stage PD patients from controls using either a quantitative width measurement of the T1 high signal or a simple visual image inspection of the SN region. Conclusions: Visual inspection of neuromelanin-sensitive MR images by experienced neuroradiologists provides comparable results to quantitative width measurement in the detection of early stage PD SN changes and may become a useful tool inclinical practice. Show more

Keywords: Neuromelanin, locus ceruleus, substantia nigra, Parkinson’s disease, MRI

DOI: 10.3233/JPD-150551

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 561-567, 2015

Authors: Tard, Céline | Demailly, Franck | Delval, Arnaud | Semah, Franck | Defebvre, Luc | Dujardin, Kathy | Moreau, Caroline

Article Type: Research Article

Abstract: Background: Brain metabolic profiles of patients with Parkinson’s disease (PD) and cognitive impairment or dementia are now available. It would be useful if data on brain metabolism were also predictive of the risk of a pejorative cognitiveevolution - especially in the multidisciplinary management of advanced PD patients. Objective: The primary objective was to determine whether a specific brain metabolic pattern is associated with cognitive decline in PD. Methods: Sixteen advanced PD patients were screened for the absence of cognitive impairment (according to the Mattis dementia rating scale, MDRS) and underwent [18 F]-fluorodeoxyglucose …positron emission tomography brain imaging in the “off drug” state. The MDRS was scored again about two years later, categorizing patients as having significant cognitive decline (decliners) or not (stables). The two groups were then compared in terms of their brain metabolism at inclusion. Results: There were six decliners and ten stables. Significant hypometabolism in the two precunei (Brodmann area (BA) 31), the left middle temporal gyrus (BA21) and the left fusiform gyrus (BA37) was found in the decliner group compared withthe stables. Conclusion: In advanced PD, a particular metabolic pattern may be associated with the onset of significant cognitive decline. Show more

DOI: 10.3233/JPD-150583

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 569-574, 2015

Authors: Canoy, Marcel | Faber, Marjan J. | Munneke, Marten | Oortwijn, Wija | Nijkrake, Maarten J. | Bloem, Bastiaan R.

Article Type: Research Article

Abstract: In the Netherlands, the largest health technology assessment (HTA) program funds mainly (cost-)effectiveness studies and implementation research. The cost-effectiveness studies are usually controlled clinical trials which simultaneously collect cost data. The success of a clinical trial typically depends on the effect size for the primary outcome, such as health gains or mortality rates. A drawback is that in case of a negative primary outcome, relevant other (and perhaps more implicit) benefits might be missed. Conversely, positive trials can contain adverse outcomes that may also remain hidden. The capability approach (developed by Nobel Prize winner and philosopher Sen) is an instrument …that may reveal such “hidden treasures and secret pitfalls” that lie embedded within clinical trials, beyond the more traditional outcomes. Here, we exemplify the possible merits of the capability approach using a large clinical trial (funded by the HTA program in the Netherlands) that aimed to evaluate the ParkinsonNet concept, an innovative network approach for Parkinson patients. This trial showed no effects for the primary outcome, but the ParkinsonNet concept tested in this study was nevertheless met with great enthusiasm and was rapidly implemented throughout an entire country, and meanwhile also internationally. We applied the capability approach to the ParkinsonNet concept, and this analysis yielded additional benefits within several capability domains. These findings seems to substantiate the claim that richer policy debates may ensue by applying the capability approach to clinical trial data, in addition to traditional outcomes. Show more

Keywords: Cost-benefit analysis, value-based purchasing, outcome assessment, organizational innovation, patient-centered care

DOI: 10.3233/JPD-150612

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 575-580, 2015

Authors: Stephenson, Diane | Hu, Michele T. | Romero, Klaus | Breen, Kieran | Burn, David | Ben-Shlomo, Yoav | Bhattaram, Atul | Isaac, Maria | Venuto, Charles | Kubota, Ken | Little, Max A. | Friend, Stephen | Lovestone, Simon | Morris, Huw R. | Grosset, Donald | Sutherland, Margaret | Gallacher, John | Williams-Gray, Caroline | Bain, Lisa J. | Avilés, Enrique | Marek, Ken | Toga, Arthur W. | Stark, Yafit | Forrest Gordon, Mark | Ford, Steve

Article Type: Research Article

Abstract: Parkinson’s disease is a complex heterogeneous disorder with urgent need for disease-modifying therapies. Progress in successful therapeutic approaches for PD will require an unprecedented level of collaboration. At a workshop hosted by Parkinson’s UK and co-organized by Critical Path Institute’s (C-Path) Coalition Against Major Diseases (CAMD) Consortiums, investigators from industry, academia, government and regulatory agencies agreed on the need for sharing of data to enable future success. Government agencies included EMA, FDA, NINDS/NIH and IMI (Innovative Medicines Initiative). Emerging discoveries in new biomarkers and genetic endophenotypes are contributing to our understanding of the underlying pathophysiology of PD. In parallel there …is growing recognition that early intervention will be key for successful treatments aimed at disease modification. At present, there is a lack of a comprehensive understanding of disease progression and the many factors that contribute to disease progression heterogeneity. Novel therapeutic targets and trial designs that incorporate existing and new biomarkers to evaluate drug effects independently and in combination are required. The integration of robust clinical data sets is viewed as a powerful approach to hasten medical discovery and therapies, as is being realized across diverse disease conditions employing big data analytics for healthcare. The application of lessons learned from parallel efforts is critical to identify barriers and enable a viable path forward. A roadmap is presented for a regulatory, academic, industry and advocacy driven integrated initiative that aims to facilitate and streamline new drug trials and registrations in Parkinson’s disease. Show more

Keywords: Data standards, privacy, data integration, collaboration, quantitative disease progression, regulatory science

DOI: 10.3233/JPD-150570

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 581-594, 2015

Authors: Brehm, Nadine | Rau, Katrin | Kurz, Alexander | Gispert, Suzana | Auburger, Georg

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is characterized by loss of midbrain dopaminergic neurons, which are affected by cytoplasmic inclusions, named Lewy pathology. The main component is alpha-synuclein (SNCA), a protein modulating SNARE-complex dependent neurotransmission. SNCA mutations trigger dominantly inherited PD variants and sporadic cases of PD via aggregation and transmission. SNCA and isoforms of the 14-3-3 family show sequence homology, protein interaction and joint aggregation, so 14-3-3 s may be key molecules of pathogenesis. Objective: We aimed to identify the relevant isoforms in midbrain and to distinguish for the first time the changes that occur very early …versus those that progress with pathology. Methods: We assessed expression of the 14-3-3 family with quantitative RT-PCR and immunoblots of differential solubility fractions in mice with A53T-SNCA overexpression longitudinally at different ages. Results: Transcript levels showed reductions at age 3 months with increases at later ages for the beta, eta and zeta isoforms. Protein levels at age 3 months exhibited a concordant reduction only for beta, while increased insolubility was observed for epsilon and zeta. At age 18 months only the reduction of 14-3-3 beta protein remained significant. Thus, the toxic gain-of-function of alpha-synuclein leads to early transitory alterations of several 14-3-3 isoforms. When the levels of soluble 14-3-3 proteins become apparently normal during later life, increasing amounts of beta, eta and zeta mRNA are produced, possibly to compensate for protein insolubility and aggregation in a SNCA/14-3-3 complex. Conclusions: These data may contribute to identify key molecular events that reflect Parkinson’s disease risk and progression. Show more

Keywords: Lewy body disease, gene expression profiles, signal transduction, biomarkers

DOI: 10.3233/JPD-150606

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 595-604, 2015

Authors: Kim, Young Eun | Kang, Suk Yun | Ma, Hyeo-Il | Ju, Young-Su | Kim, Yun Joong

Article Type: Research Article

Abstract: Background: Although the hummingbird sign (HBS) is a distinctive feature of progressive supranuclear palsy (PSP) VS. idiopathic Parkinson’s disease (IPD) and other parkinsonian disorders, there are no consensus criteria for its identification. Objective: To develop consensus criteria for the HBS to enable accurate communication between researchers and physicians, we developed a new radiologic rating scale for the HBS (the HBS-RS), and the inter-rater reliability (IRR) and diagnostic validity of the HBS-RS were evaluated. Methods: Two raters blinded to the clinical diagnoses reviewed T1 midsagittal magnetic resonance images of 133 patients with IPD …(n  = 93) or PSP (n  = 40). The existence of the HBS was assessed in two steps that were separated by two weeks; the first was based on their own experience and the second was according to the HBS-RS. The HBS-RS comprises 4 items (contour of the third ventricle floor, shape of the beak, shape of the hummingbird head, and midbrain atrophy), with weighted scores from 0 to 2. Results: The IRR of individual items in the HBS-RS and of the composite scores showed moderate-to-good agreement (Cohen’s kappa [κ ], 0.479–0.766) and were observed to be highest for the contour of the third ventricle floor. The sensitivities and specificities varied depending on the cut-off for each item or for the composite scores. The sensitivities for each item were high (85.0–92.5) at a low cut-off (0 VS. 1 or 2). The specificities reached more than 80% when the composite scores of the HBS-RS were used. Receiver operating characteristic curves for the total HBS-RS scores showed fair diagnostic accuracy for PSP (AUC, 0.76 and 0.73). Conclusions: The HBS-RS is a simple and measurable visual assessment tool to identify the HBS, with adjustable diagnostic validity for PSP. The results suggest that the HBS-RS may be used for objective measurements of the HBS in research and in the clinic. Show more

Keywords: Progressive supranuclear palsy, idiopathic Parkinson’s disease, hummingbird sign, magnetic resonance imaging, inter-rater reliability

DOI: 10.3233/JPD-150537

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 605-612, 2015