Journal of Parkinson's Disease - Volume 7, issue 4

Authors: Carroll, Camille B. | Wyse, Richard K.H.

Article Type: Review Article

Abstract: Many now believe the holy grail for the next stage of therapeutic advance surrounds the development of disease-modifying approaches aimed at intercepting the year-on-year neurodegenerative decline experienced by most patients with Parkinson’s disease (PD). Based on recommendations of an international committee of experts who are currently bringing multiple, potentially disease-modifying, PD therapeutics into long-term neuroprotective PD trials, a clinical trial involving 198 patients is underway to determine whether Simvastatin provides protection against chronic neurodegeneration. Statins are widely used to reduce cardiovascular risk, and act as competitive inhibitors of HMG-CoA reductase. It is also known that statins serve as ligands …for PPARα, a known arbiter for mitochondrial size and number. Statins possess multiple cholesterol-independent biochemical mechanisms of action, many of which offer neuroprotective potential (suppression of proinflammatory molecules & microglial activation, stimulation of endothelial nitric oxide synthase, inhibition of oxidative stress, attenuation of α-synuclein aggregation, modulation of adaptive immunity, and increased expression of neurotrophic factors). We describe the biochemical, physiological and pharmaceutical credentials that continue to underpin the rationale for taking Simvastatin into a disease-modifying trial in PD patients. While unrelated to the Simvastatin trial (because this conducted in patients who already have PD), we discuss conflicting epidemiological studies which variously suggest that statin use for cardiovascular prophylaxis may increase or decrease risk of developing PD. Finally, since so few disease-modifying PD trials have ever been launched (compared to those of symptomatic therapies), we discuss the rationale of the trial structure we have adopted, decisions made, and lessons learnt so far. Show more

Keywords: Parkinson’s disease, Simvastatin, disease modification, clinical trial

DOI: 10.3233/JPD-171203

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 545-568, 2017

Authors: Tofaris, George K.

Article Type: Review Article

Abstract: Extracellular vesicles including exosomes are released by a variety of cell types including neurons and exhibit molecular profiles that reflect normal and disease states. As their content represents a snapshot of the intracellular milieu, they could be exploited as biomarkers of the otherwise inaccessible brain microenvironment. In addition they may contribute to the progression of neurodegenerative disorders by facilitating the spread of misfolded proteins at distant sites or activating immune cells. This review summarizes recent advances in the study of exosomes in Parkinson’s disease pathophysiology and their potential as disease biomarkers.

Keywords: Aggregation, alpha-synuclein, biomarker, exosome, LRRK2, neurodegeneration

DOI: 10.3233/JPD-171176

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 569-576, 2017

Authors: Thirtamara-Rajamani, Keerthi | Li, Peipei | Escobar Galvis, Martha L. | Labrie, Viviane | Brundin, Patrik | Brundin, Lena

Article Type: Review Article

Abstract:  Several large genome wide association studies have identified a locus in close proximity to the gene encoding the enzyme aminocarboxymuconate-semialdehyde-decarboxylase (ACMSD) to be associated with the risk for Parkinson’s disease (PD), tentatively suggesting that this enzyme might influence PD pathogenesis. Further support for this comes from the recent identification of a disease-segregating stop codon mutation in ACMSD in a family with Parkinsonism, and a missense mutation in the ACMSD gene predicted to disrupt enzyme function in an individual with typical PD. ACMSD is part of the kynurenine pathway, responsible for the catalytic breakdown of tryptophan into NAD+ , …generating several neuroactive metabolites in the process. The enzyme is located at a key branch-point of the pathway, limiting the production of the neurotoxin quinolinic acid, which has excitotoxic and inflammatory properties. In this review, we discuss the genetic findings in light of the functions of ACMSD and its potential involvement in PD pathogenesis. Show more

Keywords: ACMSD, kynurenine pathway, Parkinson’s disease, oxidative stress, excitotoxicity, neuroinflammation

DOI: 10.3233/JPD-171240

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 577-587, 2017

Authors: Brahmachari, Saurav | Karuppagounder, Senthilkumar S. | Ge, Preston | Lee, Saebom | Dawson, Valina L. | Dawson, Ted M. | Ko, Han Seok

Article Type: Review Article

Abstract:  Although the etiology of Parkinson’s disease (PD) is poorly understood, oxidative stress has long been implicated in the pathogenesis of the disease. However, multifaceted and divergent signaling cascades downstream of oxidative stress have posed challenges for researchers to identify a central component of the oxidative stress-induced pathways causing neurodegeneration in PD. Since 2010, c-Abl—a non-receptor tyrosine kinase and an indicator of oxidative stress—has shown remarkable potential as a future promising drug target in PD therapeutics. Although, the constitutively active form of c-Abl, Bcr-Abl, has a long history in chronic myeloid leukemia and acute lymphocytic leukemia, the role of c-Abl in …PD and relevant neurodegenerative diseases was completely unknown. Recently, others and we have identified and validated c-Abl as an important pathogenic mediator of the disease, where activated c-Abl emerges as a common link to various PD-related inducers of oxidative stress relevant to both sporadic and familial forms of PD and α -synucleinopathies. This review discusses the role of c-Abl in PD and the latest advancement on c-Abl as a drug target and as a prospective biomarker. Show more

Keywords: Alpha-synuclein, biomarkers, c-Abl, c-Abl inhibitors, oxidative stress, parkin, Parkinson’s disease

DOI: 10.3233/JPD-171191

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 589-601, 2017

Authors: Bacchi, Stephen | Chim, Ivana | Kramer, Philippe | Postuma, Ronald B.

Article Type: Research Article

Abstract: Background: Domperidone is a proposed treatment of orthostatic hypotension (OH) in Parkinson’s disease (PD). However, domperidone use in PD is tempered by concerns regarding QT prolongation and ventricular tachyarrhythmia and sudden cardiac death (VT/SCD). Objective: The aim is to identify peer-reviewed studies in which either (1) the effect of domperidone on blood pressure in patients with PD, or (2) the adverse effects associated with domperidone use in PD patients has been reported. Methods: PubMed, EMBASE, Medline and Scopus were searched using the terms Parkinson ’s disease and domperidone . Results: Twenty-two articles fulfilled …the inclusion criteria. One study was a randomized placebo-controlled trial with domperidone administration independent of the commencement of dopaminergic medications. This study identified a non-statistically significant trend that domperidone may be beneficial for OH in PD. Several studies identified statistically significant differences in BP with domperidone in the setting of initiating dopaminergic medication. There is currently the most evidence to support domperidone use with apomorphine commencement. Studies reporting domperidone adverse effects in PD patients were largely retrospective or cross-sectional. The identified studies demonstrated that domperidone may cause QT prolongation and is associated with increased risk of VT/SCD in PD patients with preexisting cardiac disease. Conclusions: Domperidone may help to ameliorate OH associated with dopaminergic medications in PD, namely when used in conjunction with apomorphine. When considering whether to use domperidone in PD, factors that should be taken into account include pre-existing heart disease and drug interactions, as well as the impact of OH on mobility, cognition and quality of life. Show more

Keywords: Apomorphine, domperidone, orthostatic hypotension, sudden cardiac death

DOI: 10.3233/JPD-171209

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 603-617, 2017

Authors: Andréasson, Mattias | Brodin, Lovisa | Laffita-Mesa, José Miguel | Svenningsson, Per

Article Type: Research Article

Abstract: Background: Polyneuropathy (pnp) is recognized as a clinical feature of Parkinson’s disease (PD). Whether pnp is a result of the alpha-synucleinopathy or related to treatment is debated. Previous studies support underlying disturbances in the methionine cycle mediated by L-dopa. Objective: Describe possible relationships between methionine cycle metabolism and the development of pnp in L-dopa treated PD. Furthermore, we aim to investigate possible genetic risk factors by genotyping specific SNPs in enzymes involved in the abovementioned pathways. Methods: In a cross-sectional study design, L-dopa treated PD patients (n  = 33) and controls (n  = 16) were evaluated with biochemical …and genetic analyses. Subjects were assessed clinically and with regards to signs of pnp using established clinical neuropathy rating scales. Results: 16/33 patients fulfilled a study diagnosis of pnp compared to 0 age-matched controls. Levels of homocysteine (Hcy) were significantly higher in patients with pnp (n  = 16) compared to controls. A significant correlation between neuropathy scores and Hcy was seen in the whole patient group (n  = 33). A significant difference in the genotype distribution of the COMT A158G polymorphism was demonstrated, favoring the low activity genotype in patients with pnp compared to both controls and patients without pnp. Conclusions: Pnp is a prevalent condition in L-dopa treated PD and an association may exist with elevated levels of Hcy, possibly reflecting an underlying impaired cellular methylation capacity. Furthermore, an association may exist between the low activity COMT genotype and pnp. These preliminary findings and the suggested pathophysiological mechanisms should be confirmed in future large-scale studies. Show more

Keywords: Parkinson’s disease, peripheral neuropathies, homocysteine, COMT, vitamin B12, levodopa

DOI: 10.3233/JPD-171127

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 619-628, 2017

Authors: Cattaneo, Carlo | Müller, Thomas | Bonizzoni, Erminio | Lazzeri, Gabriele | Kottakis, Ioannis | Keywood, Charlotte

Article Type: Research Article

Abstract: Background: Mood disorders are very frequent in Parkinson’s Disease (PD), and their effective treatment is still a major unresolved issue: growing evidence suggests that glutamatergic system dysfunction is directly involved. Safinamide is a drug with an innovative mechanism of action, dopaminergic and non-dopaminergic, that includes the reversible inhibition of the monoamine oxidase-B (MAO-B) enzyme and the modulation of excessive glutamate release through the use- and state-dependent blockade of the sodium channels. Objective: To investigate the effects of safinamide on mood over two-year treatment in PD patients with motor fluctuations. Methods: This was a post-hoc analysis …of the data from studies 016 and 018. The analysis focused on outcomes related to mood, namely: scores of the “Emotional well-being” domain of the Parkinson’s Disease Questionnaire (PDQ-39), scores of the GRID Hamilton Rating Scale for Depression (GRID-HAMD) and the proportion of patients reporting depression as an adverse event over the entire treatment period. Results: Safinamide, compared to placebo, significantly improved the PDQ-39 “Emotional well-being” domain after6-months (p  = 0.0067) and 2 years (p  = 0.0006), as well as the GRID-HAMD (p  = 0.0408 after 6 months and p  = 0.0027 after 2 years). Significantly fewer patients in the safinamide group, compared to placebo, experienced depression as adverse event (p  = 0.0444 after 6 months and p  = 0.0057 after 2 years). Conclusion: The favorable effect of safinamide on mood may be explained by the improvement in wearing off and by its modulation of glutamatergic hyperactivity and reversible MAO-B inhibition. Prospective studies are warranted to investigate this potential benefit. Show more

Keywords: Glutamate, mood, Parkinson’s disease, safinamide

DOI: 10.3233/JPD-171143

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 629-634, 2017

Authors: Lythe, Vanessa | Athauda, Dilan | Foley, Jennifer | Mencacci, Niccolò E. | Jahanshahi, Marjan | Cipolotti, Lisa | Hyam, Jonathan | Zrinzo, Ludvic | Hariz, Marwan | Hardy, John | Limousin, Patricia | Foltynie, Tom

Article Type: Research Article

Abstract: Background: Recent evidence suggests that glucosidase beta acid (GBA) mutations predispose Parkinson’s disease (PD) patients to a greater burden of cognitive impairment and non-motor symptoms. This emerging knowledge has not yet been considered in patients who have undergone deep brain stimulation (DBS); a surgery that is generally contraindicated in those with cognitive deficits. Objective: To explore the long-term phenotypic progression of GBA- associated PD, in a DBS cohort. Methods: Thirty-four PD patients who had undergone DBS surgery between 2002 and 2011 were included in this study; 17 patients with GBA mutations were matched to …17 non-carriers. Clinical evaluation involved the administration of four assessments: The Mattis Dementia Rating Scale was used to assess cognitive function; non-motor symptoms were assessed using the Non-Motor Symptom Assessment Scale for PD; quality of life was measured using the Parkinson’s Disease Questionnaire; and motor symptoms were evaluated using part III of the Movement Disorders Society Unified Parkinson’s Disease Rating Scale, in on-medication/on-stimulation conditions. Levodopa equivalent doses (LED) and DBS settings were compared with clinical outcomes. Results: At a mean follow-up of 7.5 years after DBS, cognitive impairment was more prevalent (70% vs 19%) and more severe in GBA mutation carriers compared to non-carriers (60% vs 6% were severely impaired). Non-motor symptoms were also more severe and quality of life more impaired in GBA- associated PD. Motor symptoms, LED, and stimulation settings were not significantly different between groups at follow-up. Conclusions: GBA status appears to be an important predictor for non-motor symptom disease progression, after deep brain stimulation surgery. Show more

Keywords: Deep brain stimulation, glucosidase beta acid, Parkinson’s disease, phenotype

DOI: 10.3233/JPD-171172

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 635-644, 2017

Authors: Knudsen, Karoline | Hartmann, Bolette | Fedorova, Tatyana D. | Østergaard, Karen | Krogh, Klaus | Møller, Niels | Holst, Jens J. | Borghammer, Per

Article Type: Research Article

Abstract: Background and objectives: Parkinson’s disease (PD) patients experience several non-motor symptoms from the gastrointestinal tract that may partly be caused by parasympathetic deficiency. The pancreas is densely innervated by the vagus nerve, which mediates early meal-induced secretion of pancreatic polypeptide (PP). Early secretion after sham feeding has been validated as a marker of vagal integrity. Thus, the aim was to evaluate the ratio of increased PP plasma levels after sham feeding in PD and correlate findings with gastrointestinal transit time (GITT). Methods: Twenty-five PD patients and 17 controls were included. PP, insulin, and blood glucose levels were measured …before, during, and after sham feeding with white bread and chocolate spread. GITT was measured using radiopaque markers. Furthermore, faeces samples were analyzed for pancreatic elastase enzyme as a marker of exocrine pancreatic function. Results: PD patients showed significantly lower PP ratio levels after sham feeding, which was most pronounced at 10 minutes. No significant association was seen between attenuated PP response and GITT in PD patients. No between-group differences were seen in glucose or insulin levels over time, but PD patients showed generally lower insulin levels compared to controls. No difference was found in faeces pancreatic elastase. Conclusions: Early-to-moderate stage PD patients demonstrated significantly decreased PP response after sham feeding suggestive of vagal denervation. Show more

Keywords: Pancreatic polypeptide, parasympathetic, Parkinson’s disease, sham feeding, vagus

DOI: 10.3233/JPD-171189

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 645-652, 2017

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

Article Type: Research Article

Abstract: Background: Substantial progress has been made in the discovery of blood biomarkers for Parkinson’s disease (PD), a progressive neurodegenerative disease that affects more than 4 million worldwide. Olfactory dysfunction and dopamine deficits usually precede motor symptoms years before the onset of PD. A readily accessible biomarker useful for identifying patients at risk of PD is expected to accelerate clinical trials. Objective: To evaluate previously identified PD blood RNA biomarkers in a cohort of asymptomatic individuals at risk of PD. Methods: Here we tested 16 previously identified PD RNA biomarkers using quantitative PCR assays in a total …of 269 blood samples at baseline from hyposmic and normosmic participants enrolled in the Parkinson’s Associated Risk Syndrome study. Results: Expression levels of four biomarkers, SOD2 , PKM2 , ZNF134, and ZNF160 were negatively correlated with the total Unified Parkinson’s Disease Rating Scale, thus suggesting these biomarkers may be useful to stratify patients prior to the onset of motor symptoms. Levels of SOD2 were upregulated in hyposmic males compared to females, whereas levels of PKM2 were upregulated in hyposmic males compared to normosmic males and hyposmic females. Further, levels of SOD2 were upregulated in males with abnormal dopamine transporter (DAT) scans compared to females with abnormal DAT scans. Conclusions: These results suggest that some of these biomarkers may be useful for stratification of individuals at risk for PD and that there may be sex differences in the expression of some biomarkers. Future studies in larger longitudinal studies will be key to assessing the validity of these findings. Show more

Keywords: Biomarkers, blood, hyposmia, Parkinson’s disease, PARS, dopamine transporter scans

DOI: 10.3233/JPD-171155

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 653-660, 2017

Authors: Deck, Benjamin L. | Rick, Jacqueline | Xie, Sharon X. | Chen-Plotkin, Alice | Duda, John E. | Morley, James F. | Chahine, Lana M. | Dahodwala, Nabila | Trojanowski, John Q. | Weintraub, Daniel

Article Type: Short Communication

Abstract: Background: The relationship between statins and cognition in Parkinson’s disease (PD) is poorly understood. Objectives: Analyses were performed to determine associations between statin use and cross-sectional and longitudinal cognitive performance in PD. Methods: Neuropsychological tests, medication logs, and ratings of functional abilities were collected from 313 PD participants longitudinally. Results: At baseline, statin users (SU; N = 129) were older, more likely male, and had shorter PD duration than non-statin users (NSU; N = 184). In Cross-sectional analysis, SU performed better on global cognition, Trails B, semantic fluency, and phonemic fluency tasks. Rate of long-term global cognitive (Dementia …Rating Scale-2 and MoCA) decline was significantly less in SU. Show more

Keywords: Apolipoprotein A-I, cognition, hydroxymethylglutaryl-CoA reductase inhibitors, longitudinal studies, Parkinson’s disease, reactive oxygen species

DOI: 10.3233/JPD-171113

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 661-667, 2017

Authors: Sleeman, Isobel | Aspray, Terry | Lawson, Rachael | Coleman, Shirley | Duncan, Gordon | Khoo, Tien K. | Schoenmakers, Inez | Rochester, Lynn | Burn, David | Yarnall, Alison

Article Type: Research Article

Abstract: Background: Previous cross-sectional studies have shown that Parkinson’s disease (PD) patients have lower serum 25-hydroxy vitamin D (25(OH)D) concentrations than controls. Vitamin D deficiency was associated with increased disease severity and cognitive impairment in prevalent PD patients. Objective: The aim of the study was to determine 25(OH)D in newly diagnosed PD and age-matched controls and to assess if there was an association with clinical outcomes (disease severity, cognition and falls) over the 36-month follow up period. Methods: A prospective observational study of newly diagnosed PD patients in the North East of England with age-matched controls (PD, …n  = 145; control, n  = 94). Serum 25(OH)D was assessed at baseline and 18 months. Participants underwent clinical assessment at baseline, 18 and 36 months. One hundred and ten participants with PD also took part in a prospective falls study. Results: Mean serum 25(OH)D concentrations were lower in PD than control participants at baseline (44.1±21.7 vs. 52.2±22.1 nmol/L, p  < 0.05) and 18 months (44.2±23.6 vs. 55.7±28.8 nmol/L, p  < 0.05). Baseline serum 25(OH)D concentration, age, motor score and dosage of dopaminergic medication were significant predictors of variance of motor severity at 36 months ((Δ R2  = 0.039, F = 6.6, p  < 0.01). Serum 25(OH)D was not associated with cognition or falls during the follow up period. Conclusions: Patients with incident PD had significantly lower serum 25(OH)D concentrations than age-matched controls, which may have implications in terms of bone health and fracture risk. There was a small but significant association between vitamin D status at baseline and disease motor severity at 36 months. Show more

Keywords: Balance, cognition, disease progression, fall, 25-hydroxy vitamin D, Parkinson’s disease, vitamin D

DOI: 10.3233/JPD-171122

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 669-675, 2017

Authors: Kim, Iris Y. | O’Reilly, Éilis J. | Hughes, Katherine C. | Gao, Xiang | Schwarzschild, Michael A. | Ascherio, Alberto

Article Type: Research Article

Abstract: Background: Caffeine intake has been associated with a lower risk of Parkinson’s disease (PD). This association is robust in men, but inconsistent in women due to a possible interaction with post-menopausal hormone (PMH) use. Objective: To (1) evaluate the association between caffeine intake and PD risk and (2) assess potential effect modification of the association by PMH use among women. Methods: We examined associations between caffeine intake and incident PD risk in the Nurses’ Health Study (NHS) (N = 121,701 women) and the Health Professionals Follow-up Study (HPFS) (N = 51,529 men). Dietary data on coffee and caffeine …from other sources were collected every four years using a validated semi-quantitative food frequency questionnaire for both cohorts. Information on lifestyle and incident PD diagnosis was updated biennially and PD diagnoses were confirmed by medical record review. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards models. Results: We documented a total of 1,219 PD cases over the follow-up period. The multivariable-adjusted HR comparing the highest to lowest quintile of caffeine intake was 0.50 (95% CI: 0.37, 0.68; P trend <0.0001) in the HPFS. Among women, there was a suggestion of an interaction between coffee intake and PMH use (P  = 0.08). In the pooled analyses combining men and women who have never used PMH, the risk of PD was lower as coffee intake increased (P trend <0.001). Conclusions: Our results support previous findings that increased caffeine intake may be associated with a decreased PD risk in men and women who have never used PMH. Show more

Keywords: Parkinson’s disease, caffeine, estrogens, Health Professionals Follow-up Study; Nurses’ Health Study

DOI: 10.3233/JPD-171175

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 677-684, 2017

Authors: Berk, Sarah | Greco, Brittany L. | Biglan, Kevin | Kopil, Catherine M. | Holloway, Robert G. | Meunier, Claire | Simuni, Tanya

Article Type: Research Article

Abstract: Background: Challenges in clinical trial recruitment threaten the successful development of improved therapies. This is particularly true in Parkinson’s disease (PD) studies of disease modification where the population of interest is difficult to find and study design is more complex. Objective: This paper seeks to understand how STEADY PD III, a National Institute of Neurological Disorders and Stroke (NINDS) funded phase 3 trial evaluating the efficacy of isradipine as a disease modifying agent for PD, was able to recruit their full target population 6 months ahead of schedule. Methods: STEADY PD III aimed to enroll 336 …individuals with early stage idiopathic PD within 18 months using 57 sites across the United States and Canada. The study included a 10% NIH minority recruitment goal. Eligible participants agreed to be followed for up to 36 months, complete 12 in-person visits and 4 telephone visits. A Recruitment Committee of key stakeholders was critical in the development of a comprehensive recruitment strategy involving: multi-modal outreach, protocol modifications and comprehensive site selection and activation. Efforts to increase site-specific minority recruitment strategies were encouraged through additional funding. Results: A total of 336 individuals, including 34 minorities, were enrolled within 12 months – 6 months ahead of the projected timeline. Quantitative analysis of recruitment activity questionnaires found that of the sites that completed them (n  = 54), (20.4%) met goals, (24.1%) exceeded goals, and (55.6%) fell below projected goals. Referral sources completed at time of screening indicate top four study referral sources as: site personnel (53.8%); neurologists (24%); Fox Trial Finder (10.2%); and communications from The Michael J. Fox Foundation (3.9%). Conclusions: STEADY PD III serves as an important example of methods that can be used to increase clinical trial recruitment. This research highlights a continued need to improve site infrastructure and dedicate more resources to increased participation of minorities in clinical research. Show more

Keywords: Recruitment methods, Parkinson’s disease, disease modifying trials

DOI: 10.3233/JPD-171199

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 685-693, 2017

Authors: Hug, Kristina | Johansson, Mats

Article Type: Research Article

Abstract: Obtaining informed consent in clinical trials can be challenging both for researchers and for patients, albeit in different ways. The challenge concerns not only how to provide the needed information, but also what information to focus on when dealing with individual patients who have different goals, needs, histories, etc. This paper aims to contribute to a better informed consent process for Parkinson’s patients taking part in first-in-human clinical trials of cell replacement therapies. It outlines a range of problems which patients and researchers may face in this process and provides practical advice to researchers engaged in such trials.

Keywords: Parkinson’s disease, cell-based therapy, clinical trial, informed consent, autonomy, research ethics

DOI: 10.3233/JPD-171141

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 695-702, 2017

Authors: Afshari, Mitra | Yang, Amy | Bega, Danny

Article Type: Research Article

Abstract: Background: Despite evidence for the benefits of exercise in Parkinson’s disease (PD), many patients remain sedentary for undefined reasons. Objective: To compare exercise habits, perceptions about exercise, and barriers to exercise in ‘low’ (<3 h/week) and ‘high’ (≥3 h/week) exercisers with PD. Methods: A 48-item survey was administered to PD patients at an outpatient academic center. Chi-squared tests were used to compare the percentage differences between low- and high-exercisers with two-sided tests and a significant level of 0.05. Results: 243 surveys were collected over three months; 28 were excluded due to incomplete data, leaving 215 to …be analyzed. 49.3% reported ‘low’-exercise and 50.7% reported ‘high’-exercise. High-exercisers participated in higher intensity exercise regimens (83.4% versus 32.1%, p ≤0.001). High-exercisers were more likely to start exercising after being diagnosed (54.2% versus 27.8%, p  < 0.001), whereas low-exercisers were more likely to reduce their amount of exercise (40.2% versus 15.9%, p  < 0.001). Low-exercisers required more motivating factors. Both groups benefited from having a significant other or a personal trainer motivate them, and both were more likely to exercise if their neurologist encouraged them. Low-exercisers reported twice as many barriers as high-exercisers (p  = 0.001). Barriers that were significantly more common in low-exercisers were: lacking someone to motivate them (33.3% versus 10.5%, p  < 0.001), fatigue (20.8% versus 15.2%, p  = 0.005), and depression (16.7% versus 7.6%, p  = 0.045). Conclusions: There are significant differences between people with PD who exercise regularly and those who do not in terms of motivators and barriers. These findings should be considered when tailoring recommendations for PD patients to encourage exercise, and in designing future interventions. Show more

Keywords: Adult, exercise, falls, Parkinson’s disease, physical activity, quality of life

DOI: 10.3233/JPD-171173

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 703-711, 2017

Authors: Schmidt, Nele | Paschen, Laura | Deuschl, Günther | Witt, Karsten

Article Type: Research Article

Abstract: Background: Empathy describes the ability to infer and share emotional experiences of other people and is a central component of normal social functioning. Impaired empathy might be a non-motor symptom in Parkinson’s disease (PD). Objective: To examine empathic abilities and their relationship to clinical and cognitive functioning in PD patients. Methods: Empathy was measured in 75 non-demented PD patients and 34 age-matched healthy controls using a German version of the Interpersonal Reactivity Index. Moreover, we collected demographic and clinical data and conducted a comprehensive neuropsychological test battery. Results: PD patients had a significant lower …global empathy score than healthy controls. Furthermore, we found significant group differences for the cognitive empathy scales but not for the scales which are sensitive for affective empathy components. The empathy decrease was significantly higher in advanced Hoehn & Yahr stages. There were only sporadic significant correlations between empathy scores and cognitive variables. Conclusions: PD patients show a stage dependent empathy score decrease which is driven mainly by cognitive aspects of empathy. However, emotional empathy aspects are not reduced. Show more

Keywords: Parkinson’s disease, empathy, Theory of Mind, Interpersonal Reactivity Index

DOI: 10.3233/JPD-171083

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 713-718, 2017

Authors: Willows, Thomas | Dizdar, Nil | Nyholm, Dag | Widner, Håkan | Grenholm, Peter | Schmiauke, Ursula | Urbom, Anna | Groth, Kristina | Larsson, Jörgen | Permert, Johan | Kjellander, Susanna

Article Type: Research Article

Abstract: Background: Levodopa-carbidopa intestinal gel (LCIG; Duodopa® ) is used for continuous infusion in advanced Parkinson’s disease. To achieve optimal effect, the LCIG dose is individually titrated, traditionally conducted during hospitalization in Sweden. However, dose adjustment depends on surrounding conditions, physical activity, and emotional stress, which is why titration at home could be beneficial. Telemedicine (TM) using a video communication system offers alternative titration procedures, allowing LCIG initiation at home. Objective: Study objectives were to show the feasibility of TM for LCIG home titration, evaluate resource use, and assess patient, neurologist, and nurse satisfaction. Methods: Four clinics …enrolled 15 patients to observe efficiency and feasibility of TM-based monitoring. Results: Patient median (range) age was 67 (52–73) years and time since diagnosis was 10 (7–23) years. Median time between LCIG initiation and end of TM-assisted titration was 2.8 (2.0–13.8) days. Median time required for home titration by neurologists, nurses, and patients was (hours:minutes) 1 : 14 (0 : 29–1 : 52), 5 : 49 (2 : 46–10 : 3), and 8 : 53 (4 : 11–14 : 11), respectively. Neurologists and nurses considered this to be less time than required for hospital titration. TM allowed patients 92% free time from start to end of titration. Technical problems associated with TM contacts were rare, mostly related to digital link, and quickly resolved. Patients, neurologists, and nurses were satisfied using TM. No serious adverse events were reported; there was one device complaint (tube occlusion). Conclusions: In this study, TM-assisted LCIG titration at home was resource-efficient, technically feasible, well-accepted and was deemed satisfactory by patients, neurologists, and nurses. Show more

Keywords: Advanced Parkinson’s disease, levodopa-carbidopa intestinal gel, LCIG, duodenal levodopa-carbidopa infusion, Duodopa, telemedicine, video communication system, home titration, routine patient care, healthcare resource utilization

DOI: 10.3233/JPD-161048

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 719-728, 2017

Authors: Studer, Valeria | Maestri, Roberto | Clerici, Ilaria | Spina, Letizia | Zivi, Ilaria | Ferrazzoli, Davide | Frazzitta, Giuseppe

Article Type: Research Article

Abstract: Background: Gait disturbances in Parkinson’s disease (PD) are highly disabling and poorly responsive to drugs, especially in advanced stages. While the efficacy of a treadmill training based on external feedback and cues (treadmill-plus) on gait disturbances in early PD stages is demonstrated, no definitive evidence exists about advanced stages. Objective: We aimed to evaluate the feasibility and the effects of a treadmill-plus training on gait disturbances in advanced PD. Methods: Two hundred and six PD patients from medium to more advanced Hoehn & Yahr stage (stage 2, n  = 79, stage 3 n  = 74, and stage 4 = 53) …who underwent a 4-week treadmill-plus training, were retrospectively identified. All patients were able to walk on a treadmill for one minute at 1.5 km/h, without support. Feasibility was evaluated by measuring safety, adverse events, and attrition rate. The effects of treatment were evaluated by assessing, both at enrolment and at the end of treatment, the on-land, self-paced 6-minute Walking Test (6MWT) and the gait parameters obtained from the treadmill during a 1.5 km/h trial. Results: All patients completed the treadmill-plus training and no adverse events were recorded, even among more disabled patients. After training, we observed a significant improvement in the 6MWT, an increase in step length and a reduction of cadence and step variability in the whole sample. After stratifying patients according to disease stage, we found that patients in more advanced stages experienced the same improvements in all gait parameters as patients in less advanced stages. Conclusions: Treadmill-plus training is well tolerated and may have a positive impact on many aspects of gait in more advanced PD stages. Show more

Keywords: Parkinson’s disease, rehabilitation, gait, treadmill, advanced disease stages

DOI: 10.3233/JPD-171126

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 729-739, 2017

Authors: Heldman, Dustin A. | Urrea-Mendoza, Enrique | Lovera, Lilia C. | Schmerler, David A. | Garcia, Xiomara | Mohammad, Mohammad E. | McFarlane, Maria Catalina U. | Giuffrida, Joseph P. | Espay, Alberto J. | Fernandez, Hubert H.

Article Type: Research Article

Abstract: Background: Clinical rating of bradykinesia in Parkinson disease (PD) is challenging as it must combine several movement features into a single score. Additionally, in-clinic assessment cannot capture fluctuations throughout the day. Objective: To evaluate the reliability and responsiveness of a motion sensor-based tablet app for objective bradykinesia assessment in clinic and at home as compared to clinical ratings. Methods: Thirty-two PD patients treated with subthalamic deep brain stimulation (DBS) were outfitted with a motion sensor on the index finger of the more affected hand to perform two repetitions of finger-tapping, hand opening-closing, and arm pronation-supination tasks …with DBS on and 10, 20, and 30 minutes after turning DBS off. Tasks were videotaped for blinded clinician rating using the Modified Bradykinesia Rating Scale (MBRS). Participants were then sent home with an app-based system to perform two repetitions of the same tasks six times per day spaced two hours apart, three days per week, for two weeks. Intraclass correlation (ICC) and minimal detectable change (MDC) were calculated. Results: As the effects of DBS wore off, motion sensors detected worsening of amplitude sooner than did clinician-rated MBRS for all three tasks. ICCs were significantly higher and MDCs were significantly lower for motion sensors in the clinic and at home than for clinician ratings (p  < 0.01). Conclusions: The tablet-based app demonstrated higher reliability and responsiveness in capturing bradykinesia-related tasks in the clinic and at home than did clinician ratings. This tool may enhance the assessment of novel therapies. Show more

Keywords: Parkinson’s disease, bradykinesia, telemedicine, technology

DOI: 10.3233/JPD-171159

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 741-747, 2017

Authors: Lennaerts, Herma | Groot, Marieke | Rood, Berna | Gilissen, Koen | Tulp, Hella | van Wensen, Erik | Munneke, Marten | van Laar, Teus | Bloem, Bastiaan R.

Article Type: Research Article

Abstract: Background: Parkinson’s Disease Nurse Specialists (PDNS) play an important role in the care for patients with Parkinson’s disease (PD) and their caregivers. Until now, there were no nursing guidelines in PD, and interventions were based solely on daily clinical practice because there is no evidence to support the merits of nursing interventions. Consequently, there is little uniformity in current care delivery. Objective: Developing a guideline for PDNS. Methods: We developed a guideline based on a questionnaire among PDNS and a literature review, supplemented with expert opinion plus the input of patients and caregivers. The questionnaire was …filled in by 97 PDNS and 51 generic nurses with knowledge of PD to identify barriers in PD nursing care. Subsequently, we did a systematic literature search and transformed these sources of information into practice recommendations, which were developed according to international standards for guideline development. Results: Based on the results of the questionnaire we identified seven specific core areas: defining the role of PDNS in terms of caseload, education, competences and care coordination; medication adherence; provision of information and education; coping; caregiver support; urogenital function and orthostatic hypotension. The systematic literature search identified 186 studies, of which 33 studies were finally analyzed. Furthermore, we developed practice recommendations based on good clinical practice for the following areas: self-care, mental functioning, mobility, nutrition, sexuality, work, sleep, palliative care and complementary (integrative) care. Conclusion: This guideline provide ground to harmonize care delivery by PDNS in clinical practice, and offer a foundation for future research. Show more

Keywords: Evidence-based medicine, Parkinson’s disease, Parkinson’s Disease Nurse Specialist, guideline

DOI: 10.3233/JPD-171195

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 749-754, 2017

Authors: Miocinovic, Svjetlana | Shoeb, Ali H. | Wang, Sarah | Byrd, Erica A. | Swann, Nicole C. | Pathak, Anupam | Ostrem, Jill L.

Article Type: Short Communication

Abstract: We demonstrate the feasibility of estimating clinical tremor scores using an eating utensil with motion-sensing and tremor-cancellation technology in thirteen patients with tremor. Three experts scored hand tremor using the modified Fahn- Tolosa-Marin (FTM) scale. A linear model was trained to estimate tremor severity using the recorded motion signals. The average neurologist FTM score was 1.6±0.7 for PD and 2.6±0.7 for ET patients. The average model score was 1.6±0.7 for PD and 2.6±0.6 for ET. Correlation coefficient between the clinical and model tremor scores was 0.91 (p  < 0.001). Motion data from an instrumented eating utensil accurately derived tremor ratings enabling …practical, objective daily monitoring. Show more

Keywords: Tremor, essential tremor, Parkinson’s disease, non-invasive device, Liftwear measurement

DOI: 10.3233/JPD-160929

Citation: Journal of Parkinson's Disease, vol. 7, no. 4, pp. 755-759, 2017