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

Authors: Bloem, Bastiaan R. | Brundin, Patrik

Article Type: Editorial

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

DOI: 10.3233/JPD-199006

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

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

Article Type: Other

DOI: 10.3233/JPD-199005

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

Authors: The International Parkinson Disease Genomics Consortium (IPDGC)

Article Type: Review Article

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

Keywords: IPDGC, Parkinson disease, genetics, genomics

DOI: 10.3233/JPD-191854

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

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

Article Type: Review Article

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

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

DOI: 10.3233/JPD-191763

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

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

Article Type: Systematic Review

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

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

DOI: 10.3233/JPD-191726

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

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

Article Type: Systematic Review

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

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

DOI: 10.3233/JPD-191784

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

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

Article Type: Research Article

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

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

DOI: 10.3233/JPD-191766

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

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

Article Type: Research Article

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

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

DOI: 10.3233/JPD-191765

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

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

Article Type: Research Article

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

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

DOI: 10.3233/JPD-191754

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

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

Article Type: Research Article

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

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

DOI: 10.3233/JPD-191758

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

Authors: Sakakibara, Satoko | Hashimoto, Rina | Katayama, Taiji | Kenjyo, Masakuni | Yokokawa, Yuki | Saito, Yufuko | Hirakawa, Akihiro | Ito, Mizuki | Nakamura, Tomohiko | Hara, Kazuhiro | Hashizume, Atsushi | Aiba, Ikuko | Inukai, Akira | Katsuno, Masahisa

Article Type: Research Article

Abstract: Background: Both Parkinson’s disease (PD) and multiple system atrophy (MSA) are neurodegenerative disorder affecting striatonigral system. Although various lines of evidence demonstrate that dopaminergic neuron degeneration emerges before the onset of motor symptoms in PD, preclinical/prodromal progression of neurodegeneration is far less understood in MSA. Objective: The aim of this study was to clarify the difference in the progression of dopaminergic degeneration in MSA and PD using dopamine transporter single-photon emission computed tomography (DAT SPECT). Methods: We analyzed longitudinal data of the specific binding ratio (SBR), a measure of striatal radiotracer uptake, in DAT SPECT from …7 patients with MSA-C, 5 patients with MSA-P, and 18 patients with PD. We performed 2.7±0.7 scans with an interval of 9.85±6.00 months for MSA and 2 scans with an interval of 2.16±0.16 years for PD. Results: The rate of SBR decline was faster in both subtypes of MSA compared with PD, but the value was similar between MSA-P and MSA-C. The estimated SBR at the onset of initial motor symptoms was lower in PD and MSA-P than in MSA-C, especially in the predominantly affected side. SBR of the predominantly affected side starts to decrease before the onset of motor symptoms in PD and MSA-P, whereas the initiation of SBR decline is around the onset in MSA-C individuals. The decline of SBR in the less affected side was not clearly shown before the onset in MSA-P or MSA-C. Conclusions: Our results suggest that the SBR in DAT SPECT analysis is an important pathophysiological marker reflecting the disease- and subtype-specific progression of dopaminergic degeneration in MSA and PD. Show more

Keywords: Parkinson’s disease, multiple system atrophy, DAT SPECT, striatonigral degeneration, prodromal stage, preclinical

DOI: 10.3233/JPD-191710

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 123-130, 2020

Authors: Tanaka, Yasuhiro | Tsuboi, Takashi | Watanabe, Hirohisa | Nakatsubo, Daisuke | Maesawa, Satoshi | Kato, Sachiko | Kajita, Yasukazu | Sato, Maki | Oodake, Reiko | Hattori, Makoto | Yamamoto, Masahiko | Wakabayashi, Toshihiko | Katsuno, Masahisa | Sobue, Gen

Article Type: Research Article

Abstract: Background: Speech disorders are among the most common adverse effects after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD) patients. However, longitudinal speech changes after STN-DBS are not fully understood. Objective: We performed a two-year prospective study on PD patients who underwent STN-DBS and analyzed changes in speech function to clarify factors predicting for speech deterioration. Methods: Twenty-five PD patients were assessed before and up to two years after STN implantation. Speech function was evaluated in the on-stimulation condition and 30 min after stimulation cessation using auditory-perceptual assessment. Patients who experienced overall worsening in speech …intelligibility or naturalness ≥1 point during follow-up were classified into a deteriorated group (n  = 16), with the remaining subjects being classified into a stable group (n  = 9). Cognitive and motor functions were also assessed. Results: The stable group had significantly better values of low volume, monoloudness, and asthenic voice subscores of the auditory-perceptual assessment in the on-stimulation condition compared with the off-stimulation condition. Imprecise consonants, excess loudness variation, and strained voice subscores were improved via cessation of stimulation in both groups. Before surgery, the deteriorated group had significantly lower scores in the Stroop Color-Word Test and Digit Span compared to the stable group. Conclusions: During follow-up, some subscores showed significant worsening in the on-stimulation condition in both groups. However, beneficial effects of STN-DBS on speech appeared to counterbalance negative effects of STN-DBS on speech function only in the stable group. Worse cognitive function may be a potential predictor for speech deterioration after STN-DBS in PD patients. Show more

Keywords: Parkinson’s disease, subthalamic nucleus deep brain stimulation, dysarthria, speech, voice, longitudinal change

DOI: 10.3233/JPD-191798

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 131-140, 2020

Authors: Gago, Miguel Fernandes | Azevedo, Olga | Guimarães, Andreia | Teresa Vide, Ana | Lamas, Nuno J. | Oliveira, Tiago Gil | Gaspar, Paulo | Bicho, Estela | Miltenberger-Miltenyi, Gabriel | Ferreira, Joaquim | Sousa, Nuno

Article Type: Research Article

Abstract: Background: Sporadic Parkinson’s disease (PD) patients have lower α -galactosidase A (α -GAL A) enzymatic activity and Fabry disease (FD) patients potentially carry an increased risk of PD. Objective: Determination of PD prevalence in FD and clinical, biochemical and vascular neuroimaging description of FD pedigrees with concomitant PD. Methods: Clinical screening for PD in 229 FD patients belonging to 31 families, harbouring GLA gene mutation p.F113L, and subsequent pedigree analysis. Gender-stratified comparison of FD+/PD+ patients with their family members with FD but without PD (FD+/PD–) regarding Mainz scores, plasma & leukocytes α -GAL A enzymatic …activity, urinary Gb3 and plasma Lyso-Gb3, vascular brain neuroimaging. Results: Prevalence of PD in FD was 1.3% (3/229) (3% in patients aged ≥50 years). Three FD patients, one female (73 years old) (P1) and two males (60 and 65 years old) (P2 and P3), three different pedigrees, presented akinetic-rigid PD, with weak response to levodopa (16% – 36%), and dopaminergic deficiency on 18F-DOPA PET. No pathogenic mutations were found in a PD gene panel. FD+/PD+ patients had worse clinical severity of FD (above upper 75% IQR in Mainz scores), and cortico-subcortical white matter/small vessel lesions. P3 patient was under enzyme therapy, started 1 year before PD diagnosis. P2-P3 patients had higher leucocyte α -GAL A activity (2,2-3 vs.1,0 (median)(nmol/h/mg)). Conclusion: We have shown a high prevalence of PD in a late-onset phenotype of FD, presenting high cerebrovascular burden and weak response to levodopa. Further studies will untangle how much of this PD phenotype is due to Gb3 deposition versus cerebrovascular lesions in the nigro-striatal network. Show more

Keywords: Fabry disease, Parkinson’s disease, GLA, α-galactosidase A, Gb3, brain magnetic resonance imaging

DOI: 10.3233/JPD-191704

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 141-152, 2020

Authors: Yoo, Sang-Won | Oh, Yoon-Sang | Yoo, Ji-Yeon | Ryu, Dong-Woo | Lee, Kwang-Soo | Shin, Na-Young | Kim, Joong-Seok

Article Type: Research Article

Abstract: Background: Cognitive impairment and cardiovascular dysautonomia are two major non-motor features of Parkinson’s disease (PD). They have been investigated separately and extensively, but their interactive outcomes have rarely been studied. Objective: The purpose of this study was to examine the association between central atrophy and cognition and to assess the influence of cardiovascular lability on this association in PD patients. Methods: Out of 151 early PD patients, 47 subjects were ultimately enrolled according to our selection criteria. Their cognitive status was examined by comprehensive neuropsychological tests assessing five domains of cognition. Supine and orthostatic blood pressures …were recorded during head-up tilt tests, and orthostatic mean arterial pressure change was calculated. Every patient underwent brain magnetic resonance imaging, and intercaudate nucleus ratio was obtained as a central atrophy surrogate marker. The associations and interactions between central atrophy, cognition, and blood pressure variability were analyzed. Results: Among 47 subjects, 20 (42.6%) had orthostatic hypotension. Attention/working memory, executive function, and delayed recall were inversely associated with central atrophy (r  = –0.332, p  = 0.028; r  = –0.314, p  = 0.038; r  = –0.399, p  = 0.024; respectively). In a multiple regression model, only attention/working memory was independently associated with central atrophy when modulated by orthostatic mean arterial pressure change (p  < 0.05). Conclusion: This study revealed that cardiovascular dysautonomia interacted with the inverse association between cerebral atrophy and cognition, and it reinforced its relationship. Interaction between these two non-motor features should be kept in mind in clinical practice, particularly in PD patients with co-morbid vascular factors. Show more

Keywords: Parkinson’s disease, subcortical atrophy, cardiovascular dysautonomia, cognition

DOI: 10.3233/JPD-191748

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 153-160, 2020

Authors: Hansen, Allan K. | Parbo, Peter | Ismail, Rola | Østergaard, Karen | Brooks, David J. | Borghammer, Per

Article Type: Research Article

Abstract: Background: Flortaucipir PET, a marker of tau tangles, has shown lower than expected cortical uptake in Parkinson’s disease (PD), than would be predicted from neuropathologic estimates of Alzheimer’s disease co-pathology. Instead, the most characteristic finding of flortaucipir imaging in PD is decreased uptake in the substantia nigra, reflecting reduction in its “off-target” binding to neuromelanin. We have previously reported these observations in cross-sectional studies. Objective: Here, we present two-year follow-up data of cortical and nigral flortaucipir uptake in PD patients. Methods: Seventeen PD patients received repeat flortaucipir PET two years after baseline. We interrogated vertex-based group-wise …cortical tracer binding (SUVRs) with a cerebellar reference using the general linear model while mean substantia nigra SUVRs were compared with volumes of interest group comparisons and voxel-wise group analyses using ANOVA. Finally, we performed linear regressions of tau load with changes in MoCA and UPDRS motor scores. Results: We found no significant changes in substantia nigra or cortex flortaucipir uptake in Parkinson’s disease patients over two years and no association with changes in cognitive symptoms. Signal reduction in the medial substantia nigra trended towards an association with worsening of motor symptoms. Conclusion: No significant increase in tau tangles occurred after a two-year follow-up of Parkinson’s disease patients using flortaucipir PET. Show more

Keywords: Parkinson’s disease, dementia, neurofibrillary tangles, melanins, positron emission tomography

DOI: 10.3233/JPD-191774

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 161-171, 2020

Authors: Snineh, Muneer Abu | Hajyahya, Amal | Linetsky, Eduard | Eitan, Renana | Bergman, Hagai | Israel, Zvi | Arkadir, David

Article Type: Research Article

Abstract: Background: A wide variety of conversion factors for a levodopa-equivalent-dose (LED) have been proposed for each Parkinson’s disease (PD) medication. The currently-used set of conversion factors is based on studies that relied on subjective experience or theoretical assumptions. This set was never validated in patients receiving polytherapy. Objectives: To use real-life data to identify an optimal set of conversion factors independent of prior assumptions regarding clinical efficacy of different medications. Methods: Retrospective analysis of data from 206 cognitively-preserved patients with advanced PD receiving polytherapy before deep brain stimulation (DBS) surgery. A nonlinear automated problem solver was …used to find a set of conversion factors that, when applied, minimized the coefficient of variation of LEDs in a relatively homogenous cohort of patients. Results: Independent and model-free evaluation of a wide range of possible sets of conversion factors to LED suggested a set of normalized conversion factors for immediate release levodopa (1.00), controlled release levodopa (0.88), and amantadine (1.23). A minimal clinical benefit of entacapone was observed for patients with motor fluctuations. Our analysis could not detect conversion factors for dopamine agonists and MAO-B inhibitors, possibly because their clinical contribution when added to levodopa is limited. Conclusions: Independent from previous studies and prior assumptions we show that the currently-used LED conversion factors for immediate release levodopa, controlled release levodopa and amantadine are largely correct and that dopamine agonists, MAO-B inhibitors and entacapone, given in addition to levodopa, have little additional clinical value for PD patients with motor fluctuations. Show more

Keywords: Parkinson’s disease, clinical pharmacology, levodopa, dopamine agonists, amantadine, retrospective study

DOI: 10.3233/JPD-191769

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 173-178, 2020

Authors: Stang, Cole D. | Turcano, Pierpaolo | Mielke, Michelle M. | Josephs, Keith A. | Bower, James H. | Ahlskog, J. Eric | Boeve, Bradley F. | Martin, Peter R. | Upadhyaya, Sudhindra G. | Savica, Rodolfo

Article Type: Research Article

Abstract: Background: Few studies have investigated the incidence of PSP and CBS in the population. Objective: To examine the incidence of and trends in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) in a population-based cohort of residents of Olmsted County, MN. Methods: We used the 1991-2005 population-based, Olmsted County Parkinsonism-cohort study, defined via the Rochester Epidemiology Project. A movement-disorder specialist reviewed medical records, to confirm PSP and CBS diagnoses. Results: We identified 21 patients with these diagnoses 1991-2005 : 18 (85.7%), PSP; 3 (14.3%), CBS. The median diagnosis age was 78 (range: 66-88). 13/21 (62.0%) were …male. MRI was performed pre-diagnosis in 11 patients (8 PSP and 3 CBD); 10 showed atrophy consistent with clinical diagnoses. We observed concordance between clinical and pathological diagnoses in two PSP patients who underwent autopsy. Combined incidence for PSP and CBS in Olmsted County was 3.1 per 100,000 person-years (2.6 per 100,000 person-years, PSP; 0.4 per 100,000 person-years, CBS). Incidence was higher in men (4.5, 95% CI, 2.0-7.0) than women (1.8, 95% CI, 0.5-2.9). A combined, significant trend of increasing incidence was observed between 1991 and 2005 (B=0.69, 95% CI 0.42, 0.96, p<0.001). Median time from symptom onset to death among both groups was 6 years (range PSP, 1-10 years; range CBS, 3-8 years). Conclusions: The combined incidence for PSP and CBS was 3.1 per 100,000 person-years, higher in men than women. We observed a significant increase in both PSP and CBS, likely due to advancing imaging technology and improved diagnostic ability among physicians. Show more

Keywords: Progressive supranuclear palsy, corticobasal syndrome, incidence, population-based cohort

DOI: 10.3233/JPD-191744

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 179-184, 2020

Authors: Vidal-Martinez, Guadalupe | Chin, Brandon | Camarillo, Cynthia | Herrera, Gloria V. | Yang, Barbara | Sarosiek, Irene | Perez, Ruth G.

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) and multiple system atrophy (MSA) patients often suffer from gastrointestinal (GI) dysfunction and GI dysbiosis (microbial imbalance). GI dysfunction also occurs in mouse models of PD and MSA. Objectives: To assess gut dysfunction and dysbiosis in PD subjects as compared to controls, identify potential shared microbial taxa in humans and mouse models of PD and MSA, and to assess the effects of potential therapies on mouse GI microbiota. Methods: In this human pilot study, GI function was assessed by fecal consistency/frequency measured using the Bristol Stool Form Scale and GI transit time …assessed using Sitzmarks pills and abdominal radiology. Human and mouse microbiota were analyzed by extracting fecal genomic DNA followed by 16S rRNA sequencing. Results: In our PD patients genera Akkermansia significantly increased while a trend toward increased Bifidobacterium and decreased Prevotella was observed. Families Bacteroidaceae and Lachnospiraceae and genera Prevotella and Bacteroides were detected in both humans and PD mice, suggesting potential shared biomarkers. In mice treated with the approved multiple sclerosis drug, FTY720, or with our FTY720-Mitoxy-derivative, we saw that FTY720 had little effect while FTY720-Mitoxy increased beneficial Ruminococcus and decreased Rickenellaceae family. Conclusion: Akkermansia and Prevotellaceae data reported by others were replicated in our human pilot study suggesting the use of those taxa as potential biomarkers for PD diagnosis. The effect of FTY720-Mitoxy on taxa Rikenellaceae and Ruminococcus and the relevance of S24-7 await further evaluation. It also remains to be determined if mouse microbiota have predictive power for human subjects. Show more

Keywords: Microbiota, Parkinson’s disease, multiple system atrophy, FTY720, FTY720-Mitoxy, transgenic mouse models

DOI: 10.3233/JPD-191693

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 185-192, 2020

Authors: Martin-Ruiz, Carmen | Williams-Gray, Caroline H. | Yarnall, Alison J. | Boucher, John J. | Lawson, Rachael A. | Wijeyekoon, Ruwani S. | Barker, Roger A. | Kolenda, Claire | Parker, Craig | Burn, David J. | Von Zglinicki, Thomas | Saretzki, Gabriele

Article Type: Research Article

Abstract: Background: Cognitive decline is a frequent complication of Parkinson’s disease (PD) and the identification of predictive biomarkers for it would help in its management. Objective: Our aim was to analyse whether senescence markers (telomere length, p16 and p21) or their change over time could help to better predict cognitive and motor progression of newly diagnosed PD patients. We also compared these senescence markers to previously analysed markers of inflammation for the same purpose. Methods: This study examined the association of blood-derived markers of cell senescence and inflammation with motor and cognitive function over time in an …incident PD cohort (the ICICLE-PD study). Participants (154 newly diagnosed PD patients and 99 controls) underwent physical and cognitive assessments over 36 months of follow up. Mean leukocyte telomere length and the expression of senescence markers p21 and p16 were measured at two time points (baseline and 18 months). Additionally, we selected five inflammatory markers from existing baseline data. Results: We found that PD patients had shorter telomeres at baseline and 18 months compared to age-matched healthy controls which also correlated to dementia at 36 months. Baseline p16 levels were associated with faster rates of motor and cognitive decline over 36 months in PD cases, while a simple inflammatory summary score at baseline best predicted cognitive score over this same time period in PD patients. Conclusion: Our study suggests that both inflammatory and senescence markers (p16) are valuable predictors of clinical progression in PD patients. Show more

Keywords: Parkinson’s disease, telomere length, senescence, p16, p21, inflammation, biomarker, cognitive impairment, dementia

DOI: 10.3233/JPD-191724

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 193-206, 2020

Authors: Rompen, Lonneke | de Vries, Nienke M. | Munneke, Marten | Neff, Carolyn | Sachs, Todd | Cedrone, Steve | Cheves, Jason | Bloem, Bastiaan R.

Article Type: Research Article

Abstract: Background: Early 2014, Kaiser Permanente decided to adopt an innovative model for network-based allied healthcare for persons with Parkinson’s disease (PD), based on the principles of the Dutch ParkinsonNet. Objective: We present the interventions that were performed to implement this method at Kaiser Permanente and we show the first outcomes based on these interventions. Methods: In this study, 57 physical therapists, 18 speech therapists and 20 occupational therapists, as well as 13 medical centers across the state of California were included. Nine interventions were performed more or less simultaneously, including training and education of healthcare providers …and patients, a train the trainer curriculum, organizing IT, streamlining referral processes and building networks. Results: At the start, less than 30% of the patients within the Southern California Region received specialized allied health treatment (consisting of, i.e., gait training, voice training or guidance in activities of daily life). After one year, almost 55% of patients received specialized allied health treatment. In the second year, this number increased to just under 67%, suggesting a sustained concentration of care (the second core component of networked care). This can be seen as a first indicator for successful implementation of the ParkinsonNet network at Kaiser Permanente. Conclusions: The importance of these findings lies in the fact that a healthcare innovation that proved effective in one country can be transferred successfully to another country and to another healthcare system. Show more

Keywords: Networks, integrated care, health reform, Parkinson’s disease, ParkinsonNet, Kaiser Permanente

DOI: 10.3233/JPD-191620

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 207-212, 2020

Authors: Suzuki, Keisuke | Okuma, Yasuyuki | Uchiyama, Tomoyuki | Miyamoto, Masayuki | Haruyama, Yasuo | Kobashi, Gen | Sakakibara, Ryuji | Shimo, Yasushi | Hatano, Taku | Hattori, Nobutaka | Yamamoto, Toshimasa | Hirano, Shigeki | Yamamoto, Tatsuya | Kuwabara, Satoshi | Kaji, Yoshiaki | Fujita, Hiroaki | Kadowaki, Taro | Hirata, Koichi

Article Type: Research Article

Abstract: Background: In Parkinson’s disease (PD) patients, the factors related to weight loss remain unclear. Objective: To investigate determinants of low body mass index (BMI) in PD patients. Methods: We identified factors associated with low BMI in PD patients in a multicenter case-control study. A total of 435 PD patients and 401 controls were included. Results: The mean BMI was significantly lower in PD patients than in controls (22.0±3.4 kg/m2 vs. 25.4±4.3 kg/m2 ), with an adjusted odds ratio (AOR) of 3.072 (95% CI, 2.103–4.488; p  < 0.001) for low BMI (<22 kg/m2 ) in PD. Compared to …the high-BMI PD group (>22 kg/m2 ), the low-BMI PD group (<22 kg/m2 ) had more women; a longer disease duration; higher revised Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) II and IV scores; an increased levodopa equivalent dose (LED); and increased constipation, visual hallucination, dysphagia, dyskinesia and wearing off rates. There were no between-group differences in depression, anhedonia, apathy, sleep problems and daytime sleepiness. Multivariable analysis showed that visual hallucination (AOR, 2.408; 95% CI, 1.074–5.399; p  = 0.033) and the MDS-UPDRS IV (AOR, 1.155; 95% CI, 1.058–1.260; p  = 0.001) contributed to low BMI after controlling for clinical factors. In a second model, visual hallucination (AOR, 2.481; 95% CI, 1.104–5.576; p  = 0.028) and dyskinesia (sum of the MDS-UPDRS 4.3–4.6) (AOR, 1.319; 95% CI, 1.043–1.668; p  = 0.021) significantly contributed to low BMI. Conclusion: PD patients were 3 times more likely than healthy controls to have a low BMI. Motor complications, particularly dyskinesia, and visual hallucination were significantly associated with low BMI in PD patients. Show more

Keywords: Parkinson’s disease, body mass index, visual hallucination, dyskinesia, motor complication

DOI: 10.3233/JPD-191741

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 213-221, 2020

Authors: van den Heuvel, Lieneke | Dorsey, Ray R. | Prainsack, Barbara | Post, Bart | Stiggelbout, Anne M. | Meinders, Marjan J. | Bloem, Bastiaan R.

Article Type: Research Article

Abstract: Clinical decision making for Parkinson’s disease patients is supported by a combination of three distinct information resources: best available scientific evidence, professional expertise, and the personal needs and preferences of patients. All three sources have clear value but also share several important limitations, mainly regarding subjectivity, generalizability and variability. For example, current scientific evidence, especially from controlled clinical trials, is often based on selected study populations, making it difficult to translate the outcome to the care for individual patients in everyday clinical practice. Big data, including data from real-life unselected Parkinson populations, can help to bridge this information gap. Fine-grained …patient profiles created from big data have the potential to aid in identifying therapeutic approaches that will be most effective given each patient’s individual characteristics, which is particularly important for a disorder characterized by such tremendous interindividual variability as Parkinson’s disease. In this viewpoint, we argue that big data approaches should be acknowledged and harnessed, not to replace existing information resources, but rather as a fourth and complimentary source of information in clinical decision making, helping to represent the full complexity of individual patients. We introduce the ‘quadruple decision making’ model and illustrate its mode of action by showing how this can be used to pursue precision medicine for persons living with Parkinson’s disease. Show more

Keywords: Big data, data-driven science, evidence-based medicine, Parkinson’s disease, machine learning, personalized medicine, precision medicine, shared decision making

DOI: 10.3233/JPD-191712

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 223-231, 2020

Authors: Amundsen Huffmaster, Sommer L. | Lu, Chiahao | Tuite, Paul J. | MacKinnon, Colum D.

Article Type: Research Article

Abstract: Background: It has been hypothesized that freezing of gait (FOG) in people with Parkinson’s disease (PD) is due to abnormal coupling between posture and gait. Objective: In this study, we examined the relationship between anticipatory postural adjustments (APAs) preceding gait initiation and the kinematics of the first two steps between people with FOG and without FOG. Methods: The kinetics and kinematics of self-initiated gait were recorded in 25 people with PD (11 with FOG, 14 without FOG). Outcome variables included the amplitude and timing of the ground reaction forces (GRFs), center of pressure (CoP) shifts and …the spatial and temporal characteristics of the first and second steps. Results: The magnitude and timing of the APA phase of gait initiation were not significantly different between participants with and without FOG, yet the first step in the FOG group was distinguished by a significantly wider and less variable first step width, followed by a subsequent wider and shortened second step with reduced toe clearance. Multiple linear regression showed that the relationship between the initial conditions (stance width), APAs (posterior shift of the CoP) and the kinematics of the first step were different between groups with a significantly increased slope in the FOG group. Conclusion: These findings demonstrate that the transition from standing to walking is different between those with and without FOG and that alterations in the initial conditions or APAs are more likely to impact the execution of the two steps in people with FOG. Show more

Keywords: Gait initiation, Parkinson’s disease, anticipatory postural adjustments, stepping

DOI: 10.3233/JPD-191649

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 233-243, 2020

Authors: Peterson, Daniel S. | Mancini, Martina | Fino, Peter C. | Horak, Fay | Smulders, Katrijn

Article Type: Research Article

Abstract: Background: Gait speed is an important outcome that relates to mobility, function, and mortality, and is altered in people with Parkinson’s disease (PwPD). However, changes in gait speed may not reflect changes in other important aspects of gait. Objective: To characterize which outcomes change concomitantly with walking speed in PwPD. This information can inform the choice of outcome variables for characterizing and tracking gait performance in this population. Methods: 67 PwPD and 40 neurotypical adults completed 2-minute overground walking bouts at comfortable and fast self-selected speeds. Eight inertial sensors were used to characterize gait and turning. …We identified a subset of participants (38 per group) where the PD participant’s “fast” walk was similar speed to neurotypical participants “comfortable” walk, facilitating an across-group gait comparison controlling for gait speed. Results: Walking at fast gait speed compared to comfortable lead to significant changes in stride length, cadence, and stride time variability, but not in steps to turn, trunk ROM, and trunk and lumbar stability in PwPD. Sub-group analyses showed that despite walking at a similar speed as neurotypical adults, PwPD exhibit altered turning outcomes, lumbar stability, and stride length/cadence. Conclusions: Gait speed is a critical outcome for characterizing mobility. However, in PwPD, several important outcomes do not exhibit a uniform relationship with gait speed, and remain altered compared to neurotypical adults despite “normalizing” walking speed. Given the complex relationship between gait speed and other gait quality measures, care should be taken when choosing outcome measures to characterize the breadth of gait abnormality in PwPD. Show more

Keywords: Gait, kinematics, Parkinson’s disease, speed

DOI: 10.3233/JPD-191682

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 245-253, 2020

Authors: Hermann, Wiebke | Flemming, Theresa | Brandt, Moritz D. | Langner, Simona | Reichmann, Heinz | Storch, Alexander

Article Type: Research Article

Abstract: Background: Periodic limb movements in sleep (PLMS) are repetitive movements usually of the legs strongly associated with Restless-legs syndrome (RLS), which appear more frequently in males, older age and other sleep disturbances, such as sleep-disordered breathing (SDB). Patients with Parkinson’s disease (PD) suffer from various sleep disturbances including REM sleep behavior disorder, RLS and PLMS. Although a dopaminergic pathophysiology of PLMS is discussed, no systematic data on PLMS side-to-side distribution in PD and its correlation with asymmetry of motor symptoms are available. Objective: This study aimed at elucidating PLMS asymmetry in correlation to that of motor symptoms in …PD compared to SDB and RLS. Methods: Cross-sectional, retrospective analysis of two polysomnography (PSG) recordings per patient scoring PLMS separately for both legs. Results: Of 105 patients (44 PD, 44 age- and sex-matched SDB and 17 RLS patients) PLMS measures (number of PLM, PLM-Index, PLM-arousal index) showed significant side-to-side differences in all disease entities in both PSGs (P  < 0.001; Wilcoxon rank test). PLM-Index asymmetry (PLM-I difference of >5/h between both sides) was observed less frequently in PD (34% of patients) compared to RLS (77% , P  < 0.05) and SDB (59% , P  < 0.05; χ 2 test). In asymmetric PD patients, predominant side of PLMS was more stable than in SDB and RLS comparing the two PSGs, but we did not detect an agreement between PLMS predominant side with that of motor symptoms in PD patients. Conclusions: Only the minority of PD patients shows asymmetric PLMS distribution with relatively high night-to-night stability but no correlation with motor symptom asymmetry. Show more

Keywords: Parkinson’s disease, sleep-disordered breathing, periodic limb movements in sleep (PLMS), Willis-Ekbom disease, Restless-legs-syndrome

DOI: 10.3233/JPD-191667

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 255-266, 2020

Authors: Olsson, Tomas T. | Svensson, Martina | Hållmarker, Ulf | James, Stefan | Deierborg, Tomas

Article Type: Research Article

Abstract: Background: Physical activity is associated with reduced risk of Parkinson’s disease (PD). The explanations for this association are not completely elucidated. We use long-term PD-incidence data from long-distance skiers to study the relationship between exercise and PD. Objective: We aimed to investigate if physical activity is associated with long-term lower risk of PD and if this association could be explained by physically active people being able to sustain more PD neuropathology before clinical symptoms, a motor reserve. Methods: Using a prospective observational design, we studied whether long-distance skiers of the Swedish Vasaloppet (n  = 197,685), exhibited reduced …incidence of PD compared to matched individuals from the general population (n  = 197,684) during 21 years of follow-up (median 10, interquartile range (IQR) 5–15 years). Results: Vasaloppet skiers (median age 36.0 years [IQR 29.0–46.0], 38% women) had lower incidence of PD (HR: 0.71; 95 % CI 0.56–0.90) compared to non-skiers. When reducing risk for reverse causation by excluding PD cases within the first five years from race participation, there was still a trend for lower risk of PD (HR: 0.80; 95 % CI 0.62–1.03). Further, the PD prevalence converged between skiers and non-skiers after 15 years of follow-up, which is more consistent with a motor reserve in the physically active rather than neuroprotection. Conclusions: A physical active lifestyle is associated with reduced risk for PD. This association weakens with time and might be explained by a motor reserve among the physically active. Show more

Keywords: Physical activity, exercise, Parkinson’s disease, motor reserve

DOI: 10.3233/JPD-191762

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 267-274, 2020

Authors: Pintér, Dávid | Forjaz, Maria João | Martinez-Martin, Pablo | Rodriguez-Blazquez, Carmen | Ayala, Alba | Juhász, Annamária | Harmat, Márk | Janszky, József | Kovács, Norbert

Article Type: Research Article

Abstract: Background: Several scales are available for rating the severity of tremor at present. However, the sensitivity to change of these instruments has remained to be clarified. Objective: To compare the sensitivity of the Fahn-Tolosa-Marin Tremor Rating Scale, the Part III of the Movement Disorder Society-sponsored Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the MDS-UPDRS Tremor Scale to the effects of various antitremor treatments. Methods: Enrolling subjects with parkinsonism associated with tremor, we analyzed two scenarios: (1) tremor changes associated with acute levodopa challenge (n  = 287) and (2) a 12-month outcome of different treatment options (n  = 512) …including deep brain stimulation (n  = 146), levodopa/carbidopa intestinal gel infusion (n  = 30), and initiating (n  = 63) or adjusting oral antiparkinsonian medication (n  = 273). Changes in tremor scales were assessed by effect size values (Cohen’s d and eta-square). Results: Part B of the Fahn-Tolosa-Marin Tremor Rating Scale was the most sensitive to acute levodopa challenge (Cohen’s d = –1.04, η 2  = 0.12). However, Part A of the Fahn-Tolosa-Marin Tremor Rating Scale showed the highest effect size, which was a small one (Cohen’s d = –0.33, η 2  = 0.03), for detecting a treatment-related change in the severity of tremor during long-term follow-up. Conclusions: The Fahn-Tolosa-Marin Tremor Rating Scale has a better ability to capture changes due to levodopa challenge or antiparkinsonian treatment than MDS-UPDRS Part III or MDS-UPDRS Tremor Scale. Show more

Keywords: Parkinsonism, rating scales, treatment response, tremor

DOI: 10.3233/JPD-191800

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 275-282, 2020

Authors: Del Din, Silvia | Yarnall, Alison J. | Barber, Thomas R. | Lo, Christine | Crabbe, Marie | Rolinski, Michal | Baig, Fahd | Hu, Michele T. | Rochester, Lynn

Article Type: Research Article

Abstract: Background: Patients with REM sleep behavior disorder (RBD) have a high risk of developing PD, and thus can be used to study prodromal biomarkers. RBD has been associated with changes in gait; quantifying these changes using wearable technology is promising; however, most data are obtained in clinical settings precluding pragmatic application. Objective: We aimed to investigate if wearable-based, real-world gait monitoring can detect early gait changes and discriminate individuals with RBD from controls, and explore relationships between real-world gait and clinical characteristics. Methods: 63 individuals with RBD (66±10 years) and 34 controls recruited in the Oxford …Parkinson’s Disease Centre Discovery Study were assessed. Data were collected using a wearable device positioned on the lower back for 7 days. Real-world gait was quantified in terms of its Macrostructure (volume, pattern and variability (S2 )) and Microstructure (14 characteristics). The value of Macro and Micro gait in discriminating RBD from controls was explored using ANCOVA and ROC analysis, and correlation analysis was performed between gait and clinical characteristics. Results: Significant differences were found in discrete Micro characteristics in RBD with reduced gait velocity, variability and rhythm (p ≤0.023). These characteristics significantly discriminated RBD (AUC≥0.620), with swing time as the single strongest discriminator (AUC=0.652). Longer walking bouts discriminated best between the groups for Macro and Micro outcomes (p ≤0.036). Conclusions: Our results suggest that real-world gait monitoring may have utility as “risk” clinical marker in RBD participants. Real-world gait assessment is low-cost and could serve as a pragmatic screening tool to identify gait impairment in RBD. Show more

Keywords: Free-living, gait, prodromal, REM sleep behavior disorder, wearables

DOI: 10.3233/JPD-191773

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 283-299, 2020

Authors: Gan-Or, Ziv | Rao, Trisha | Leveille, Etienne | Degroot, Clotilde | Chouinard, Sylvain | Cicchetti, Francesca | Dagher, Alain | Das, Samir | Desautels, Alex | Drouin-Ouellet, Janelle | Durcan, Thomas | Gagnon, Jean-François | Genge, Angela | Karamchandani, Jason | Lafontaine, Anne-Louise | Sun, Sonia Lai Wing | Langlois, Mélanie | Levesque, Martin | Melmed, Calvin | Panisset, Michel | Parent, Martin | Poline, Jean-Baptiste | Postuma, Ronald B. | Pourcher, Emmanuelle | Rouleau, Guy A. | Sharp, Madeleine | Monchi, Oury | Dupré, Nicolas | Fon, Edward A.

Article Type: Research Article

Abstract: Background: Genetic, biologic and clinical data suggest that Parkinson’s disease (PD) is an umbrella for multiple disorders with clinical and pathological overlap, yet with different underlying mechanisms. To better understand these and to move towards neuroprotective treatment, we have established the Quebec Parkinson Network (QPN), an open-access patient registry, and data and bio-samples repository. Objective: To present the QPN and to perform preliminary analysis of the QPN data. Methods: A total of 1,070 consecutively recruited PD patients were included in the analysis. Demographic and clinical data were analyzed, including comparisons between males and females, PD patients …with and without RBD, and stratified analyses comparing early and late-onset PD and different age groups. Results: QPN patients exhibit a male:female ratio of 1.8:1, an average age-at-onset of 58.6 years, an age-at-diagnosis of 60.4 years, and average disease duration of 8.9 years. REM-sleep behavior disorder (RBD) was more common among men, and RBD was associated with other motor and non-motor symptoms including dyskinesia, fluctuations, postural hypotension and hallucinations. Older patients had significantly higher rates of constipation and cognitive impairment, and longer disease duration was associated with higher rates of dyskinesia, fluctuations, freezing of gait, falls, hallucinations and cognitive impairment. Since QPN’s creation, over 60 studies and 30 publications have included patients and data from the QPN. Conclusions: The QPN cohort displays typical PD demographics and clinical features. These data are open-access upon application (http://rpq-qpn.ca/en/ ), and will soon include genetic, imaging and bio-samples. We encourage clinicians and researchers to perform studies using these resources. Show more

Keywords: Parkinson disease, Quebec Parkinson Network, registry, biobank

DOI: 10.3233/JPD-191775

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 301-313, 2020

Authors: Rastgardani, Tara | Armstrong, Melissa J. | Gagliardi, Anna R. | Grabovsky, Arthur | Marras, Connie

Article Type: Research Article

Abstract: Background: OFF periods impair quality of life in Parkinson’s disease but the nature and degree of this impact is largely unquantified. Optimal treatment relies on assessing the experience and impact of these periods on patients and their carepartners. Objectives: To understand the experience and impact of OFF periods on their lives. Methods: Informed by qualitative interviews we designed questionnaires and surveyed neurologists, people with Parkinson’s disease and carepartners. Results: 50 general neurologists, 50 movement disorder neurologists, 442 patients (median disease duration 5 years) and 97 carepartners were included. The most common OFF symptoms reported …by patients and carepartners were stiffness, slowness of movement and changes in gait. Non-motor symptoms were less common. A higher proportion of carepartners reported each symptom. A minority of neurologists recognized pain, sweating and anxiety as possible symptoms of OFF periods. The three OFF symptoms most frequently designated as having great impact by people with Parkinson’s disease were changes in gait, slowness and stiffness. In contrast, cognitive impairment was most frequently rated as having great impact on carepartners. OFF periods were reported to impact many aspects of the lives of both patients and carepartners. Conclusions: In people with Parkinson’s disease of under 10 years duration, motor symptoms of OFF periods predominate in impact, however cognitive impairment has great impact on carepartners. Education is needed for neurologists regarding the non-motor aspects of OFF. The importance of involving carepartners in the assessment regarding OFF periods is supported by the higher frequency of symptom reporting by carepartners, and the significant impact on their lives. Show more

Keywords: Parkinson’s disease, fluctuations, impact, ‘off’ periods

DOI: 10.3233/JPD-191785

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 315-324, 2020

Authors: Fietzek, Urban M. | Schulz, Simon J. | Ziegler, Kerstin | Ceballos-Baumann, Andres O.

Article Type: Research Article

Abstract: Background: Freezing of gait is a highly disabling symptom in persons with Parkinson’s disease (PwP). Despite its episodic character, freezing can be reliably evaluated using the FOG score. The description of the minimal clinically relevant change is a requirement for a meaningful interpretation of its results. Objective: To determine the minimal clinically relevant change of the FOG score. Methods: We evaluated video recordings of a standardized freezing-evoking gait parkour, i.e., the FOG score just before and 30 minutes after the intake of a regular levodopa dose in a randomized blinded fashion. The minimal clinically relevant response …was considered a value of one or more on a 7-step Likert-type response scale [–3; +3] that served as the anchor. The minimal clinically relevant change was determined by ROC analysis. Results: 37 PwP (Hoehn & Yahr stages 2.5–4, 27 male, 10 female) were aged 68.2 years on average (range 45–80). Mean disease duration was 12.9 years (2–29 years). Minimum FOG score was 0 and Maximum FOG score was 29. Mean FOG scores before medication were 10.6, and 11.1 after medication intake, with changes ranging from –14.7 to +16.7. The minimal clinically relevant change (MCRC) for improvement based on expert clinician rating was three scale points with a sensitivity of 0.67 and a specificity of 0.96. Conclusions: The FOG score is recognized as a useful clinical instrument for the evaluation of freezing in the clinical setting. Knowledge of the MCRC should help to define responses to interventions that are discernible and meaningful to the expert physician and to the patient. Show more

Keywords: Parkinson’s disease, freezing, festination, assessment, minimal clinically relevant change

DOI: 10.3233/JPD-191783

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 325-332, 2020

Authors: Capato, Tamine T.C. | de Vries, Nienke M. | IntHout, Joanna | Barbosa, Egberto R. | Nonnekes, Jorik | Bloem, Bastiaan R.

Article Type: Research Article

Abstract: Background: Balance impairment in Parkinson’s disease (PD) improves only partially with dopaminergic medication. Therefore, non-pharmacological interventions such as physiotherapy are important elements in clinical management. External cues are often applied to improve gait, but their effects on balance control are unclear. Objective/Methods: We performed a prospective, single-blind, randomized clinical trial to study the effectiveness of balance training with and without rhythmical auditory cues. We screened 201 volunteers by telephone; 154 were assigned randomly into three groups: (1) multimodal balance training supported by rhythmical auditory stimuli (n  = 56) (RAS-supported multimodal balance training); (2) regular multimodal balance training without rhythmical …auditory stimuli (n  = 50); and (3) control intervention involving a general education program (n  = 48). Training was performed for 5 weeks, two times/week. Linear mixed models were used for all outcomes. Primary outcome was the Mini-BESTest (MBEST) score immediately after the training period. Assessments were performed by a single, blinded assessor at baseline, immediately post intervention, and after one and 6-months follow-up. Results: Immediately post intervention, RAS-supported multimodal balance training was more effective than regular multimodal balance training on MBEST (difference 3.5 (95% Confidence Interval (CI) 2.2; 4.8)), p  < 0.001). Patients allocated to both active interventions improved compared to controls (MBEST estimated mean difference versus controls 6.6 (CI 5.2; 8.0), p  < 0.001 for RAS-supported multimodal balance training; and 3.0 (CI 2.7; 5.3), p  < 0.001 for regular multimodal balance training). Improvements were retained at one-month follow-up for both active interventions, but only the RAS-supported multimodal balance training group maintained its improvement at 6 months. Conclusion: Both RAS-supported multimodal balance training and regular multimodal balance training improve balance, but RAS-supported multimodal balance training–adding rhythmical auditory cues to regular multimodal balance training–has greater and more sustained effects. Show more

Keywords: Parkinson’s disease, clinical trial, physical therapy, balance, postural control, cueing

DOI: 10.3233/JPD-191752

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 333-346, 2020

Authors: Bell, Jeremiah Fuller | Wu, Yingxing | Sollinger, Ann B. | Muthukattil, Ronex J. | Ferrara, Joseph M.

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) has been hypothesized to be associated with certain personality traits, including conscientiousness and punctuality. However, research aimed at quantifying these traits is largely derived from questionnaire-based personality inventories rather than real-world observations. Objective: To explore the presence of a parkinsonian personality profile by assessing the no-show rate of patients with PD versus other neurological disorders. Methods: We extracted data from our electronic health record for all neurology appointments over a 78-month interval. Additionally, we obtained primary care appointment data for the same patients over the same timeframe. For each appointment we collected …appointment date/time, check-in time, provider, age, sex, insurance type, days between appointment date and scheduling, diagnosis code, and no-show status. Results: 19,433 unique patients (400 with PD) accounting for a total of 252,347 outpatient appointments were included in our analysis. The overall no-show rate for PD patients was 3% versus 7.4% for patients with other neurologic disorders (OND). No show rates for PD patients were lower than those with OND for both neurology appointments (2.7% versus 13.6%) and for primary care visits (3.1% versus 5.9%). Conclusions: Patients with PD have lower no-show rates than patients with OND. Additionally, the no-show rate for patients with PD did not differ between their neurology and primary care appointments, confirming that patient’s personality rather than provider traits account for this difference, and supporting the presence of a parkinsonian personality. Show more

Keywords: Parkinson’s disease, parkinsonian personality, non-motor symptoms, dopamine dysfunction, no-show rates

DOI: 10.3233/JPD-191651

Citation: Journal of Parkinson's Disease, vol. 10, no. 1, pp. 347-350, 2020