Journal of Parkinson's Disease - Volume 8, issue 1

Authors: Chen, Honglei

Article Type: Review Article

Abstract: Despite recent successes in understanding the genetics of Parkinson’s disease (PD), the causes of late-onset sporadic PD remain elusive. Many of the epidemiologic findings on PD etiology have been challenged by alternative explanations such as reverse causation. This is mainly because PD often takes decades to develop before it can be diagnosed late in life. Convincing evidence shows that this prodromal stage of PD is characterized by various prodromal symptoms such as olfactory impairment and rapid-eye-movement sleep behavior disorder (RBD). As they likely reflect PD pathogenesis years, if not decades, before nigrostriatal involvement, research on these symptoms may represent an …unprecedented opportunity to dissect the etiology of PD. Using PD prodromal symptoms as intermediate phenotypes, we may be able to identify factors that contribute to the development of these symptoms and factors that modify their progression to clinical PD. Further, this line of research will also enable examinations of novel etiological hypotheses of PD development such as the microbiome and prion hypotheses. In this article, the author used olfactory impairment and RBD as examples to illustrate the promises and challenges of epidemiologic research on prodromal symptoms to understand PD etiology. Show more

Keywords: Epidemiology, Parkinson’s disease, olfaction disorders, REM sleep behavior disorder, risk factors, smoking

DOI: 10.3233/JPD-171238

Citation: Journal of Parkinson's Disease, vol. 8, no. 1, pp. 1-12, 2018

Authors: Coetzee, Gerhard A. | Pierce, Steven

Article Type: Article Commentary

Abstract: Genome-wide association studies of Parkinson’s disease have revealed polymorphic variants associated with closely mapped genes of interest. We propose here that those genes may only represent the tip of an iceberg of regulatory effects and do not necessary reflect disease relevance. To usefully interpret a risk locus, one needs to consider 5 dimensions of information, which represent the three-dimensional structure of chromatin (dimensions #1– 3), which is locally variable across time (dimension #4), and, most importantly, dependent on cell type and context (dimension #5).

Keywords: GWAS, enhancer, non-coding DNA, chromatin

DOI: 10.3233/JPD-171256

Citation: Journal of Parkinson's Disease, vol. 8, no. 1, pp. 13-15, 2018

Authors: Cooper, Jason F. | Van Raamsdonk, Jeremy M.

Article Type: Review Article

Abstract: Parkinson’s disease (PD) is an adult onset neurodegenerative disease that is characterized by selective degeneration of neurons primarily in the substantia nigra. At present, the pathogenesis of PD is incompletely understood and there are no neuroprotective treatments available. Accurate animal models of PD provide the opportunity to elucidate disease mechanisms and identify therapeutic targets. This review focuses on C. elegans models of PD, including both genetic and toxicant models. This microscopic worm offers several advantages for the study of PD including ease of genetic manipulation, ability to complete experiments rapidly, low cost, and ability to perform large scale screens …for disease modifiers. A number of C. elegans models of PD have been generated including transgenic worms that express α-synuclein or LRRK2, and worms with deletions in PRKN/pdr-1, PINK1/pink-1, DJ-1/djr-1.1/djr-1.2 and ATP13A2/catp-6. These worms have been shown to exhibit multiple phenotypic deficits including the loss of dopamine neurons, disruption of dopamine-dependent behaviors, increased sensitivity to stress, age-dependent aggregation, and deficits in movement. As a result, these phenotypes can be used as outcome measures to gain insight into disease pathogenesis and to identify disease modifiers. In this way, C. elegans can be used as an experimental tool to elucidate mechanisms involved in PD and to find novel therapeutic targets that can subsequently be validated in other models. Show more

Keywords: Parkinson’s disease, C. elegans, animal model, genetics, neurodegeneration, α-synuclein, parkin, PINK1, DJ-1, ATP13A2

DOI: 10.3233/JPD-171258

Citation: Journal of Parkinson's Disease, vol. 8, no. 1, pp. 17-32, 2018

Authors: König, Annekatrin | Vicente Miranda, Hugo | Outeiro, Tiago Fleming

Article Type: Review Article

Abstract:  Parkinson’s disease (PD) is a neurodegenerative disorder with complex etiology and variable pathology. While a subset of cases is associated with single-gene mutations, the majority originates from a combination of factors we do not fully understand. Thus, understanding the underlying causes of PD is indispensable for the development of novel therapeutics. Glycation, the non-enzymatic reaction between reactive dicarbonyls and amino groups, gives rise to a variety of different reaction products known as advanced glycation end products (AGEs). AGEs accumulate over a proteins life-time, and increased levels of glycation reaction products play a role in diabetic complications. It is now also …becoming evident that PD patients also display perturbed sugar metabolism and protein glycation, including that of alpha-synuclein, a key player in PD. Here, we hypothesize that anti-diabetic drugs targeting the levels of glycation precursors, or promoting the clearance of glycated proteins may also prove beneficial for PD patients. Show more

Keywords: Glycation, Maillard-reaction, Parkinson’s disease, alpha-synuclein

DOI: 10.3233/JPD-171285

Citation: Journal of Parkinson's Disease, vol. 8, no. 1, pp. 33-43, 2018

Authors: Bloem, Bastiaan R. | Ypinga, Jan H.L. | Willis, Allison | Canning, Colleen G. | Barker, Roger A. | Munneke, Marten | De Vries, Nienke M.

Article Type: Article Commentary

Abstract: The scientific evidence to support the value of a range of non-pharmacological interventions for people with Parkinson’s disease (PD) is increasing. However, showing unequivocally that specific interventions are better than usual care is not straightforward because of generic drawbacks of clinical trials. Here, we address these challenges, specifically related to the context of evaluating complex non-pharmacological interventions for people with PD. Moreover, we discuss the potential merits of undertaking “real world” analyses using medical claims data. We illustrate this approach by discussing an interesting recent publication in The Lancet Neurology , which used such an approach to demonstrate the value …of specialized physiotherapy for PD patients, over and above usual care physiotherapy. Show more

Keywords: Cost-effectiveness, medical claims, ParkinsonNet, Parkinson’s disease, physical therapy

DOI: 10.3233/JPD-171277

Citation: Journal of Parkinson's Disease, vol. 8, no. 1, pp. 45-58, 2018

Authors: Rosqvist, Kristina | Horne, Malcolm | Hagell, Peter | Iwarsson, Susanne | Nilsson, Maria H. | Odin, Per

Article Type: Research Article

Abstract: Background: It is unclear to which degree Levodopa (L-dopa) remains effective also in the late stage of Parkinson’s disease (PD) and to which degree motor fluctuations and dyskinesias remain a problem. Objective: To assess responsiveness of motor symptomatology to L-dopa in a group of patients with late stage PD. Moreover, to investigate the extent to which motor fluctuations and dyskinesias occur. Methods: Thirty PD patients in Hoehn and Yahr (HY) stages IV and V in “on” were included. L-dopa responsiveness was assessed with a standardized L-dopa test in the defined “off” and defined “on” states. Motor …function was assessed by the Unified PD Rating Scale (UPDRS) III and timed tests. Motor fluctuations and dyskinesias were assessed by the UPDRS IV. The participants were further monitored for 10 days with a mobile movement-analyses-system, the Parkinson’s Kinetigraph (PKG). The median (q1–q3) L-dopa equivalent daily dose (LEDD) was 799 (536–973) mg. Results: The UPDRS III score improved with ≥15% in 15 (50%) and with ≥30% in six (20%) participants during the L-dopa test. The median (q1–q3) UPDRS III score in “off” was 46 (37–53) and in “on” 36 (28–46). Twenty-one (70%) of the participants reported either predictable or unpredictable “off” fluctuations (items 36–37). The prevalence of dyskinesias (item 32, duration of dyskinesias ≥1) was 47%. The PKG indicated that dyskinesias primarily were mild and that a majority had a pronounced “off” symptomatology, spending a large proportion of the day either asleep or very inactive. Conclusions: Half of a group of patients with late stage PD had an L-dopa response of ≥15% on the UPDRS III. According to the UPDRS IV, a majority of the patients had motor fluctuations and about half had dyskinesias, although the PKG results suggested that these were not very severe. Show more

Keywords: Parkinson’s disease, levodopa, levodopa test, late stage, motor complications, fluctuations, dyskinesias

DOI: 10.3233/JPD-171181

Citation: Journal of Parkinson's Disease, vol. 8, no. 1, pp. 59-70, 2018

Authors: van der Zee, Sygrid | Vermeiren, Yannick | Fransen, Erik | Van Dam, Debby | Aerts, Tony | Gerritsen, Marleen J. | Spikman, Jacoba M. | van Laar, Teus | De Deyn, Peter P.

Article Type: Research Article

Abstract: Background: Lewy body disorders, including Parkinson’s disease (PD), Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB), are characterized by profound central and peripheral monoaminergic dysfunction. Objective: To investigate whether these alterations depend on dementia status, we measured cerebrospinal fluid (CSF) and serum monoamine and metabolite levels across subgroups of the cognitive spectrum, and evaluated their marker potential afterwards. Methods: In total, 153 subjects were included, of which 43 healthy controls (HC), 28 PD patients with normal cognition (PD-NC), 26 patients with PD and mild cognitive impairment (PD-MCI), 18 PDD patients, and 38 DLB patients. …The levels of monoamines and metabolites in paired CSF and serum samples were analyzed applying reversed-phase high-performance liquid chromatography with electrochemical detection. Results: Firstly, when comparing subgroups, CSF 3-methoxy-4-hydroxyphenylglycol (MHPG) levels were found lowest in HC and PD-NC groups and significantly higher in PDD/DLB patients. In addition, CSF 5-hydroxyindoleacetic acid (5-HIAA) levels differed significantly between HC and PD-MCI/PDD, and DLB patients (P ≤0.001), but not between HC and PD-NC patients. Secondly, when performing logistic regression, it was shown that particularly CSF/serum MHPG levels and the serum MHPG to noradrenaline (NA) ratio effectively differentiated between HC and (non-)pooled PD subgroups (AUC = 0.914–0.956), and PDD and DLB patients (AUC = 0.822), respectively. Furthermore, CSF 5-HIAA was the most discriminative parameter to differentiate between PD-NC and PD-MCI (AUC = 0.808), and, PD-NC and PDD subgroups (AUC = 0.916). Conclusions: Our data revealed that especially alterations of the noradrenergic neurotransmitter system could distinguish between Lewy body disorder subtypes, pinpointing CSF/serum MHPG and NA as potential stage markers across the cognitive spectrum. Show more

Keywords: 3-methoxy-4-hydroxyphenylglycol, noradrenaline, 5-hydroxyindoleacetic acid, dementia with Lewy bodies, Parkinson’s disease, Parkinson’s disease dementia, monoamines, biomarkers, RP-HPLC-ECD

DOI: 10.3233/JPD-171228

Citation: Journal of Parkinson's Disease, vol. 8, no. 1, pp. 71-84, 2018

Authors: Ma, Li-Jing | Xu, Ling-Li | Mao, Cheng-jie | Fu, Yun-Ting | Ji, Xiao-Yan | Shen, Yun | Chen, Jing | Yang, Ya-ping | Liu, Chun-Feng

Article Type: Research Article

Abstract: Background: Many optical coherence tomography (OCT) studies have reported alterations in the retinal nerve fiber layer (RNFL) in Parkinson’s disease (PD) and other neurodegenerative diseases. However, whether retinal alterations are a biomarker for PD is still controversial. Objective: To investigate potential correlations between PD and morphological changes in retina using OCT and to determine its usefulness as a biomarker of disease progression in PD. Methods: We performed a cross-sectional study on patients with PD (N = 37) and age-matched controls (N = 42), followed by a longitudinal study of the PD patients (N = 22) over approximately 2.5 years. Results: …The average retinal nerve fiber layer (RNFL) thickness (p  < 0.001), total macular thickness (p  = 0.001), and macular volume (p  = 0.001) were decreased in PD patients compared to controls and had further decreased at the follow-up visit (p  < 0.05 for all). The average RNFL thickness and the total thickness of macular were negatively correlated with age in PD patients at baseline. Linear regression analysis revealed that age (p  = 0.002, p  = 0.003, respectively) and LEDD (p  = 0.011, p  = 0.013, respectively) were correlated to total thickness and volume of macular in 22 PD patients in the follow-up study. However, no correlation was found between RNFL and other parameters. Conclusions: PD progression is associated with pronounced retinal structure changes, which can be quantified by OCT. Patterns of RNFL and macular damage detected by the noninvasive technology of OCT can be a useful biomarker for evaluating the progression of PD. Show more

Keywords: Macular, optical coherence tomography, Parkinson’s disease, retinal nerve fiber layer

DOI: 10.3233/JPD-171184

Citation: Journal of Parkinson's Disease, vol. 8, no. 1, pp. 85-92, 2018

Authors: Lee, Kelsey | Nguyen, Khanh-Dung | Sun, Chao | Liu, Mei | Zafar, Faria | Saetern, Jimmy | Flierl, Adrian | Tetrud, James W. | Langston, J. William | Dickson, Dennis | Schüle, Birgitt

Article Type: Research Article

Abstract: Background: Mutations in the leucine rich repeat kinase 2 (LRRK2 ) gene are among the most common genetic causes of Lewy body Parkinson’s disease (PD). However, LRRK2 mutations can also lead to a variety of pathological phenotypes other than typical PD, including relatively pure nigrostriatal cell loss without alpha-synuclein-positive Lewy bodies or Lewy neurites, progressive supranuclear palsy (PSP), and multiple system atrophy (MSA). The mechanisms behind this remarkable pleomorphic pathology are currently unclear. Objective: To genetically and pathologically characterize a case with a LRRK2 , p.Ile1371Val rare variant and pathologically proven MSA. Methods: From the …brain donation program at the Parkinson’s Institute and Clinical Center, we selected 26 brains with family history and a with clinicopathological diagnosis of PD (n  = 20), MSA (n  = 4), or PSP (n  = 2). We performed neuropathological evaluation, including alpha-synuclein and tau immunohistochemistry and sequenced 188 genes that have been reported as causative for or associated with neurodegenerative diseases. Results: We identified a known LRRK2 , p.Ile1371Val genetic variant in a case with clinically diagnosed and pathologically proven MSA. Neuropathology revealed that the olivopontocerebellar system was more affected than the striatonigral system. Conclusions: Our data suggest that genetic variants in the LRRK2 gene can present clinically and neuropathologically as MSA. One other LRRK2 genetic variant (LRRK2 , p.Ile2020Thr) has been reported with a neuropathological diagnosis of MSA. Interestingly, the LRRK2 variant (LRRK2 , p.Ile1371Val) identified here has been reported previously in a postmortem case with Lewy body PD. Future studies are critical to discover the mechanisms leading to different neurodegenerative trajectories both in neuronal and glial cell populations. Show more

Keywords: Alpha-synuclein, genetic risk factor, glial cytoplasmic inclusions, leucine-rich repeat kinase 2, LRRK2, multiple system atrophy, mutation, neuronal cytoplasmic inclusions, olivopontocerebellar degeneration, p.Ile1371Val

DOI: 10.3233/JPD-171237

Citation: Journal of Parkinson's Disease, vol. 8, no. 1, pp. 93-100, 2018

Authors: Simitsi, Athina | Koros, Christos | Moraitou, Marina | Papagiannakis, Nikos | Antonellou, Roubina | Bozi, Maria | Angelopoulou, Efthalia | Stamelou, Maria | Michelakakis, Helen | Stefanis, Leonidas

Article Type: Short Communication

Abstract: We compared phenotypic characteristics in 35 Greek patients with Parkinson’s disease (PD), carriers of GBA1 mutations (GBA-PD), with 35 Genetically Unidentified PD patients (GU-PD). We found a previously reported higher prevalence of cognitive impairment and a little appreciated more frequent bilateral onset of the disease in GBA-PD vs GU-PD. As far as the exposure to environmental factors, linked to PD, is concerned, our study hints to the possibility that pesticide exposure may be more common in GBA-PD patients, and possibly act synergistically with the mutation carrier status to trigger the disease.

Keywords: Cognitive decline, environmental exposure, glucocerebrosidase, Parkinson’s disease

DOI: 10.3233/JPD-171221

Citation: Journal of Parkinson's Disease, vol. 8, no. 1, pp. 101-105, 2018

Authors: Mantri, Sneha | Fullard, Michelle E. | Duda, John E. | Morley, James F.

Article Type: Research Article

Abstract: Background: Physical activity and exercise improve outcomes in Parkinson disease (PD), however little is known about activity levels in early PD patients. Objective and Methods: We examined self-reported activity scores and examined associations with clinical characteristics in 383 PD subjects and 175 healthy controls from the Parkinson Progression Markers Initiative (PPMI). Results: Activity scores were 8% lower for PD subjects than HC (162.6±86.2 vs 175.0±78.5, p  = 0.10). Higher scores were associated with younger age and male sex. Only 47% of PD subjects and 44% of HC reported activity consistent with standard recommendations for adults. …Conclusions: Our findings highlight the need to encourage exercise even in early PD. Show more

Keywords: Disease progression, Parkinson disease, Parkinson Progression Markers Initiative, physical activity

DOI: 10.3233/JPD-171218

Citation: Journal of Parkinson's Disease, vol. 8, no. 1, pp. 107-111, 2018

Authors: Ortelli, Paola | Ferrazzoli, Davide | Bera, Rossana | Caremani, Luca | Giladi, Nir | Maestri, Roberto | Frazzitta, Giuseppe

Article Type: Research Article

Abstract: Background: Parkinsonian patients in advanced stages of disease suffer from many motor and non-motor symptoms, whose responsiveness to dopamine replacement therapy and deep brain stimulation is poor. It is necessary to find complementary strategies in order to improve the clinical conditions of patients in advanced Parkinson’s disease (PD) stages. Objective: We aimed to understand whether an inpatient, motor-cognitive, multidisciplinary, aerobic, intensive and goal-based rehabilitation treatment (MIRT), specifically designed for PD, is effective for patients in advanced stages of disease. Methods: 638 Parkinsonian patients, hospitalized to undergo a 4-week MIRT, were retrospectively identified. According to the Hoehn …& Yahr (H&Y) scale, 496 were in H&Y stage 3 and 142 in H&Y stage 4-5. Outcome measures included: Unified Parkinson’s Disease Rating Scale (UPDRS), Berg Balance Scale (BBS), Timed Up and Go Test (TUG), Six Minute Walk Test (6MWT), and Parkinson’s Disease Disability Scale (PDDS). Results: At baseline all measures, except UPDRS IV, significantly worsened passing from H&Y stage 3 to H&Y stage 4-5 (p ≤0.002 all). After rehabilitation all outcome measures significantly improved in both groups of patients (p  < 0.0001 all). Comparing the amount of improvement in the two groups, significant differences were observed only for the changes in BBS and TUG (both p  < 0.0001 after adjustment), with a better improvement in the H&Y stage 4-5 group. Conclusions: A multidisciplinary, motor-cognitive, intensive and goal-based rehabilitation treatment, such as MIRT, could be an effective complementary treatment in PD patients in advanced stages of disease. Show more

Keywords: Advanced stages of disease, multidisciplinary treatment, Parkinson’s disease, rehabilitation

DOI: 10.3233/JPD-171247

Citation: Journal of Parkinson's Disease, vol. 8, no. 1, pp. 113-119, 2018

Authors: Bouça-Machado, Raquel | Maetzler, Walter | Ferreira, Joaquim J.

Article Type: Review Article

Abstract: Although yet poorly defined and often misused, the concept of functional mobility has been used in research studies as a more global and ecological outcome of patients’ health status. Functional mobility is a person’s physiological ability to move independently and safely in a variety of environments in order to accomplish functional activities or tasks and to participate in the activities of daily living, at home, work and in the community. Parkinson’s disease (PD) has a direct impact on patients’ motor control and on mobility in general. Even with optimal medical management, the progression of PD is associated with mounting impairments …at different levels of body function, causing marked limitations in a wide variety of activities, as well as a severe disability and loss of autonomy. Despite this, for everyday functioning PD patients need to have a good functional mobility that allow them to get around effortlessly in a reasonable amount of time to access to the same environments as others. This paper reviewed the concept of functional mobility applied to PD. This was done through an International Classification of Functioning and Disability (ICF) perspective. Recommendations to address the known factors that contribute to a poor functional mobility were outlined while suggestions for clinical practice and research were made. Show more

Keywords: Functional mobility, international classification of functioning, disability and health, Parkinson’s disease

DOI: 10.3233/JPD-171233

Citation: Journal of Parkinson's Disease, vol. 8, no. 1, pp. 121-130, 2018

Authors: van den Heuvel, Lieneke | Lim, Andrew S. | Visanji, Naomi P. | Huang, Jana | Ghate, Taneera | Mestre, Tiago A. | AlDakheel, Amaal | Connolly, Barbara S. | Gasca-Salas, Carmen | Kern, Drew S. | Jain, Jennifer | Slow, Elizabeth J. | Pondal, Margarita | Faust-Socher, Achinoam | Rogaeva, Ekaterina | Tomlinson, George | Lang, Anthony E. | Marras, Connie

Article Type: Research Article

Abstract: Background: With recent advances in the search for disease-modifying therapies for Parkinson’s disease (PD) the importance of identifying prodromal markers becomes greater. Non-manifesting LRRK2 mutation carriers (NMC) are at risk for developing PD, and provide a population in which to identify possible markers. Objective: The aim of this study was to test the hypothesis that NMC have differences in daily activity, fragmentation of sleep, arm swing asymmetry, and movement variability during walking, detectable by actigraphy, as compared to matched control subjects. Methods: Eleven NMC, fourteen PD patients (4 LRRK2 -PD, 10 idiopathic PD (iPD)), and …twenty-nine controls wore wristbands containing an accelerometer for seven days, and performed a daily walking task. Outcome measures included daily activity, fragmentation of activity, fragmentation of sleep, arm swing asymmetry during walking, and intra-individual variability. Results: Compared to healthy controls, both NMC and LRRK2 /iPD showed higher intra-individual variability in activity during walking compared to healthy controls. Individuals with LRRK2 -PD/iPD, but not NMC, tend to have lower activity levels, more arm swing asymmetry and less increase of arm swing with transition from slow to faster walking speed compared to healthy controls. Conclusion: Higher intra-individual variability of gait-associated movements might be a useful biomarker of prodromal PD. These results encourage replication in a larger sample and longitudinal analysis is warranted. Show more

Keywords: Actigraphy, high risk Parkinson, LRRK2 mutation, non-manifestingLRRK2 carrier, Parkinson’s disease, variability of gait

DOI: 10.3233/JPD-171151

Citation: Journal of Parkinson's Disease, vol. 8, no. 1, pp. 131-139, 2018

Authors: Conradt, Christian | Guo, Dianlin | Miclea, Anca | Nisslein, Thomas | Ismail, Chaim | Chatamra, Krai | Andersohn, Frank

Article Type: Research Article

Abstract: Background: The independent contribution of levodopa exposure and Parkinson’s disease (PD) to the risk of polyneuropathy is not established. Objective: This study investigated whether patients with newly diagnosed PD without previous exposure to antiparkinsonian drugs have higher prevalence of polyneuropathy than the general population. Methods: Using the UK General Practice Research Database, presence of polyneuropathy in the previous 3 years was assessed. Results: Of 5089 PD patients and 19,897 controls, polyneuropathy was confirmed in 15 PD patients (0.29% ) and 24 controls (0.12% ). Polyneuropathy prevalence was 2.4-fold higher in PD patients than controls. …Conclusions: In this observational study, PD patients had a higher prevalence of preexisting polyneuropathy that cannot be explained by adverse effects of antiparkinsonian drugs. Show more

Keywords: Polyneuropathy, Parkinson’s disease, observational study

DOI: 10.3233/JPD-161057

Citation: Journal of Parkinson's Disease, vol. 8, no. 1, pp. 141-144, 2018

Authors: Lee, Yang-Hyun | Lee, Jee-Eun | Ryu, Dong-Woo | Oh, Yoon-Sang | Lee, Kwang-Soo | Hong, Sung-Hoo | Kim, Joong-Seok

Article Type: Research Article

Abstract: Background: Urinary dysfunction is relatively common, however, is often underestimated and diagnosed by subjective questionnaires in patients with Parkinsonism. Objective: To determine the correlation between subjective urinary dysfunction and post-void residual urine volume in patients with Parkinson’s disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), and to assess the relationship between clinical characteristics and subjective or objective urinary dysfunction. Methods: A total of 196 patients with de novo Parkinsonism without urological and gynecological disorders were included. For all subjects, data were collected on sonographic post-void residual urine volume and urinary symptoms. All patients …were also assessed on motor symptom severity, cognitive and affective measurements, other nonmotor symptoms, 39-item Parkinson’s Disease Questionnaire, and renal functions. Results: Seventeen out of 196 parkinsonian patients showed abnormal post-void residual urine volumes, with ≥100 ml. The MSA group showed significantly higher post-void residual urine volume compared to the PD and PSP groups. Symptoms of the sense of incomplete emptying, weak urine stream, and nocturia were strongly correlated with post-void residual urine volume. Post-void residual urine volume was positively related to autonomic symptoms, other non-motor symptoms, patient activities of daily living, and negatively related to renal function. Conclusion: Increased post-void residual urine volumes were observed in small portion of early drug-naïve Parkinsonian patients, especially in MSA. Post-void residual urine volume was significantly related to subjective urinary and other autonomic dysfunctions. Voiding dysfunction is associated with not only end organ damage, but also other nonmotor dysfunctions and patient activities of daily living. Show more

Keywords: Parkinson’s disease, multiple system atrophy, progressive supranuclear palsy, urinary dysfunction, post-void residual urine

DOI: 10.3233/JPD-171254

Citation: Journal of Parkinson's Disease, vol. 8, no. 1, pp. 145-152, 2018

Authors: Kotagal, Vikas | Albin, Roger L. | Müller, Martijn L.T.M | Bohnen, Nicolaas I.

Article Type: Research Article

Abstract: Background: Medical comorbidities, including cardiovascular risk factors such as hypertension and diabetes, influence disease progression in Parkinson disease (PD) and may be variably present in different clinical populations. Objective/Methods: We conducted a retrospective nested case-control study of 29 Veterans with PD and 29 non-Veteran PD controls. The groups were matched for age, gender, and disease duration. Both groups underwent clinical and imaging testing as part of their participation in a larger cross-sectional PD observational study at our research center. Veterans were recruited primarily from movement disorders neurology clinics at the Ann Arbor Veterans Affairs (VA) Health System. Non-Veterans …were recruited primarily from analogous clinics at the University of Michigan Health System. We explored differences in cardiovascular risks factor burden between the groups. Results: Veterans with PD showed higher scores on the simplified Framingham 10-year general cardiovascular disease risk calculator (FR score; 27.3% (11.5) vs. 20.7% (6.8); t  = –2.66, p  = 0.011) and fewer years of self-reported education (14.5 (2.5) vs. 16.7 (2.6); t  = 3.33, p  = 0.002). After adjusting for age, disease duration, education, and the use of antihypertensive medications, Veterans showed higher FR scores (t  = 2.95, p  = 0.005) and a higher intra-subject ratio of FR score to age-and-gender normalized FR score (t  = 2.49, p  = 0.016), representing an elevated component of modifiable cardiovascular risk factor burden. Conclusion: Cardiovascular comorbidities are common in Veterans with PD and may be more severe than in non-Veteran PD populations. These findings merit replication in other representative cohorts. Veterans may be a preferred population for clinical trials evaluating cardiovascular risk factor management on PD progression. Show more

Keywords: Accidental falls, hypertension, Parkinson disease, veterans, white matter

DOI: 10.3233/JPD-171271

Citation: Journal of Parkinson's Disease, vol. 8, no. 1, pp. 153-160, 2018