Journal of Parkinson's Disease - Volume 7, issue 2

Authors: Almeida, Lorena R.S. | Valenca, Guilherme T. | Negreiros, Nádja N. | Pinto, Elen B. | Oliveira-Filho, Jamary

Article Type: Research Article

Abstract: Background: Falls are a debilitating problem for people with Parkinson’s disease (PD). Objectives: To compare clinical and functional characteristics of non-fallers, single and recurrent fallers (≥2 falls); to determine predictors of time to second fall; and to develop a predictive tool for identifying people with PD at different categories of falls risk. Methods: Participants (n  = 229) were assessed by disease-specific, self-report and balance measures and followed up for 12 months. Area under the receiver operating characteristic curves (AUC), Kaplan-Meier curves and log-rank test were performed. Selected predictors with p  < 0.10 in univariate analysis were chosen …to be entered into the Cox regression model. Results: Eighty-four (37%) participants had ≥2 falls during the follow-up. Recurrent fallers significantly differed from single fallers. The final Cox model included history of ≥2 falls in the past year (Hazard Ratio [HR] = 3.94; 95% confidence interval [CI] 2.26–6.86), motor fluctuations (HR = 1.91; 95% CI 1.12–3.26), UPDRS activities of daily living (ADL) (HR = 1.10 per 1 point increase; 95% CI 1.06–1.14) and levodopa equivalent dose (LED) (HR = 1.09 per 100 mg increase; 95% CI 1.02–1.16). A 3-predictor tool included history of ≥2 falls in the past year, motor fluctuations and UPDRS ADL >12 points (AUC = 0.84; 95% CI 0.78–0.90). By adding LED >700 mg/day and Berg balance scale ≤49 points, a 5-predictor tool was developed (AUC = 0.86; 95% CI 0.81–0.92). Conclusions: Two predictive tools with moderate-to-high accuracy may identify people with PD at low, medium and high risk of falling recurrently within the next year. However, future studies to address external validation are required. Show more

Keywords: Parkinson disease, accidental falls, postural balance, risk factors

DOI: 10.3233/JPD-160934

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 313-324, 2017

Authors: Ossig, Christiana | Sippel, Daniel | Fauser, Mareike | Gandor, Florin | Jost, Wolfgang H. | Ebersbach, Georg | Storch, Alexander

Article Type: Research Article

Abstract: Background: Nonmotor symptoms (NMS) are known to fluctuate together with motor oscillations in advanced PD, but their timing and kinetics remains enigmatic. Objective: To evaluate timing and kinetics of NMS fluctuations. Methods: Analysis of diary data from 17 fluctuating PD patients. Diaries were completed by rating NMS as absent (defined herein as NMS On state) or present (NMS Off state) and motor function for every hour for 5 consecutive days. Timing and kinetics were analyzed by synchronizing motor Off periods and subsequent cross-classification of NMS Off periods for each motor Off hour into 2×2 contingency …tables. Results: We found clear temporal connections of NMS Off periods with motor Off periods only for anxiety/depression, concentration/attention deficiency and bladder urgency. Psychiatric NMS Off periods had a longer duration (median: 3–4 hours) compared to motor Off periods (2 hours; P  < 0.05, Mann-Whitney U-test). Conclusions: Our data on timing and kinetics of NMS fluctuations show close temporal connection with motor Off periods only for mood and cognitive symptoms. Variances in both timing and/or kinetics of NMS fluctuations might explain both the weak/absent correlations of NMS and motor symptom severity in fluctuating patients and the rather low rates of simultaneous switches between On and Off states for NMS and motor function. Show more

Keywords: Nonmotor symptoms, nonmotor fluctuations, timing, kinetics, motor complications, psychiatric symptoms, autonomic dysfunction, Parkinson’s disease

DOI: 10.3233/JPD-160996

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 325-330, 2017

Authors: Engen, Phillip A. | Dodiya, Hemraj B. | Naqib, Ankur | Forsyth, Christopher B. | Green, Stefan J. | Voigt, Robin M. | Kordower, Jeffrey H. | Mutlu, Ece A. | Shannon, Kathleen M. | Keshavarzian, Ali

Article Type: Research Article

Abstract: Background: Recent evidence suggests that Parkinson’s disease (PD) is associated with intestinal microbiota dysbiosis, abnormal intestinal permeability, and intestinal inflammation. Objective: Our study aimed to determine if these gut abnormalities are present in another synucleinopathy, multiple system atrophy (MSA). Methods: In six MSA and 11 healthy control subjects, we performed immunohistochemistry studies of colonic sigmoid mucosa to evaluate the intestinal barrier marker Zonula Occludens-1 and the endotoxin-related inflammation marker Toll-like-receptor-4 expression. We also assessed colonic sigmoid mucosal and fecal microbiota compositions using high-throughput 16S ribosomal RNA gene amplicon sequencing. Results: MSA subjects showed …disrupted tight junction protein Zonula Occludens-1 structure in sigmoid mucosa tissue suggesting intestinal barrier dysfunction. The lipopolysaccharide specific inflammatory receptor Toll-like-receptor-4 was significantly higher in the colonic sigmoid mucosa in MSA relative to healthy controls. Microbiota analysis suggested high relative abundance of gram-negative, putative “pro-inflammatory” bacteria in various family and genus level taxa, from the phylum Bacteroidetes and Proteobacteria, in MSA feces and mucosa. At the taxonomic level of genus, putative “anti-inflammatory” butyrate-producing bacteria were less abundant in MSA feces. Predictive functional analysis indicated that the relative abundance of a number of genes involved in metabolism were lower in MSA feces, whereas the relative abundance of genes involved in lipopolysaccharide biosynthesis were higher in both MSA feces and mucosa compared to healthy controls. Conclusions: This proof-of-concept study provides preliminary evidence that like PD, MSA subjects display evidence of disrupted intestinal barrier integrity, increased marker of endotoxin-related intestinal inflammation, and pro-inflammatory colonic microbiota. Show more

Keywords: Multiple system atrophy, microbiota, colonic mucosa and feces, lipopolysaccharide, Zonula Occludens-1, Tolllike-receptor-4

DOI: 10.3233/JPD-160991

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 331-346, 2017

Authors: Yilmaz, Rezzak | Bayram, Ece | Ulukan, Çağrı | Altınok, Mustafa Kemal | Akbostancı, Muhittin Cenk

Article Type: Research Article

Abstract: Background: It has been suggested that appendectomy may modify the emergence of Parkinson’s disease (PD) by affecting the retrograde transport of α-synuclein (α-syn) from the gastrointestinal system. Objective: To explore the possible role of appendectomy on PD. Methods: The retrospective data of the 1625 patients (839 PD, 633 non-α-syn parkinsonism and 153 controls) were compared. Disease specific measures between PD patients with (n  = 69) and without (n  = 770) appendectomy were also evaluated. Results: The prevalence of appendectomy was not significantly lower in the PD group (8.2%) compared to the other groups (8.4% and …7.9%, p  = 0.98), and the odds of having PD against other diagnoses (OR) were not significantly different in the appendectomy group (OR = 0.99, p  = 0.96). No difference was determined between PD patients with and without appendectomy with respect to the age of disease onset, disease duration and severity. Appendectomy-first symptom interval was not determined to be related with PD diagnosis (hazard ratio = 1.12, p  = 0.39) and did not predict disease severity in the PD group (OR = 0.99, p  = 0.54). Age of appendectomy (lower or higher than 20) also did not affect future PD diagnosis (Relative Risk = 0.9, p  = 0.54) or the disease severity. Conclusions: The results of the study suggest no effect of appendectomy on the emergence and clinical manifestations of PD. The removal of the appendix is possibly not sufficient to suppress the exposure of the brain stem to α-syn via vagal retrograde transport. Further studies are needed to elucidate the role of appendix in PD. Show more

Keywords: Parkinson’s disease, appendectomy

DOI: 10.3233/JPD-171071

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 347-352, 2017

Authors: Mishima, Takayasu | Fukae, Jiro | Fujioka, Shinsuke | Inoue, Kotoe | Tsuboi, Yoshio

Article Type: Research Article

Abstract: Background: Gastrointestinal symptoms are one of the most common non-motor features of Parkinson’s disease (PD). Recently, a report from Taiwan revealed that irritable bowel syndrome (IBS) may be associated with an increased risk of developing PD; however, the prevalence of IBS in PD patients has not been fully evaluated. Rome III criteria are widely assessed with a questionnaire to determine functional gastrointestinal disorders. Objective: We assessed the prevalence of constipation and IBS in PD patients in our cohort using Rome III criteria. Methods: Between October 2014 and April 2015, 118 patients with PD were treated …at Fukuoka University Hospital and were enrolled in this study. Rome III criteria were used to diagnose constipation and IBS. Results: Constipation and IBS were detected in 32 (27.1%) and 20 patients (17.0%), respectively. The most common symptom related to constipation was straining during defecation (77.1%). Among constipation symptoms, patients’ self-awareness of constipation was mostly related to straining during defecation (odds ratio 5.27, 95% confidence interval 1.475–18.811). The number of constipation symptoms was correlated with the severity of the Hoehn-Yahr Stage (p  < 0.05) and total levodopa equivalent dose (p  < 0.05). Conclusions: This is the first report to investigate the prevalence of IBS in PD patients with Rome III criteria. We found a higher prevalence of IBS compared with the general population. The prevalence of constipation based on Rome III criteria was much lower than that reported in previous studies. Further studies are warranted to evaluate gastrointestinal symptoms in PD patients using comparable questionnaires. Show more

Keywords: Constipation, irritable bowel syndrome, Parkinson’s disease, Rome III diagnostic criteria

DOI: 10.3233/JPD-160982

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 353-357, 2017

Authors: Knudsen, Karoline | Fedorova, Tatyana D. | Bekker, Anne C. | Iversen, Peter | Østergaard, Karen | Krogh, Klaus | Borghammer, Per

Article Type: Research Article

Abstract: Background: Gastrointestinal function has received increased interest in the context of Parkinson’s disease (PD). Constipation is among the most frequent non-motor symptoms, but our understanding of the underlying pathology is limited. Subjective constipation correlates poorly with objective markers. Objective: The aims were to evaluate colonic transit time and volume in PD and to correlate these measures with subjective symptoms and gastric emptying. Methods: Thirty-two PD patients and 26 controls were included. Colonic transit time, computed tomography-based volume estimation, and gastric emptying were performed as objective markers of gastrointestinal function. Subjective gastrointestinal symptoms were evaluated by …three different questionnaires. Results: Seventy-nine percent of PD patients displayed prolonged colonic transit time (p  < 0.0001) and 66% of patients had significantly increased colonic volume (p  = 0.0002). Particularly the transverse and rectosigmoid segments were affected. There was no difference in gastric emptying time between groups. The prevalence of subjective constipation in PD patients was significantly lower and ranged from 3% to 38% depending on the type of questionnaire. Conclusions: Significantly delayed colonic transit time and increased volume were frequent findings in PD patients, and objective dysfunction was considerably more prevalent than subjective constipation symptoms. Also, the prevalence of subjective constipation varied widely depending upon which questionnaire was employed. These findings highlight the need for more research on how to define constipation in PD and also the need for improved understanding of the relationship between subjective symptoms and objective dysfunction. Show more

Keywords: Parkinson, constipation, gastrointestinal, non-motor symptom, transit time

DOI: 10.3233/JPD-161050

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 359-367, 2017

Authors: Ryu, Dong-Woo | Lee, Si-Hoon | Oh, Yoon-Sang | An, Jae-Young | Park, Jeong-Wook | Song, In-Uk | Lee, Kwang-Soo | Kim, Joong-Seok

Article Type: Research Article

Abstract: Background: Recent genetic and epidemiological studies have shown that there is a link between essential tremor and Parkinson’s disease (PD). However, there is a lack of data about the clinical features of PD developed from essential tremor. Objective: To explore and describe the clinical characteristics of Parkinson’s disease developed from essential tremor (ET-PD). Methods: Twenty-five ET-PD patients and 124 IPD controls were enrolled according to each criterion. Motor and non-motor features and dopamine transporter uptake were compared between the two groups. Results: Rest and action tremors were more severe in ET-PD patients than …in IPD patients. In addition, tremor disorder of first-degree relatives occurred more frequently in the ET-PD group than in the IPD group. A comparison between cases with ET-PD and IPD was not significant for striatal dopamine transporter uptake. Among the non-motor features, sleep disorder frequency, especially rapid-eye-movement sleep behavioral disorder, were lower in patients with ET-PD than in those with IPD, and smell identification test scores were higher in patients with ET-PD than in those with IPD. The prevalence of other non-motor symptoms did not differ between the two groups. Conclusion: This is the first comparison of motor and non-motor features between ET-PD and IPD. ET-PD and IPD have different characteristic motor and non-motor features from the nosologic perspective. Show more

Keywords: Parkinson’s disease, essential tremor, non-motor symptoms, REM sleep behavior disorder, olfactory dysfunction

DOI: 10.3233/JPD-160992

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 369-376, 2017

Authors: Kelley, Kristen D. | Peavy, Guerry | Edland, Steven | Rogers, Whitney | Riley, David E. | Bordelon, Yvette | Standaert, David | Reich, Stephen G. | Litvan, Irene

Article Type: Research Article

Abstract: Background: PSP, like Alzheimer’s disease (AD), is a tauopathy. The etiopathogenesis of PSP is not well known and the role of stress has not yet been examined. Recent studies have shown that stress increases the risk for developing AD. This study investigates the role of stress as a risk factor for PSP. Objective: B To examine the association between the development of progressive supranuclear palsy (PSP) and self-reported life stressors. Methods: 76 patients diagnosed with PSP according to the NINDS-SPSP criteria and 68 age-matched unrelated controls were administered a life stressor questionnaire. Stress was quantified …as total number of events, number of life changing events, and number of events characterized by self-rated severity. Conditional odds ratio (OR) was calculated for each measure, with participants in the highest quartile of each measure being defined as high-exposure in relation to all other participants. Results: There were no significant differences between the reported number of total events or life-changing events in cases and controls. However, we found 24.4% of cases (N = 11) and 9.1% of controls (N = 5) had a higher exposure to high severity events, yielding an OR of 3.2 (p  = 0.04). Conclusions: We found that cases have over a three times greater odds of high exposure to high-severity events than controls prior to the clinical development of PSP, while there were no differences in overall number of reported events. Our findings suggest that high exposure to highly stressful events may be associated with the development of PSP. Show more

Keywords: Progressive supranuclear palsy (PSP), stress, epidemiology, case-control

DOI: 10.3233/JPD-160945

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 377-383, 2017

Authors: Brennan, Laura | Devlin, Kathryn M. | Xie, Sharon X. | Mechanic-Hamilton, Dawn | Tran, Baochan | Hurtig, Howard H. | Chen-Plotkin, Alice | Chahine, Lama M. | Morley, James F. | Duda, John E. | Roalf, David R. | Dahodwala, Nabila | Rick, Jacqueline | Trojanowski, John Q. | Moberg, Paul J. | Weintraub, Daniel

Article Type: Research Article

Abstract: Background: Methods to detect early cognitive decline and account for heterogeneity of deficits in Parkinson’s disease (PD) are needed. Quantitative methods such as latent class analysis (LCA) offer an objective approach to delineate discrete phenotypes of impairment. Objective: To identify discrete neurocognitive phenotypes in PD patients without dementia. Methods: LCA was applied to a battery of 8 neuropsychological measures to identify cognitive subtypes in a cohort of 199 non-demented PD patients. Two measures were analyzed from each of four domains: executive functioning, memory, visuospatial abilities, and language. Additional analyses compared groups on clinical characteristics and …cognitive diagnosis. Results: LCA identified 3 distinct groups of PD patients: an intact cognition group (54.8%), an amnestic group (32.2%), and a mixed impairment group with dysexecutive, visuospatial and lexical retrieval deficits (13.1%). The two impairment groups had significantly lower instrumental activities of daily living ratings and greater motor symptoms than the intact group. Of those diagnosed as cognitively normal according to MDS criteria, LCA classified 23.2% patients as amnestic and 9.9% as mixed cognitive impairment. Conclusions: Non-demented PD patients exhibit distinct neuropsychological profiles. One-third of patients with LCA-determined impairment were diagnosed as cognitively intact by expert consensus, indicating that classification using a statistical algorithm may improve detection of initial and subtle cognitive decline. This study also demonstrates that memory impairment is common in non-demented PD even when cognitive impairment is not clinically apparent. This study has implications for predicting eventual emergence of significant cognitive decline, and treatment trials for cognitive dysfunction in PD. Show more

Keywords: Parkinson’s disease, cognition, latent class analysis, neuropsychology

DOI: 10.3233/JPD-171081

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 385-395, 2017

Authors: Kader, Manzur | Ullén, Susann | Iwarsson, Susanne | Odin, Per | Nilsson, Maria H.

Article Type: Research Article

Abstract: Background: While walking difficulties are common in people with Parkinson’s disease (PD), little is known about factors that independently contribute to their perceived walking difficulties. Objective: To identify factors that independently contribute to perceived walking difficulties in people with PD. Methods: This study involved 243 (62% men) participants; their mean (min-max) age and PD duration were 70 (45–93) and 8 (1–43) years, respectively. A postal survey preceded a home visit that included observations, clinical tests, questions and questionnaires that were administered as a structured interview. Perceived walking difficulties (dependent variable) were assessed with the self-administered …generic Walk-12 (Walk-12G, scored 0–42, higher = worse). Independent variables included personal (e.g., age and general self-efficacy) and social environmental factors (e.g., social support and living situation) as well as disease-related factors including motor (e.g., freezing of gait (FOG) and postural instability) and non-motor symptoms (e.g., fatigue and orthostatic hypotension). Linear multiple regression analysis was used to identify factors that independently contributed to perceived walking difficulties. Results: Eight significant independent variables explained 56.3% of the variance in perceived walking difficulties. FOG was the strongest significant contributing factor to perceived walking difficulties, followed by general self-efficacy, fatigue, PD duration, lower extremity function, orthostatic hypotension, bradykinesia and postural instability. Conclusion : Motor and non-motor symptoms as well as personal factors (i.e., general self-efficacy) seem to be of importance for perceived walking difficulties in PD. These findings might nurture future interventions that address modifiable factors in order to enhance walking ability in people with PD. Show more

Keywords: Difficulty walking, fatigue, Parkinson Disease, patient outcome assessment, regression analysis, self-efficacy

DOI: 10.3233/JPD-161034

Citation: Journal of Parkinson's Disease, vol. 7, no. 2, pp. 397-407, 2017