Journal of Parkinson's Disease - Volume 5, issue 1

Authors: Allen Reish, Heather E. | Standaert, David G.

Article Type: Review Article

Abstract: Alpha-synuclein (α-syn) is central to the pathogenesis of Parkinson disease (PD). Gene duplications, triplications and point mutations in SNCA1, the gene encoding α-syn, cause autosomal dominant forms of PD. Aggregated and post-translationally modified forms of α-syn are present in Lewy bodies and Lewy neurites in both sporadic and familial PD, and recent work has emphasized the prion-like ability of aggregated α-syn to produce spreading pathology. Accumulation of abnormal forms of α-syn is a trigger for PD, but recent evidence suggests that much of the downstream neurodegeneration may result from inflammatory responses. Components of both the innate and adaptive immune systems …are activated in PD, and influencing interactions between innate and adaptive immune components has been shown to modify the pathological process in animal models of PD. Understanding the relationship between α-syn and subsequent inflammation may reveal novel targets for neuroprotective interventions. In this review, we examine the role of α-syn and modified forms of this protein in the initiation of innate and adaptive immune responses. Show more

Keywords: Parkinson disease, alpha-synuclein, post-translational modifications, microglia, T-lymphocyte, innate immunity, adaptive immunity, antigen presentation

DOI: 10.3233/JPD-140491

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 1-19, 2015

Authors: Lamotte, Guillaume | Rafferty, Miriam R. | Prodoehl, Janey | Kohrt, Wendy M. | Comella, Cynthia L. | Simuni, Tanya | Corcos, Daniel M.

Article Type: Review Article

Abstract: Background: Despite the benefits of medications and surgical interventions for Parkinson's disease (PD), these treatments are not without complications and neuroprotective strategies are still lacking. Therefore, there is a need for effective alternative approaches to treat motor and non-motor symptoms in PD. During the last decade, several studies have investigated endurance exercise training as a potential treatment for individuals with PD. Objective: This paper reviews the therapeutically beneficial effects of endurance exercise training on motor and non-motor symptoms in PD. Methods: First, we performed a systematic review of the literature on the effects of endurance exercise training on motor and …non-motor signs of parkinsonism, functional outcomes including gait, balance and mobility, depression and fatigue, quality of life and perceived patient improvement, cardiorespiratory function, neurophysiological measures, and motor control measures in PD. Second we performed a meta-analysis on the motor section of the UPDRS. Then, we focused on several important factors to consider when prescribing endurance exercise training in PD such as intensity, duration, frequency, specificity and type of exercise. In addition, we identified current knowledge gaps regarding endurance exercise training in PD and made suggestions for future research. Results: A total of eight randomized controlled trials met the inclusion criteria and were reviewed. This systematic review synthesizes evidence that endurance exercise training at a sufficiently high level enhances cardiorespiratory capacity and endurance by improving VO2 max and gait in moderately to mildly affected individuals with PD. However, there is not yet a proven effect of endurance exercise training on specific features of PD such as motor signs of parkinsonism. Conclusion: Endurance exercise training improves physical conditioning in PD patients; however, to date, there is insufficient evidence to include endurance exercise training as a specific treatment for PD. There is a need for well-designed large-scale randomized controlled trials to confirm benefits and safety of endurance exercise training in PD and to explore potential benefits on the motor and non-motor signs of PD. Show more

Keywords: Parkinson's disease, endurance, exercise, aerobic exercise, motor activity, gait, balance

DOI: 10.3233/JPD-140425

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 21-41, 2015

Authors: Nonnekes, Jorik | Goselink, Rianne | Weerdesteyn, Vivian | Bloem, Bastiaan R.

Article Type: Research Article

Abstract: Postural instability is a disabling feature of Parkinson's disease (PD), contributing to recurrent falls and fall-related injuries. The retropulsion test is widely regarded as the gold standard to evaluate postural instability, and is therefore a key component of the neurological examination in PD. Many variants exist, which confuses both clinical practice and research. Here, we evaluate the merits of this test by discussing three common variants: (1) the pull test as described in the MDS-UPDRS scale; (2) using an unexpected shoulder pull, without prior warning; and (3) the push-and-release test. All variants are a quick method to index the degree …of postural instability, but the outcome can vary considerably due to variability in test execution and -interpretation. This partially explains why the retropulsion test fails to predict future falls in PD. Another explanation is that falling results from the complex interplay between gait, balance, cognitive decline and environmental factors, and the retropulsion test captures only part of that. We conclude with several recommendations for current clinical practice. Show more

Keywords: Parkinson's disease, postural control, postural instability, retropulsion test, falls

DOI: 10.3233/JPD-140514

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 43-47, 2015

Authors: Scullin, Michael K. | Fairley, Jacqueline A. | Trotti, Lynn Marie | Goldstein, Felicia C. | Factor, Stewart A. | Bliwise, Donald L.

Article Type: Short Communication

Abstract: Background: Sleep disturbance and cognitive impairment are correlated in non-diseased populations, but their association in Parkinson's disease (PD) is uncertain. Prior studies examining measures of cognition in relation to sleep have used either self-report or actigraphically measured sleep and have produced conflicting findings. Objective: In this descriptive study, we correlated measurements of sleep in PD patients derived from the gold-standard measurement, in-lab polysomnography, with an extensive battery of cognitive measures. We hypothesized that poorer sleep would be related to relatively more impaired cognition. Methods: Idiopathic PD patients (n = 34) completed a cognitive battery encompassing three broad domains (executive function, …immediate memory and delayed memory), and underwent PSG for two nights. Scores for each domain from individual cognitive measures were converted to z-scores and then averaged to produce a composite score. We used second night PSG data and quantified measures of sleep architecture, sleep continuity, sleep apnea and nocturnal movement (periodic leg movements, PLMS). Results: Lower executive function was associated with higher PLMS after controlling for chronological age, mini-mental state examination scores, and UPDRS motor subscale scores. These results were independent from psychomotor speed. There was a marginally significant positive correlation between the proportion of time spent in REM and immediate recall ability. Measures of sleep continuity and sleep apnea were unrelated to cognition in these patients. Conclusions: PLMS, known to be a frequent feature of PSG-measured sleep in PD, may be an important correlate of impaired executive function in PD. Whether treating this disorder of sleep results in improvement in cognition remains to be determined. Show more

Keywords: Sleep related periodic leg movements, sleep fragmentation, sleep disorders, neurodegenerative diseases, cognition, aging

DOI: 10.3233/JPD-140475

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 49-54, 2015

Authors: Rocker, Charlotte | Cappelletti, Lily | Marshall, Claudia | Meunier, Claire C. | Brooks, Deborah W. | Sherer, Todd | Chowdhury, Sohini

Article Type: Research Article

Abstract: Background: As in other therapeutic areas, clinical studies in Parkinson's disease (PD) face significant recruitment challenges. However, qualitative surveys suggest that individuals with PD are willing to participate in clinical research. The Michael J. Fox Foundation therefore established Fox Trial Finder in 2011 to facilitate connection between PD research teams and volunteers. Objective: Characterize the research volunteers (with and without PD) registered on Fox Trial Finder as of June 2014, and the published, recruiting studies to identify trends and highlight gaps between research requirements and available volunteers. Methods: Profiles of volunteers with and without PD were analyzed to explore trends …in geography, demographics, family history and, for those volunteers with PD, disease progression and treatment history. Clinical study profiles were analyzed to determine study type, phase, sponsor, focus, location and eligibility criteria. The analysis focused on volunteers and studies based in the United States. Results: The database contained 26,261 US-based volunteers, including 19,243 volunteers (73%) with PD and 7,018 (27%) controls without PD. The average time since diagnosis for PD volunteers was 5.7 years and the average age at diagnosis was 58 years. Control volunteers were more likely than volunteers with PD to be female (67% vs. 35%) and to have a family history of PD (49% vs. 12%). Conclusions: Fox Trial Finder's registration history to date demonstrates the high level of willingness among individuals affected by PD to participate in clinical research and provide a significant amount of personal health information to facilitate that participation. Show more

Keywords: Parkinson's disease, patient recruitment, research subject recruitment, clinical trial, observational study

DOI: 10.3233/JPD-140522

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 55-66, 2015

Authors: Parashos, Sotirios A. | Elm, Jordan | Boyd, James T. | Chou, Kelvin L. | Dai, Lin | Mari, Zoltan | Morgan, John C. | Sudarsky, Lewis | Wielinski, Catherine L.

Article Type: Research Article

Abstract: Background: A construct calculated as the sum of items 13–15, 29, 30 of the Unified Parkinson's Disease Rating Scale (UPDRS) has been used as an “Ambulatory Capacity Measure” (ACM) in Parkinson disease (PD). Its construct validity has never been examined. A similar construct, consisting of the mean value of the same UPDRS items has been used under the acronym PIGD as a measure of postural instability and gait disorder in PD. Objective: To examine the construct validity of the ACM and PIGD in PD. Methods: We analyzed data in an existing database of 340 PD patients, Hoehn and Yahr stages …(HYS) 1–5 who participated in a study of falls. Number of falls (NOF) was recorded over 4 weeks, and UPDRS (mental, ADL, and motor subscales), HYS, Activities Based Confidence Scale (ABC), Freezing of Gait Questionnaire (FOG), Five Times Sit-to-Stand (FTSS), Timed Up-and Go (TUG), Gait Velocity (GV), and Berg Balance Scale (BBS) evaluations were performed. Internal consistency was assessed by Cronbach's alpha. Construct validity was assessed through correlations of the ACM and PIGD to these measures and to their summed-ranks. A coefficient of determination was calculated through linear regression. Results: Mean age was 71.4, mean age at diagnosis 61.4 years; 46% were women; mean UPDRS subscale scores were: Mental 3.7; ADL 15.7; motor: 27.1; mean ACM was 6.51, and mean PIGD 1.30. Cronbach's alpha was 0.78 for both ACM and PIGD. Spearman correlation coefficients between the ACM/PIGD and ABC, FOG, TUG, GV and BBS were 0.69, 0.72, 0.67, 0.58, and 0.70 respectively. Correlation between the ACM/PIGD and summed-ranks of HYS, NOF, ABC, FOG, FTSS, TUG, GV and BBS was high (Spearman r = 0.823, p < 0.0001); 68% of the variability in the summed-ranks was explained by ACM/PIGD. Conclusion: The ACM and the PIGD are valid global measures and accurately reflect the combined effects of the various components of ambulatory capacity in PD patients with HY stages 1–4. Show more

Keywords: Idiopathic Parkinson disease, ambulation, scales, balance, falls, PIGD, ambulatory capacity

DOI: 10.3233/JPD-140405

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 67-73, 2015

Authors: Seichepine, Daniel R. | Neargarder, Sandy | Davidsdottir, Sigurros | Reynolds, Gretchen O. | Cronin-Golomb, Alice

Article Type: Research Article

Abstract: Background/Objectives: Visuospatial problems are common in Parkinson's disease (PD) and likely stem from dysfunction in dopaminergic pathways and consequent disruption of cortical functioning. Characterizing the motor symptoms at disease onset provides a method of observing how dysfunction in these pathways influences visuospatial cognition. We examined two types of motor characteristics: Body side (left or right) and type of initial symptom (tremor or symptom other than tremor). Methods: 31 non-demented patients with PD, 16 with left-side onset (LPD) and 15 with right-side onset (RPD), as well as 17 healthy control participants (HC). The PD group was also divided by type of …initial motor symptom, 15 having tremor as the initial symptom and 16 having an initial symptom other than tremor. Visuospatial function was assessed with the Clock Drawing Test. Results: Of the four Clock Drawing scoring methods used, the Rouleau method showed sensitivity to subgroup differences. As predicted, the LPD and non-tremor subgroups, but not the other subgroups, performed more poorly than the HC group. Conclusion: The findings provide further evidence for differences in cognition between these subtypes of PD and highlight the importance of considering disease subtypes when examining cognition. Show more

Keywords: Functional laterality, parkinsonian, spatial behavior, cognition, neuropsychology

DOI: 10.3233/JPD-140365

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 75-83, 2015

Authors: Daneault, Jean-François | Sadikot, Abbas F. | Barbat-Artigas, Sébastien | Aubertin-Leheudre, Mylène | Jodoin, Nicolas | Panisset, Michel | Duval, Christian

Article Type: Research Article

Abstract: Background: Maintaining a physically active lifestyle promotes general health. Recent studies have demonstrated that patients with Parkinson's disease (PD) fail to meet the suggested levels of physical activity and that targeted interventions do not always improve this behavior. One validated treatment for motor symptoms in PD is subthalamic stimulation (STN DBS). Objective: Assess whether motor symptom improvement following STN DBS translated into increased physical activity behavior. Methods: Twenty patients with PD scheduled for bilateral STN DBS filled-out the Phone-FITT physical activity questionnaire and the SF-36 quality of life questionnaire prior to surgery and 6 to 9 months postoperatively. Data were …compared to age- and gender-matched healthy controls. Results: Our results demonstrate that PD patients' quality of life is significantly lower than healthy controls. While STN DBS improves motor symptoms in the intermediate term, it only improves some aspects of quality of life related to physical function. Furthermore, STN DBS does not modify physical activity behavior measured by the Phone-FITT, whether for household or recreational activities. Conclusion: The current study demonstrates that the motor improvements observed after STN DBS do not lead to systematic improvements in all aspects of quality of life or increased levels of physical activity. This highlights the need to develop and implement intervention strategies to promote an active lifestyle in this population, even if clinical improvement is evident following surgery. Show more

Keywords: Parkinson, STN, DBS, quality of life, exercise

DOI: 10.3233/JPD-140426

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 85-93, 2015

Authors: Le Goff, Floriane | Derrey, Stéphane | Lefaucheur, Romain | Borden, Alaina | Fetter, Damien | Jan, Maryvonne | Wallon, David | Maltête, David

Article Type: Research Article

Abstract: Background: Decline in verbal fluency (VF) is frequently reported after chronic deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson disease (PD). Objective: We investigated whether the trajectory of the implanted electrode correlate with the VF decline 6 months after surgery. Methods: We retrospectively analysed 59 PD patients (mean age, 61.9 ± 7; mean disease duration, 13 ± 4.6) who underwent bilateral STN-DBS. The percentage of VF decline 6 months after STN-DBS in the on-drug/on-stimulation condition was determined in respect of the preoperative on-drug condition. The patients were categorised into two groups (decline and stable) for each VF. …Cortical entry angles, intersection with deep grey nuclei (caudate, thalamic or pallidum), and anatomical extent of the STN affected by the electrode pathway, were compared between groups. Results: A significant decline of both semantic and phonemic VF was found after surgery, respectively 14.9% ± 22.1 (P < 0.05) and 14.2% ± 30.3 (P < 0.05). Patients who declined in semantic VF (n = 44) had a left trajectory with a more anterior cortical entry point (56 ± 53 versus 60 ± 55 degree, P = 0.01) passing less frequently trough the thalamus (P = 0.03). Conclusions: Microlesion of left brain regions may contribute to subtle cognitive impairment following STN-DBS in PD. Show more

Keywords: Verbal fluency, deep brain stimulation, subthalamic nucleus, parkinson's disease, microlesion

DOI: 10.3233/JPD-140443

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 95-104, 2015

Authors: Brodie, Matthew A.D. | Dean, Roger T. | Beijer, Tim R. | Canning, Colleen G. | Smith, Stuart T. | Menant, Jasmine C. | Lord, Stephen R.

Article Type: Research Article

Abstract: Background: Unsteady gait and falls are major problems for people with Parkinson's disease (PD). Symmetric auditory cues at altered cadences have been used to improve walking speed or step length. However, few people are exactly symmetric in terms of morphology or movement patterns and effects of symmetric cueing on gait steadiness are inconclusive. Objectives: To investigate if matching auditory cue a/symmetry to an individual's intrinsic symmetry or asymmetry affects gait steadiness, gait symmetry, and comfort to cues, in people with PD, healthy age-matched controls (HAM) and young. Methods: Thirty participants; 10 with PD, 11 HAM (66 years), and 9 young …(30 years), completed five baseline walks (no cues) and twenty-five cued walks at habitual cadence but different a/symmetries. Outcomes included; gait steadiness (step time variability and smoothness by harmonic ratios), walking speed, symmetry, comfort, and cue lag times. Results: Without cues, PD participants had slower and less steady gait than HAM or young. Gait symmetry was distinct from gait steadiness, and unaffected by cue symmetry or a diagnosis of PD, but associated with aging. All participants maintained preferred gait symmetry and lag times independent of cue symmetry. When cues were matched to the individual's habitual gait symmetry and cadence: Gait steadiness improved in the PD group, but deteriorated in the HAM controls, and was unchanged in the young. Gait outcomes worsened for the two PD participants who reported discomfort to cued walking and had high New Freezing of Gait scores. Conclusions: It cannot be assumed all individuals benefit equally from auditory cues. Symmetry matched auditory cues compensated for unsteady gait in most people with PD, but interfered with gait steadiness in older people without basal ganglia deficits. Show more

Keywords: Auditory cues, Parkinson's disease, gait steadiness, symmetry, asymmetry

DOI: 10.3233/JPD-140430

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 105-116, 2015