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

Authors: Caviness, John N. | Hentz, Joseph G. | Belden, Christine M. | Shill, Holly A. | Driver-Dunckley, Erika D. | Sabbagh, Marwan N. | Powell, Jessica J. | Adler, Charles H.

Article Type: Research Article

Abstract: Background: QEEG could provide physiological biomarkers for changes over time in Parkinson's disease (PD) cognitive decline if they track with longitudinal neuropsychological performance. Objective: Our aim was to correlate longitudinal changes in frequency domain quantitative electroencephalography (QEEG) measures with change in neuropsychological performance testing in PD. Methods: 71 PD subjects, not demented at baseline, were studied from the Arizona Study of Aging and Neurodegenerative Disorders cohort. Baseline and follow-up digital EEG from PD subjects were analyzed for QEEG measures of background rhythm frequency and global relative power in delta (2.5–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), and beta (13–30 …Hz) bands. Baseline and subsequent evaluation included Mini Mental Status Examination and five other neuropsychological tests that load on cognitive domains known to decline in PD. Pearson coefficient was used to assess correlations. Multiple linear regression modeling was used to assess the effect of variable combinations of QEEG and other measures, including age and PD duration. Results: Changes in delta bandpower showed the highest and most consistent pattern of correlations with longitudinal changes in neuropsychological testing. The highest correlation was between delta bandpower increase and decline in the Rey Auditory-Verbal Learning Test (−0.59:p < 0.001). Delta bandpower was also increased in the incident dementia group compared to non-dementia at followup. Conclusions: 1) Longitudinal change in the QEEG frequency domain measure of delta bandpower correlated best with longitudinal neuropsychological performance change in PD; 2) These results constitute preliminary evidence that delta bandpower may be a suitable biomarker for evaluating PD cognitive deterioration longitudinally. Show more

Keywords: Parkinson's disease, dementia, electroencephalography, biological markers

DOI: 10.3233/JPD-140480

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 117-124, 2015

Authors: Lin, Tanya P. | Rigby, Heather | Adler, Jennifer S. | Hentz, Joseph G. | Balcer, Laura J. | Galetta, Steven L. | Devick, Steve | Cronin, Richard | Adler, Charles H.

Article Type: Research Article

Abstract: Background: Low-contrast vision is thought to be reduced in Parkinson's disease (PD). This may have a direct impact on quality of life such as driving, using tools, finding objects, and mobility in low-light condition. Low-contrast letter acuity testing has been successful in assessing low-contrast vision in multiple sclerosis. We report the use of a new iPad application to measure low-contrast acuity in patients with PD. Objective: To evaluate low- and high-contrast letter acuity in PD patients and controls using a variable contrast acuity eye chart developed for the Apple iPad. Methods: Thirty-two PD and 71 control subjects were studied. Subjects …viewed the Variable Contrast Acuity Chart on an iPad with both eyes open at two distances (40 cm and 2 m) and at high contrast (black and white visual acuity) and 2.5% low contrast. Acuity scores for the two groups were compared. Results: PD patients had significantly lower scores (indicating worse vision) for 2.5% low contrast at both distances and for high contrast at 2 m (p < 0.003) compared to controls. No significant difference was found between the two groups for high contrast at 40 cm (p = 0.12). Conclusions: Parkinson's disease patients have reduced low and high contrast acuity compared to controls. An iPad app, as used in this study, could serve as a quick screening tool to complement more formal testing of patients with PD and other neurologic disorders. Show more

Keywords: Parkinson's disease, vision, contrast sensitivity, visual acuity

DOI: 10.3233/JPD-140470

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 125-130, 2015

Authors: Duncan, Ryan P. | Leddy, Abigail L. | Cavanaugh, James T. | Dibble, Leland E. | Ellis, Terry D. | Ford, Matthew P. | Foreman, K. Bo | Earhart, Gammon M.

Article Type: Research Article

Abstract: Background: The natural progression of balance decline in individuals with Parkinson disease (PD) is not well understood. Objectives: We aimed to: 1) compare the utility of three standardized clinical measures for detecting balance decline over 1-year, 2) identify components of balance susceptible to decline, and 3) identify factors useful for predicting future balance decline. Methods: Eighty people with PD (59% male; mean age 68.2 ± 9.3; Hoehn & Yahr range I–IV) completed Balance Evaluation Systems Test (BESTest), Mini-BESTest, and Berg Balance Scale (BBS) assessments. Baseline predictor variables included the MDS-UPDRS III sub-score, presence of freezing, 6-month fall history, age, gender, …and physical activity. Balance and MDS-UPDRS III assessments were repeated at 6 (n = 51) and 12 months (n = 44). Results: BESTest and Mini-BESTest score declined over 6 and 12 months (P < 0.01). Postural responses, stability limits, and sensory orientation were most susceptible to decline. BBS score did not change (P > 0.01). MDS-UPDRS III score was unchanged over 6 months (P > 0.01), but declined over 12 months (P < 0.01). Change in BESTest score over 6 months was related to baseline MDS-UPDRS III, H&Y, freezing, and fall history (P < 0.05). Change in BESTest score over 12 months was related to baseline MDS-UPDRS III and freezing (P < 0.05). Change in Mini-BESTest over 12 months was related to baseline MDS-UPDRS III and age (P < 0.05). Conclusions: The BESTest and Mini-BESTest were responsive to balance decline in individuals with PD and helped to identify decline in underlying balance components. Disease severity and freezing most consistently predicted balance decline in persons with PD. Show more

Keywords: Parkinson disease, postural balance, outcome assessment, physical therapy, rehabilitation

DOI: 10.3233/JPD-140478

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 131-139, 2015

Authors: Sterling, Nicholas W. | Cusumano, Joseph P. | Shaham, Noam | Piazza, Stephen J. | Liu, Guodong | Kong, Lan | Du, Guangwei | Lewis, Mechelle M. | Huang, Xuemei

Article Type: Research Article

Abstract: Background: Reduced arm swing amplitude, symmetry, and coordination during gait have been reported in Parkinson's disease (PD), but the relationship between dopaminergic depletion and these upper limb gait changes remains unclear. Objective: We aimed to investigate the effects of dopaminergic drugs on arm swing velocity, symmetry, and coordination in PD. Methods: Forearm angular velocity was recorded in 16 PD and 17 control subjects (Controls) during free walking trials. Angular velocity amplitude of each arm, arm swing asymmetry, and maximum cross-correlation were compared between control and PD groups, and between OFF- and ON-medication states among PD subjects. Results: Compared to Controls, …PD subjects in the OFF-medication state exhibited lower angular velocity amplitude of the slower- (p = 0.0018), but not faster- (p = 0.2801) swinging arm. In addition, PD subjects demonstrated increased arm swing asymmetry (p = 0.0046) and lower maximum cross-correlation (p = 0.0026). Following dopaminergic treatment, angular velocity amplitude increased in the slower- (p = 0.0182), but not faster- (p = 0.2312) swinging arm among PD subjects. Furthermore, arm swing asymmetry decreased (p = 0.0386), whereas maximum cross-correlation showed no change (p = 0.7436). Pre-drug angular velocity amplitude of the slower-swinging arm was correlated inversely with the change in arm swing asymmetry (R = −0.73824, p = 0.0011). Conclusions: This study provides quantitative evidence that reduced arm swing and symmetry in PD can be modulated by dopaminergic replacement. The lack of modulations of bilateral arm coordination suggests that additional neurotransmitters may also be involved in arm swing changes in PD. Further studies are warranted to investigate the longitudinal trajectory of arm swing dynamics throughout PD progression. Show more

Keywords: Arm swing, dopamine, Parkinson's disease, locomotion, asymmetry, gait

DOI: 10.3233/JPD-140447

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 141-150, 2015

Authors: Tramontana, Michael G. | Molinari, Anna L. | Konrad, Peter E. | Davis, Thomas L. | Wylie, Scott A. | Neimat, Joseph S. | May, Alexandra T. | Phibbs, Fenna T. | Hedera, Peter | Gill, Chandler E. | Salomon, Ronald M. | Wang, Lily | Song, Yanna | Charles, David

Article Type: Research Article

Abstract: Background: Deep brain stimulation (DBS) is an effective treatment for patients with advanced Parkinson's disease (PD) and motor symptom complications. Recently, attention has been focused on whether offering DBS earlier in the course of PD is beneficial. Objective: The purpose of this study was to determine the effects of DBS on neuropsychological functioning in subjects with early stage PD. Methods: Thirty subjects with early PD (Hoehn & Yahr Stage II off medication) were randomized to optimal drug therapy (ODT) (n = 15) or bilateral subthalamic nucleus (STN) DBS+ODT (n = 15) after completing an expanded informed consent process specially designed …for the study and administered by a medical ethicist and the study team. Comprehensive neuropsychological testing was completed in the treatment-withdrawn state at baseline and at 12 month and 24 month follow-ups. Results: Two serious adverse events occurred in the DBS+ODT group. One subject experienced a stroke and another developed infected hardware that contributed to specific declines in cognitive functioning. However, compared to the ODT group, the remaining subjects in the DBS+ODT group exhibited modest reductions on a few measures of attention, executive function, and word fluency at 12 months. These differences were largely diminished at 24 months, especially when those with the adverse events were excluded. Conclusions: The results of this trial provide novel data regarding the effects of DBS on cognitive function in early PD. We believe that the findings and insights from this trial can help guide the safety analysis and risk-benefit evaluations in future discussions of DBS in early stage PD. Show more

Keywords: Parkinson's disease, deep brain stimulation, subthalamic nucleus, neuropsychological tests

DOI: 10.3233/JPD-140448

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 151-163, 2015

Authors: Slevin, John T. | Fernandez, Hubert H. | Zadikoff, Cindy | Hall, Coleen | Eaton, Susan | Dubow, Jordan | Chatamra, Krai | Benesh, Janet

Article Type: Research Article

Abstract: Background: Levodopa-carbidopa intestinal gel (LCIG) is delivered continuously via intrajejunal percutaneous gastrostomy tube. Objective: To examine long-term safety, efficacy and quality of life of LCIG in an open-label extension study. Methods: Patients received 52 weeks of open-label LCIG treatment following a 12-week double-blind, double-dummy trial in which they were randomized to either LCIG or immediate-release oral levodopa-carbidopa. Patient cohort designation was by receipt of LCIG in the preceding trial randomization (continuing-LCIG vs. LCIG-naïve patients). Results: Sixty-two of 66 subjects in the double-blind proceeded to the open-label extension. Most subjects (95%) reported ≥1 adverse event (AE); only 3 subjects (4.8%) discontinued …due to AEs. AE incidence declined gradually over 52 weeks. Serious AEs were reported by 23%. LCIG-naïve patients (N = 29) showed a decrease in “Off” time and an increase in “On” time without troublesome dyskinesia (change from baseline to final visit in mean [SD] hours = −2.34 [2.78] P < 0.001 and 2.19 [3.70] P = 0.005, respectively), while continuing-LCIG patients (N = 33) showed sustained “Off” time duration and further improvement in “On” time without troublesome dyskinesia (−0.42 [2.67] P = 0.377 and 1.00 [2.58] P = 0.036, respectively). The majority of patients in both groups (LCIG-naïve, continuing-LCIG, respectively) were rated ‘Much Improved’ or ‘Very Much Improved’ at final visit on the Clinical Global Impression-Improvement scale (69.0%, 69.7%). Conclusions: Continuing-LCIG patients continued to derive benefit from LCIG while the magnitude of improvement among LCIG-naïve patients was similar to that observed for patients on LCIG in the preceding double-blind study. The overall AE profile was consistent with previous phase 3 clinical trials involving the LCIG system. Show more

Keywords: Parkinson's disease, levodopa-carbidopa intestinal gel, motor fluctuations, percutaneous endoscopic gastrostomy, clinical trial

DOI: 10.3233/JPD-140456

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 165-174, 2015

Authors: Abbott, Sarah K. | Jenner, Andrew M. | Spiro, Adena S. | Batterham, Marijka | Halliday, Glenda M. | Garner, Brett

Article Type: Research Article

Abstract: Background: Oxidative stress contributes to Parkinson's disease (PD) etiology. Although previous studies have focused on sources of free radical formation in brain regions affected by PD, less is known regarding changes in lipid composition and the implications for susceptibility to peroxidation. Objective: To assess fatty acid profiles from control and PD tissues that are susceptible to PD pathology but devoid of severe destruction. Methods: We used gas chromatography methods to assess fatty acid profiles from control (n = 10) and PD (n = 9) postmortem tissues. We focused on the anterior cingulate cortex (ACC), a region that accumulates alpha-synuclein, but …does not undergo severe destruction, and compared this to the occipital cortex, a region that is pathologically spared. Results: Our data indicate a significant 33% increase in the proportion of polyunsaturated fatty acids (mol%) present in the PD ACC as compared to control ACC. Increases in highly unsaturated 22:5n-6 and 22:6n-3 fatty acids were particularly pronounced (109% and 73%, respectively). Calculation of a peroxidation index (accounting for total fatty acyl double bounds) indicated a 44% increase in susceptibility of the PD ACC to lipid peroxidation compared to control ACC. Such differences were not detected in the occipital cortex from the same donors. Assessment of F2 -isprostane levels confirmed that PD tissue lipids were more oxidized than controls. Conclusions: The global composition of fatty acids in the PD ACC is altered in a way that increases susceptibility to peroxidation in a region-specific manner. This has important implications for PD, supporting the oxidative stress hypothesis of PD pathogenesis. Show more

Keywords: Parkinson's disease, fatty acids, lipid peroxidation, F2-isoprostanes, oxidative stress, postmortem tissue analysis

DOI: 10.3233/JPD-140479

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 175-185, 2015

Authors: Serrano, J. Artur | Larsen, Frank | Isaacs, Tom | Matthews, Helen | Duffen, Joy | Riggare, Sara | Capitanio, Fulvio | Ferreira, Joaquim J. | Domingos, Josefa | Maetzler, Walter | Graessner, Holm | SENSE-PARK Consortium

Article Type: Research Article

Abstract: Background: There is a growing interest in the objective assessment of health related outcomes using technology providing quality measurements to be applied not only in daily clinical practice, but also in scientific research. Differences in the understandings of the condition and the terminology used between people with Parkinson's (PwPs), clinicians and technical developers may influence the progress of a participatory design process. Objective: This paper reports on a participatory design process to achieve a consensus among PwPs, clinicians and technologists over the selection of a set of symptomatic domains to be continuously assessed, in order to provide results relevant to …both PwPs and clinicians. Methods: The methods used were a Web based user survey, end-user focus groups, ranking by combined methods, a Delphi process performed among clinicians and scientists, and prioritization of the results in a concertation workshop for PwPs, clinicians and technologists. Results: The following symptomatic domains were commonly agreed by PwPs and clinicians to be of central importance in a system of continuous assessment: hypokinesia/bradykinesia, tremor, sway, gait, sleep and cognition. This list satisfied both the needs of the PwPs and the concerns of the clinicians regarding the means of advancing new strategies in assessment and interventions in PD. Conclusions: A participatory design strategy allowed the definition of a consensual list of symptomatic domains. Both the strategy and the achieved results may be of relevance for similar interdisciplinary approaches in the field of PD using a participatory design involving patients, clinicians and technologists. Show more

Keywords: Parkinson's Disease (PD), People with Parkinson's (PwPs), participatory design, assessment strategies, biomarkers, chronic disease management, combined methods, degenerative disease, diagnostic markers, focus group, symptomatic domain, monitoring

DOI: 10.3233/JPD-140472

Citation: Journal of Parkinson's Disease, vol. 5, no. 1, pp. 187-196, 2015