Moderate Stage Parkinson's Disease Research Articles

Mediolateral Postural Control during Gait in Parkinson's Disease.

ABSTRACTObjectives:Balance in the mediolateral direction is usually maintained in patients with early-stage Parkinson’s disease (PD), but not in moderate-stage PD as revealed by the Tandem Gait Test. Although mediolateral postural control in PD patients remains controversial, previous studies have shown that the Tandem Gait Test may predict the risk of future falls in patients with PD. This study aimed to clarify postural control differences among PD patients with and without mediolateral balance impairments (MLBI: mediolateral balance impairments, nMLBI: non-mediolateral balance impairments, respectively) and healthy controls (HCs).Methods:We recruited 40 PD patients and 20 HCs. According to the Tandem Gait Test score, PD patients were divided into MLBI and nMLBI groups. Primary outcome measures were the ambulatory movement trajectory amplitude of the center of mass and its coefficient of variation (CV) during gait.Results:Mediolateral movement trajectory amplitudes and CV were not significantly different between the nMLBI group and HCs, whereas the mediolateral movement trajectory amplitude in the MLBI group was significantly higher than that in the nMLBI group. Moreover, the CV of the mediolateral movement trajectory amplitude in the MLBI group was significantly lower than that in the nMLBI group. The mediolateral movement trajectory amplitude was significantly correlated with the fall score.Conclusions:The current results suggest that PD patients with mediolateral balance impairments showed mediolateral postural sway during gait compared with PD patients without mediolateral balance impairments. It is necessary to focus on the instabilities in the mediolateral direction to avoid falls in PD patients.

Brain Functional and Structural Signatures in Parkinson's Disease.

The aim of this study is to explore functional and structural properties of abnormal brain networks associated with Parkinson’s disease (PD). 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG PET) and T1-weighted magnetic resonance imaging from 20 patients with moderate-stage PD and 20 age-matched healthy controls were acquired to identify disease-related patterns in functional and structural networks. Dual-modal images from another prospective subject of 15 PD patients were used as the validation group. Scaled Subprofile Modeling based on principal component analysis method was applied to determine disease-related patterns in both modalities, and brain connectome analysis based on graph theory was applied to verify these patterns. The results showed that the expressions of the metabolic and structural patterns in PD patients were significantly higher than healthy controls (PD1-HC, p = 0.0039, p = 0.0058; PD2-HC, p < 0.001, p = 0.044). The metabolic pattern was characterized by relative increased metabolic activity in pallidothalamic, pons, putamen, and cerebellum, associated with metabolic decreased in parietal–occipital areas. The structural pattern was characterized by relative decreased gray matter (GM) volume in pons, transverse temporal gyrus, left cuneus, right superior occipital gyrus, and right superior parietal lobule, associated with preservation in GM volume in pallidum and putamen. In addition, both patterns were verified in the connectome analysis. The findings suggest that significant overlaps between metabolic and structural patterns provide new evidence for elucidating the neuropathological mechanisms of PD.

Substantia nigra locations of iron-content, free-water and mean diffusivity abnormalities in moderate stage Parkinson's disease

BackgroundPrior work demonstrated that free water in the posterior substantia nigra (SN) was elevated in Parkinson's disease (PD) compared to healthy controls (HC) across single- and multi-site cohorts, and increased over 1 year in Parkinson's disease but not in relation with the iron deposition in SN with the relaxometry T2*. ObjectivesThe main objective of the present study was to evaluate changes in the SN using relaxometry T2*, single- and bi-tensor models of diffusion magnetic resonance imaging between PD patients and HC. Methods39 subjects participated in this study, including 21 HCs and 18 PD patients, in moderate stage (7 years), whose data were collected at two visits separated by approximately 2 years, underwent 3-T MRI comprising: T2*-weighted, T1-weighted and diffusion tensor imaging (DTI) scans. Relaxometry T2*, bi-tensor free water (FW), free-water-corrected fractional anisotropy, free-water-corrected mean diffusivity, single-tensor fractional anisotropy, and single-tensor mean diffusivity were computed for the anterior, posterior and whole substantia nigra. ResultsIn the anterior SN, relaxometry T2* values were greater for PD patients than HCs. In the posterior SN, free water, single- and bi-tensor mean diffusivity values were greater for PD patients than HCs. No significant change were found over time in FW/MD/R2* maps for PD patients with moderate stage. ConclusionThe specific increase of R2* in the anterior SN concomitant with the specific increase of FW in posterior SN suggests a complementary aspect of the two parameters and, perhaps, different underlying pathophysiological processes.

What Effects Might Exenatide have on Non-Motor Symptoms in Parkinson's Disease: A Post Hoc Analysis.

Exenatide is a GLP-1 receptor agonist that was recently studied for potential disease-modifying effects in a randomised, placebo-controlled clinical trial in patients with moderate stage Parkinson's disease, and showed positive effects on the motor severity of the disease which were sustained 12 weeks beyond the period of exenatide exposure. Analysis of pre-defined secondary outcomes revealed no statistically significant differences between patients treated with exenatide in total non-motor symptom burden and overall quality of life measures. The response of individual non-motor symptoms to an intervention may vary and thus this post hoc analysis was conducted to explore the possible effects of exenatide compared to placebo on individual non-motor symptoms. Compared to placebo, patients treated with exenatide-once weekly had greater improvements in individual domains assessing mood/depression across all observer-rated outcome measures after 48 weeks including the "mood/apathy" domain of the NMSS, - 3.3 points (95% CI - 6.2, - 0.4), p = 0.026; the "mood" score (Q1.3+Q1.4 of the MDS-UPDRS Part 1), - 0.3 points (95% CI - 0.6, - 0.1), p = 0.034; and a trend in the MADRS total score, - 1.7 points (95% CI - 3.6, 0.2), p = 0.071. In addition, there was an improvement in the "emotional well-being" domain of the PDQ-39 of 5.7 points ((95% CI - 11.3, - 0.1), p = 0.047 though these improvements were not sustained 12 weeks after exenatide withdrawal. At 48 weeks these changes were of a magnitude that would be subjectively meaningful to patients and were not associated with changes in motor severity or other factors, suggesting exenatide may exert independent effects on mood dysfunction. These exploratory findings will contribute to the design of future trials to confirm the extent of motor and non-motor symptom effects of exenatide in larger cohorts of patients.

Is Exenatide a Treatment for Parkinson's Disease?

There is growing interest in the use of glucagon-like peptide-1 agonists as treatments for Parkinson's disease following the recent publication of the results of the Exenatide-PD trial. In this randomized, double-blind, placebo controlled trial, patients with moderate stage Parkinson's disease treated with once-weekly subcutaneous injections of exenatide 2 mg (Bydureon) for 48 weeks, had a 3.5-point advantage over the placebo group in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor subscale (Part 3) in the practically defined OFF medication state, 12 weeks after cessation of the trial drug. In this article, we discuss some of the important issues of relevance to this trial, with regards to trial design, patient selection, choice of outcome measure and also place into context the implications these results have for patients with Parkinson's disease and the wider research community.

Land Plus Aquatic Therapy Versus Land-Based Rehabilitation Alone for the Treatment of Balance Dysfunction in Parkinson Disease: A Randomized Controlled Study With 6-Month Follow-Up

ObjectivesTo assess whether a specific land-based physical intervention with the inclusion of aquatic therapy is more effective than land-based rehabilitation alone for the treatment of balance dysfunction in patients with Parkinson disease (PD), immediately after therapy and at 6 months' follow-up. DesignRandomized controlled study with 6-month follow-up. SettingA PD and brain injury rehabilitation department in a general hospital. ParticipantsPatients (N=34) with moderate-stage PD. InterventionSeventeen patients underwent a land-based rehabilitation protocol called multidisciplinary intensive rehabilitation treatment (MIRT), and 17 underwent MIRT plus aquatic therapy (MIRT-AT). Main Outcome MeasuresThe primary outcome measure was the Berg Balance Scale (BBS); secondary outcome measures were the Unified Parkinson Disease Rating Scale parts II and III (UPDRS II/III) and the Timed Up and Go (TUG) test. These measures were assessed in both groups at admission, at discharge, and after 6 months. ResultsBBS improved after treatment in both groups. Even though no statistically significant difference between groups was observed at each observation time, BBS scores at follow-up were significantly higher than at baseline in MIRT-AT patients. Both groups also showed an improvement in UPDRS II/III and TUG at the end of treatment compared with baseline, but these findings were lost at the 6-month follow-up. ConclusionsAquatic therapy added to land-based rehabilitation could provide a contribution to the treatment of balance dysfunction in patients with moderate-stage PD.

The relationship between balance confidence and control in individuals with Parkinson's disease

IntroductionA broad range of subjective and objective assessments have been used to assess balance confidence and balance control in persons with Parkinson's disease (PD). However, little is known about the relationship between self-perceived balance confidence and actual balance control in PD. The purpose of this investigation was to determine the relationship between self-perceived balance confidence and objectively measured static/dynamic balance control abilities. MethodsForty-four individuals with PD participated in the study. Patients were stratified into 2 groups based on the modified Hoehn and Yahr (H&Y) disability score: early stage, H&Y ≤ 2.0 and moderate stage, H&Y ≥ 2.5. All participants completed the activities-specific balance confidence (ABC) scale and performed standing balance and gait initiation tasks to assess static and dynamic balance control. The center of pressure (COP) sway (CE95%Sway) during static balance and the peak distance between the projections of the COP and the center of mass (COM) in the transverse plane (COPCOM) during gait initiation were calculated. Pearson correlation analyses were conducted relating the ABC score and CE95%Sway and COPCOM. ResultsFor early stage PD, there was a moderate correlation between ABC score and CE95%Sway (r = −0.56, R2 = 0.32, p = 0.002), while no significant correlation was found between ABC score and COPCOM (r = −0.24, R2 = 0.06, p = 0.227). For moderate stage PD, there was a moderate correlation between ABC score and COPCOM (r = 0.49, R2 = 0.24, p = 0.044), while no correlation was found between ABC score and CE95%Sway (r = −0.19, R2 = 0.04, p = 0.478). ConclusionIndividuals with different disease severities showed different relationships between balance confidence and actual static/dynamic balance control.

Effects of a guided self-rehabilitation contract in patients with moderate stage Parkinson's disease

This study compared two different applications of Guided Self-rehabilitation Contracts (GSC) in Parkinson's disease, individual (I) or group-wise (C), in a 3-month intensive training focused on balance. Fourteen patients were randomized into 2 parallel groups (I and C) with one physical therapy session every 10 days for 3 months. Each session associated education and exercise prescription that each patient had to perform daily between sessions. Each patient was to complete a log recording daily work and wear a pedometer. Evaluations, OFF and ON, included Global Mobility Task (GMT), UPDRS III, proof of effort, 20-m walk test, 2-minute endurance test and Functional Reach Test (FRT). Results of the two groups were similar. Patients worked alone about 40 minutes a day, 6 days per week. Improvements involved the daily number of steps (+19.2%, P = 0.091), UPDRS III-OFF (–30.1%, P = 0.029), GMT-ON (–11.2%, P = 0.042) and stride length at comfortable speed (+9.6%, P = 0.029). An intensive rehabilitation program in the form of a GSC is feasible in Parkinson's disease, either individually or collectively; it seems to reduce parkinsonian symptoms and to bring functional benefits.

Parkinson's disease-related spatial covariance pattern identified with resting-state functional MRI.

In this study, we sought to identify a disease-related spatial covariance pattern of spontaneous neural activity in Parkinson's disease using resting-state functional magnetic resonance imaging (MRI). Time-series data were acquired in 58 patients with early to moderate stage Parkinson's disease and 54 healthy controls, and analyzed by Scaled Subprofile Model Principal Component Analysis toolbox. A split-sample analysis was also performed in a derivation sample of 28 patients and 28 control subjects and validated in a prospective testing sample of 30 patients and 26 control subjects. The topographic pattern of neural activity in Parkinson's disease was characterized by decreased activity in the striatum, supplementary motor area, middle frontal gyrus, and occipital cortex, and increased activity in the thalamus, cerebellum, precuneus, superior parietal lobule, and temporal cortex. Pattern expression was elevated in the patients compared with the controls, with a high accuracy (90%) to discriminate the patients from the controls. The split-sample analysis produced a similar pattern but with a lower accuracy for group discrimination in both the derivation (80%) and the validation (73%) samples. Our results showed that resting-state functional MRI can be potentially useful for identification of Parkinson's disease-related spatial covariance patterns, and for differentiation of Parkinson's disease patients from healthy controls at an individual level.

Development and evaluation of a dyadic intervention for elderly couples living with moderate-stage Parkinson disease

PurposeThe purpose of this qualitative study was to develop, test and evaluate a dyadic intervention for elderly couples living with moderate-stage Parkinson disease. MethodsBased on Meleis's theory of transitions and following systemic and participatory approaches, the study comprised four steps informed by the intervention mapping process: 1) assessing couples' intervention needs, preferences and objectives; 2) developing and validating a dyadic intervention proposal; 3) formalizing the dyadic intervention; and 4) testing and evaluating the dyadic intervention. ResultsThe dyadic intervention consisted of seven 90-minutes sessions held every other week. Intervention content and strategies used were based on couples' needs, preferences and objectives, as well as specific theories, models and empirical findings. ConclusionThis study can assist nurses involved in different domains of practice and interested in developing and evaluating theoretically based dyadic interventions.

A-31 * The Effects of Rasagiline on Cognition in Mild to Moderate Stage Parkinson's Disease, A Double-Blind Placebo Controlled Study

Objective: Cognitive deficits can occur even in the early stages of Parkinson's disease (PD) and are often subtle, but discernible with neuropsychological testing, and are progressive. Rasagiline, an MAO-B inhibitor, has recently shown benefits consistent with a possible disease modifying effect. We hypothesized that rasagiline would slow the decline of cognition in non-demented patients with mild to moderate PD. Method: 50 participants recruited from a Movement Disorders Clinic with mild to moderate PD, Mini Mental Status (MMSE) scores greater than 23/30, and without depression participated in a 6 month, double blind, placebo controlled trial with rasagiline. Participants were not randomized on other PD medication use and PD medication use remained stable over the course of the trial. Participants completed a battery of neuropsychological tests assessing a range of cognitive domains both at baseline and after 6 months of receiving 1 mg of rasagiline or placebo daily. 23 rasagiline and 22 control participants completed the study. Results: Independent t-tests found our two groups to be equivalent in age, motor impairment, gender, PD medication status, and MMSE score. Repeated measures ANOVA comparing pre- and post-treatment scores on tests of attention, executive functioning, visuospatial and language abilities, and memory failed to find significant differences between the rasagiline and control groups. Conclusion(s): Use of rasagiline was not found to positively impact cognitive functioning in this study of non-demented, mild to moderate stage PD patients. Future research may exam the potential effects of rasagiline on cognition over a greater period of time and could involve individuals with demonstrable mild cognitive impairments.

Randomized trial of cognitive speed of processing training in Parkinson disease

To examine the efficacy of cognitive speed of processing training (SOPT) among individuals with Parkinson disease (PD). Moderators of SOPT were also examined. Eighty-seven adults, 40 years of age or older, with a diagnosis of idiopathic PD in Hoehn & Yahr stages 1-3 and on a stable medication regimen were randomized to either 20 hours of self-administered SOPT (using InSight software) or a no-contact control condition. Participants were assessed at baseline and after 3 months of training (or an equivalent delay). The primary outcome measure was useful field of view test (UFOV) performance, and secondary outcomes included cognitive self-perceptions and depressive symptoms. Results indicated that participants randomized to SOPT experienced significantly greater improvements on UFOV performance relative to controls, Wilks λ = 0.938, F 1,72 = 4.79, p = 0.032, partial η(2) = 0.062. Findings indicated no significant effect of training on secondary outcomes, Wilks λ = 0.987, F2,70 < 1, p = 0.637, partial η(2) = 0.013. Patients with mild to moderate stage PD can self-administer SOPT and improve their cognitive speed of processing, as indexed by UFOV (a robust predictor of driving performance in aging and PD). Further research should establish if persons with PD experience longitudinal benefits of such training and if improvements translate to benefits in functional activities such as driving. This study provides Class III evidence that SOPT improves UFOV performance among persons in the mild to moderate stages of PD.

Living With Moderate-Stage Parkinson Disease

The purpose of this study was to identify the principal intervention needs of elderly couples living with moderate-stage Parkinson disease and their preferences regarding the modalities of a possible nursing intervention. The study's framework of reference consisted of the transitions theory developed by Meleis, Sawyer, Im, Hilfinger Messias, and Schumacher (2000) and of the systemic approach developed by Wright and Leahey (2009). A qualitative design and a participative process were employed. Ten couples were interviewed dyadically. Intra- and interdyad content analyses were performed. Results indicate that the principal intervention needs of couples are geared to developing effective strategies for remaining healthy and planning for the future, to improving communication between spouses and with the formal and informal support networks, and to adopting concerted strategies to facilitate problem solving and role adjustment. Couples would prefer six or seven dyadic meetings, each 60-90 minutes long, every 2 weeks, at an easily accessible location. This study affords avenues for the conceptualization of a psychoeducational nursing intervention intended for couples where a spouse has moderate-stage Parkinson disease.

Selective attention deficits in early and moderate stage Parkinson's disease

Patients with Parkinson's disease (PD) often show impaired performance on visuospatial attentional tasks. The objective of the study was to examine the attentional function of PD patients performing the attentional network test (ANT). We used the ANT to compare PD patients with healthy controls with respect to the efficiency of 3 anatomically defined attentional networks: the alerting, orienting, and executive control networks. We found that PD patients showed a selective abnormality in the orienting network. Although the alerting and executive control networks apparently remained unaffected, the efficiencies of these networks in patients with PD negatively correlated with the Hoehn–Yahr stage. The results supported the idea that the orienting processes may be more dynamic in PD than in non-PD individuals.

The effect of dopamine replacement therapy on haptic sensitivity in Parkinson’s disease

Increasing evidence indicates that processing of proprioceptive information is altered in Parkinson's disease (PD), leading to reduced kinaesthetic and haptic sensitivity. However, there is inconclusive evidence whether dopamine replacement therapy (DRT) ameliorates or worsens kinaesthetic and haptic function in PD. For assessing perceptual function, we employed a task that did not require active motion or stressed working memory function, which may become impaired in PD. A group of mild to moderate stage PD patients (n = 9) and a group of age-matched healthy controls participated in this study. Without vision, a subject's hand was moved by a robotic manipulandum along the contours of a small "virtual box" (5 × 15 cm). At the end of each trial, they indicated whether the contour was "curved" or "straight". PD patients were tested ON and OFF antiparkinsonian medication. Psychophysical detection thresholds were determined (curvature at which subjects correctly perceived a curved contour at the 75% level). Compared to the control group, thresholds were elevated by 55% in the PD patient group. During the ON medication state, the mean detection threshold of the patient group was reduced by 15% (ON: 4.71 m(-1); OFF: 5.42 m(-1)). Increases in curvature sensitivity were highly correlated with improved clinical scores of motor function (r = 0.74) with more affected patients showing higher gains in sensitivity as the result of DRT (r = 0.80). This report documents that DRT can ameliorate haptic and kinaesthetic function in patients with mild to moderate PD, suggesting that DRT can have beneficial effects on perceptual function.

Altered Resting State Cortico-Striatal Connectivity in Mild to Moderate Stage Parkinson's Disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by dopamine depletion in the striatum. One consistent pathophysiological hallmark of PD is an increase in spontaneous oscillatory activity in the basal ganglia thalamocortical networks. We evaluated these effects using resting state functional connectivity MRI in mild to moderate stage Parkinson's patients on and off l-DOPA and age-matched controls using six different striatal seed regions. We observed an overall increase in the strength of cortico-striatal functional connectivity in PD patients off l-DOPA compared to controls. This enhanced connectivity was down-regulated by l-DOPA as shown by an overall decrease in connectivity strength, particularly within motor cortical regions. We also performed a frequency content analysis of the BOLD signal time course extracted from the six striatal seed regions. PD off l-DOPA exhibited increased power in the frequency band 0.02–0.05 Hz compared to controls and to PD on l-DOPA. The l-DOPA associated decrease in the power of this frequency range modulated the l-DOPA associated decrease in connectivity strength between striatal seeds and the thalamus. In addition, the l-DOPA associated decrease in power in this frequency band correlated with the l-DOPA associated improvement in cognitive performance. Our results demonstrate that PD and l-DOPA modulate striatal resting state BOLD signal oscillations and cortico-striatal network coherence.

Pre- and post-synaptic dopamine imaging and its relation with frontostriatal cognitive function in Parkinson disease: PET studies with [ 11C]NNC 112 and [ 18F]FDOPA

Frontostriatal cognitive dysfunction is common in Parkinson disease (PD), but the explanation for its heterogeneous expressions remains unclear. This study examined the dopamine system within the frontostriatal circuitry with positron emission tomography (PET) to investigate pre- and post-synaptic dopamine function in relation to the executive processes in PD. Fifteen non-demented PD patients and 14 healthy controls underwent [ 18F]FDOPA (for dopamine synthesis) and [ 11C]NNC 112 (for D 1 receptors) PET scans and cognitive testing. Parametric images of [ 18F]FDOPA uptake ( K i) and [ 11C]NNC 112 binding potential (BP ND) were calculated using reference tissue models. Group differences in K i and BP ND were assessed with both volume of interest and statistical parametric mapping, and were correlated with cognitive tests. Measurement of [ 18F]FDOPA uptake in cerebral cortex was questionable because of higher K i values in white than adjacent gray matter. These paradoxical results were likely to be caused by violations of the reference tissue model assumption rendering interpretation of cortical [ 18F]FDOPA uptake in PD difficult. We found no regional differences in D 1 receptor density between controls and PD, and no overall differences in frontostriatal performance. Although D 1 receptor density did not relate to frontostriatal cognition, K i decreases in the putamen predicted performance on the Wisconsin Card Sorting Test in PD only. These results suggest that striatal dopamine denervation may contribute to some frontostriatal cognitive impairment in moderate stage PD.