The influence of dopaminergic medication on balance automaticity in Parkinson’s disease

BackgroundStudies have shown that dual-task standing balance in Parkinson’s disease (PD) is significantly diminished. Additionally, it is well accepted that dopaminergic medication improves dynamic balance (Berg Balance Scale, mini-BESTest), but standing balance (force platform posturography) may suffer. What remains unknown is how dopaminergic medication influences standing balance automaticity in PD.Research questionDoes dopaminergic medication improve standing balance automaticity during a phoneme monitoring dual-task in PD?MethodsThis was a cross-sectional study. Sixteen subjects with PD completed single- and dual-task standing with eyes open and eyes closed for 3 min each in off and on medication states. 95% confidence ellipse area, anterior-posterior sway velocity, medial-lateral sway velocity, and integrated time to boundary were calculated. Data were analyzed with a repeated measures ANOVA.ResultsDopaminergic medication significantly increased ellipse area (p = 0.002) and decreased the performance on the secondary task (p = 0.004). Different eyes conditions (open vs. closed) significantly increased both sway velocities (anterior-posterior = p < 0.001, medial-lateral = p < 0.001), and increased integrated time to boundary (p < 0.001). There were also task by eyes condition interaction effects for anterior-posterior velocity and integrated time to boundary (p = 0.015 and p = 0.009, respectively). Increases in sway velocity and integrated time to boundary seen in the eyes condition and interaction effects are traditionally interpreted as poorer balance performance. However, in the context of stability/maneuverability tradeoff, the changes may indicate an increase in freedom of movement instead of a decrease in stability.SignificanceThe data did not support a medication-induced improvement in automaticity, as measured by significant medication by task interactions. An alternate interpretation for medication-induced balance changes in PD includes an increase in maneuverability without sacrificing stability after taking dopaminergic medication.     

Underwater gait analysis in Parkinson’s disease

Although hydrotherapy is one of the physical therapies adopted to optimize gait rehabilitation in people with Parkinson disease, the quantitative measurement of gait-related outcomes has not been provided yet. This work aims to document the gait improvements in a group of parkinsonians after a hydrotherapy program through 2D and 3D underwater and on land gait analysis. Thirty-four parkinsonians and twenty-two controls were enrolled, divided into two different cohorts. In the first one, 2 groups of patients underwent underwater or land based walking training; controls underwent underwater walking training. Hence pre-treatment 2D underwater and on land gait analysis were performed, together with post-treatment on land gait analysis. Considering that current literature documented a reduced movement amplitude in parkinsonians across all lower limb joints in all movement planes, 3D underwater and on land gait analysis were performed on a second cohort of subjects (10 parkinsonians and 10 controls) who underwent underwater gait training. Baseline land 2D and 3D gait analysis in parkinsonians showed shorter stride length and slower speed than controls, in agreement with previous findings. Comparison between underwater and on land gait analysis showed reduction in stride length, cadence and speed on both parkinsonians and controls. Although patients who underwent underwater treatment exhibited significant changes on spatiotemporal parameters and sagittal plane lower limb kinematics, 3D gait analysis documented a significant (p < 0.05) improvement in all movement planes. These data deserve attention for research directions promoting the optimal recovery and maintenance of walking ability.     

Resting state functional networks predict different aspects of postural control in Parkinson’s disease

BackgroundParkinson’s disease (PD) is a neurodegenerative disorder causing postural control impairments. Postural control involves multiple domains, such as control of postural sway in stance, automatic postural responses (APRs) and anticipatory postural adjustments (APAs). We hypothesize that impairments in each postural domain is associated with resting-state functional connectivity (rsFC), accounted by predictive modeling and that cortical and cerebellar networks would predict postural control in people with PD (PwPD).ObjectiveTo determine whether rsFC can predict three domains of postural control independently in PwPD and older adults (OA) based on predictive accuracy of models.MethodsThe cohort consisted of 65 PwPD (67.7 +8.1 age) tested in their OFF-state and 42 OA (69.7 +8.2 age). Six body-worn, inertial sensors measured postural sway area while standing on foam, step length of APRs to a backward push-and-release perturbation, and magnitude of lateral APAs prior to voluntary gait initiation. Resting state-fMRI data was reported on 384 regions of interest that were grouped into 13 functional brain networks. Associations between rsFC and postural metrics were characterized using predictive modeling, with an independent training (n = 67) and validation (n = 40) dataset. Models were trained in the training sample and performance of the best model was validated in the independent test dataset.ResultsrsFC of different brain networks predicted each domain of postural control in PD: Frontoparietal and Ventral Attention rsFC for APAs; Cerebellar-Subcortical and Visual rsFC and Auditory and Cerebellar-Subcortical rsFC for APRs; Ventral Attention and Ventral Multimodal rsFC for postural sway. In OA, CinguloOpercular and Somatomotor rsFC predicted APAs.ConclusionsOur findings suggest that cortical networks predict postural control in PD and there is little overlap in brain network connectivities that predict different domains of postural control, given the rsFC methodology used. PwPD use different cortical networks for APAs compared to OA.     

Substantia innominata: MR findings in Parkinson’s disease

To elucidate MR imaging changes of the substantia innominata in Parkinsons disease (PD), using a 1.5-T superconductive MR unit, the thickness of the substantia innominata was measured on coronal thin-section images in 44 PD patients and 20 age-matched control subjects. We also evaluated the correlation between the thickness of the substantia innominata and mental status in PD patients. Mean thickness of the substantia innominata was 2.3 mm in PD patients, and 2.5 mm in control subjects. Thinning of the substantia innominata was statistically significant in PD patients compared with control subjects, although there were large overlaps. Among the PD patients, thinning was remarkable in cases with dementia. A positive correlation between thickness of substantia innominata and score of Mini-Mental-Status-Examination was also observed in PD patients. Atrophy of the substantia innominata was demonstrated, especially in PD patients with cognitive impairment, on coronal MR images, and this is compatible with the previous pathological reports.     

Distinct spatiotemporal patterns for disease duration and stage in Parkinson’s disease

Purpose

To assess correlations between the degree of dopaminergic depletion measured using single-photon emission computed tomography (SPECT) and different clinical parameters of disease progression in Parkinson’s disease (PD).

Methods

This retrospective study included 970 consecutive patients undergoing ¹²³I-ioflupane SPECT scans in our institution between 2003 and 2013, from which we selected a study population of 411 patients according to their clinical diagnosis: 301 patients with PD (69.4?±?11.0 years, of age, 163 men) and 110 patients with nondegenerative conditions included as controls (72.7?±?8.0 years of age, 55 men). Comprehensive and operator-independent data analysis included spatial normalization into standard space, estimation of the mean uptake values in the striatum (caudate nucleus + putamen) and voxel-wise correlation between SPECT signal intensity and disease stage as well as disease duration in order to investigate the spatiotemporal pattern of the dopaminergic nigrostriatal degeneration. To compensate for potential interactions between disease stage and disease duration, one parameter was used as nonexplanatory coregressor for the other.

Results

Increasing disease stage was associated with an exponential decrease in ¹²³I-ioflupane uptake (R ² ?=?0.1501) particularly in the head of the ipsilateral caudate nucleus (p?<?0.0001), whereas increasing disease duration was associated with a linear decrease in ¹²³I-ioflupane uptake (p?<?0.0001; R ² ?=?0.1532) particularly in the contralateral anterior putamen (p?<?0.0001).

Conclusion

We observed two distinct spatiotemporal patterns of posterior to anterior dopaminergic depletion associated with disease stage and disease duration in patients with PD. The developed operator-independent reference database of 411 ¹²³I-ioflupane SPECT scans can be used for clinical and research applications.

     

Non-motor predictors of freezing of gait in Parkinson’s disease

BackgroundThe etiology of freezing of gait in Parkinson’s disease (PD) is yet to be clarified. Non-motor risk factors including cognitive impairment, sleep disturbance and mood disorders have been shown in freezing of gait.Research questionWe aimed to determine the predictive value of non-motor features in freezing of gait development.MethodsData were obtained from the Parkinson’s Progression Markers Initiative. Fifty PD patients with self-reported freezing of gait, and 50 PD patients without freezing of gait at the fourth year visit were included. Groups were matched for Movement Disorders Society-Unified Parkinson’s Disease Rating Scale Part III scores. Several cognitive and non-cognitive tests were used for non-motor features at baseline and over time. Executive function, visuospatial function, processing speed, learning and memory tests were used for cognition. Non-cognitive tests included sleepiness, REM sleep behavior disorder, depression and anxiety scales.ResultsPatients with freezing of gait had higher scores on sleepiness, REM sleep behavior disorder, depression and anxiety scales. However, predictor model analysis revealed that baseline processing speed, learning and sleepiness scores were predictive of self-reported freezing of gait development over time.SignificanceOur findings suggest that specific cognitive deficits and sleep disorders are predictive of future freezing of gait. These features may be helpful in identifying underlying networks in freezing of gait and should be further investigated with neuroimaging studies.     

Brain perfusion alterations in depressed patients with Parkinson’s disease

Objective

Although Parkinson’s disease (PD) is frequently accompanied by depression, brain perfusion deficits in PD with depression remain unclear. This study aimed to assess alterations in regional cerebral blood flow (rCBF) in depressed PD patients using ^99mTc hexamethyl-propylene-amine-oxime single-photon emission computed tomography (SPECT).

Methods

Among 78 patients with PD, 35 patients were classified into the depressed PD group, while the rest (43 patients) was assigned to the nondepressed PD group based on the scores of the Geriatric Depressive Scale (GDS). All participants underwent brain SPECT imaging. The voxel-wise whole-brain analysis and region-of-interest (ROI) analysis of the limbic areas were conducted to compare rCBF between the depressed and nondepressed PD groups.

Results

The depressed PD patients demonstrated higher GDS scores than nondepressed patients, whereas between-group differences in the PD severity and cognitive function were not significant. Perfusion in the left cuneus was increased, while that in the right superior temporal gyrus and right medial orbitofrontal cortex was reduced in the depressed PD patients as compared with nondepressed PD patients. In addition, the ROI analysis demonstrated rCBF decreases in the amygdala, anterior cingulate cortex, hippocampus, and parahippocampal gyrus in the depressed PD group. A positive correlation was found between the GDS scores and rCBF in the left cuneus cluster in the depressed PD patients.

Conclusion

This study identified the regional pattern of brain perfusion that distinguished depressed from nondepressed PD patients. Hyperperfusion in the occipital areas and hypoperfusion in the fronto-temporo-limbic regions may be potential imaging biomarkers for depression in PD.

     

Treadmill walking alters stride time dynamics in Parkinson’s disease

BackgroundTreadmill training may be used to improve gait rhythmicity in people with Parkinson’s disease. Treadmills, however, alter dynamical stride time fluctuations in healthy adults in a manner that mimics pathologic states, indicating the stride-to-stride fluctuations that characterize healthy gait are constrained. It is unclear if treadmills similarly alter dynamic gait properties in Parkinson’s disease.Research questionDo stride time fractal dynamics in individuals with Parkinson’s disease differ between treadmill and overground walking?MethodsFifteen participants with Parkinson’s disease and 15 healthy age-similar adults walked for 6 min in a conventional overground condition and on a treadmill while wearing inertial measurement units. Gait speed, stride times and stride time variability were measured. Fractal exponents (α) were computed with adaptive fractal analysis. Inferential statistics were analyzed with mixed model analyses of variance and post hoc simple effects tests.ResultsMean gait speeds decreased and stride times increased on the treadmill but did not differ between the Parkinson’s and control groups. Stride time variability was greater in the Parkinson’s than control group in both conditions. Most relevant to our research question, stride time fractal exponents were greater on the treadmill (mean α = .910) than overground (mean α = .797) in individuals with Parkinson’s disease, but not in healthy controls.SignificanceThe fractal scaling exponent α emanating from stride time fluctuations during treadmill walking increased toward a 1/f signal of α = 1.0 that has been interpreted as an optimal structural variability for gait. The clinical implication is that treadmill training may promote more efficient walking dynamics in people with Parkinson’s disease than conventional overground training.     

Effect of subthalamic nucleus deep brain stimulation on balance in Parkinson’s disease: A static posturographic analysis

BackgroundThe effect of subthalamic deep brain stimulation on balance in Parkinson’s disease remains unclear.ObjectiveTo evaluate the effect of subthalamic nucleus stimulation on balance in Parkinson’s disease using posturography.Methods16 patients (9 women) who underwent subthalamic deep brain stimulation [mean age 59.6 years (46–70); mean disease duration 15.6 years (7–25); mean duration of subthalamic stimulation 32.1 months (3.0–69.6)] and 13 healthy age-matched controls were evaluated using a static posturography analysis. Patients were assessed under four conditions: 1) off medication/off stimulation; 2) off medication/on stimulation; 3) on medication/off stimulation and 4) on medication/on stimulation in ten experimental paradigms, some reproducing common situations of daily living. The displacement of the centre of pressure was analyzed using 14 posturographic parameters. The Mann-Whitney test was used to compare patients with controls. The Wilcoxon signed rank test was used to compare patients under different clinical conditions.ResultsPatients off medication/off stimulation showed larger and more rapid displacements of the centre of pressure than controls in most paradigms (p < 0.05), particularly when performing a dual task. Subthalamic stimulation alone reduced the lateral excursion and anterior-posterior velocity of the centre of pressure in quite stance paradigms (p < 0.05). Subthalamic stimulation combined with antiparkinsonian medication did not induce statistically significant changes in posturagraphic measures in any experimental paradigm.ConclusionsAlthough subthalamic stimulation alone may induce some positive effect on balance, subthalamic stimulation in addition to antiparkinsonian medication, which is the usual treatment in clinical practice, did not modify balance as assessed by static posturography in patients with Parkinson’s disease.     

Biomechanical measures of balance after balance-based exergaming training dedicated for patients with Parkinson’s disease

IntroductionAlthough previous studies have contributed to our understanding of the effects of implementing the virtual reality as a rehabilitation tool in patients with Parkinson’s disease (PD), additional research is needed to examine the effects of applying balance-based exergaming training on quantitative biomechanical measures of balance.Research questionTo investigate the effects of balance-based conventional and exergaming training on posture parameters.MethodsThe study involved 24 patients with PD (Hoehn and Yahr stages II-III).Participants underwent twelve training sessions during the 4-week training period. The experimental group (n=12) was trained with a custom-made exergaming balance based training system, the control group (n=12) underwent a conventional balance training.All objective outcomes were measured before intervention and the day after completion of training program. Postural stability was assessed using the quiet standing test, dynamic balance was assessed using limits of stability (LOS) and functional balance (FBT) tests.ResultsAfter training, participants in both groups showed significantly better results in static balance performance. However, only exergaming training significantly improved LOS performance (higher values of Range of forward lean (p = 0.039, d_z = 0.67) and leaning rate (p=0.007, d_z=0.96). Also FBT test improved significantly only in experimental group (decrease in time to target hit (p=0.02, d_z=0.76) and significant increase of average COP velocity (p=0.008, d_z=0.93).ConclusionThis study found that exergaming training created for patients with PD enhanced static and dynamic balance whereas conventional balance training improved static balance. Posturography is sensitive enough to reveal differential effects of training for both groups. These findings support the inclusion of our exergaming training in the exercise program for participants with PD.     

Immediate effects of perturbation treadmill training on gait and postural control in patients with Parkinson’s disease

The study investigates immediate adaptations of gait and balance to a single session of perturbed treadmill walking in patients with Parkinson’s disease. 39 Parkinson’s patients in stage 1–3.5 of the Hoehn and Yahr Scale were randomized into one of two groups, stratified by disease severity: The experimental group (n = 19) walked on a treadmill prototype which constantly applied perturbation by small three-dimensional tilting movements of the walking surface. The control group (n = 20) trained on the identical treadmill without perturbations. Patients walked on the treadmill for 20 min. Primary outcome measure was overground walking speed. Secondary outcomes were postural sway during quiet standing and spatiotemporal gait parameters during treadmill walking. Outcomes were measured repeatedly throughout the training session and after 10 min retention. The experimental group significantly increased overground walking speed after intervention compared to the control group (p = 0.014; ES = +0.41). Gait variability during treadmill walking significantly decreased after walking with perturbation. Sway area increased with treadmill walking only in the control group (p = 0.009; ES = +0.49). No other postural sway measures changed over time. Subgroup analyses revealed that in the experimental group patients with more pronounced motor impairment demonstrated larger increases in overground walking speed (p = 0.016; ES = +0.40) and stance phase symmetry (p = 0.011; ES = −0.42). In conclusion, a single session of perturbation treadmill training led to gait improvements, which were more pronounced compared to unperturbed treadmill walking. Effects on static postural sway were less pronounced.     

Recent advances in PET imaging for evaluation of Parkinson’s disease

Parkinson’s disease (PD) consists of loss of pigmented dopamine-secreting neurons in the pars compacta of the midbrain substantia nigra. These neurons project to the striatum (putamen and caudate nucleus) and their loss leads to alterations in the activity of the neural circuits that regulate movement. In a simplified model, two dopamine pathways are involved: the direct pathway, which is mediated through facilitation of the D₁ receptors, and the indirect pathway through D₂ receptors (inhibitory). Positron emission tomography (PET) tracers to image the presynaptic sites of the dopaminergic system include 6-[¹⁸F]FDOPA and 6-[¹⁸F]FMT, [¹¹C]dihydrotetrabenazine, [¹¹C]nomifensine and various radiolabelled cocaine derivatives. Postsynaptically, for the dopamine D₁ subtype the most commonly used ligands are [¹¹C]SCH 23390 or [¹¹C]NNC 112 and for the D₂ subtype [¹¹C]raclopride, [¹¹C]MNPA and [¹⁸F]DMFP. PET is a sensitive and specific non-invasive molecular imaging technique that may be helpful for evaluation of PD and its differential diagnosis from other parkinsonian syndromes.     

Cortical activation during gait adaptability in people with Parkinson’s disease

BackgroundPeople with Parkinson’s disease (PD) have difficulties adapting their gait. While underlying neural mechanisms involving the prefrontal cortex (PFC) have been studied across various complex walking tasks, less is known about the premotor cortex (PMC) and supplementary motor area (SMA), key cortical regions for motor planning. This study compared frontal cortical regions activation patterns using functional near-infrared spectroscopy (fNIRS), between people with PD and healthy controls (HC) during gait adaptability tasks.MethodsForty-nine people with PD (mean (SD) age: 69.5 (7.9) years) and 21 HC (69.0 (5.9) years) completed a simple walk and three randomly presented gait adaptability tasks: (i) stepping on targets, (ii) avoiding obstacles and (iii) negotiating both targets and obstacles. Cortical activity in the dorsolateral PFC (DLPFC), SMA and PMC were recorded using fNIRS. Step length, velocity and accuracy and cortical activity were contrasted between the groups and walking conditions.ResultsCompared with the HC, the PD group exhibited greater PMC activation and walked significantly slower and took shorter steps in all conditions. A statistically significant group by condition interaction indicated an increase in DLPFC cortical activation in the HC participants when undertaking the obstacle avoidance task compared with the simple walk but no increase in cortical activation in the PD group when undergoing this more challenging gait task.ConclusionsOur findings suggest people with PD have little or no DLPFC, SMA and PMC capacity beyond what they need for simple walking and in consequence need to slow their gait velocity to meet the demands of target stepping and obstacle avoidance tasks. Such behavioral and neural patterns appear consistent with concepts of compensatory over-activation and capacity limitation.     

Use of ACE-inhibitors and falls in patients with Parkinson’s disease

Falls represent a major concern in patients with Parkinson’s disease (PD); however, currently acknowledged treatments for PD are not effective in reducing the risk of falling. The aim was to assess the association of use of ACE-inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) with falls among patients with PD.We analysed data of 194 elderly with PD attending a geriatric Day Hospital. Self-reported history of falls that occurred over the last year, as well as use of drugs, including ACEIs and angiotensin II receptor blockers (ARBs) were recorded. The association of the occurrence of any falls with use of ACEIs, and ARBs was assessed by logistic regression analysis. The association between the number of falls and use of ACEIs, and ARBs was assessed according to Poisson regression.In logistic regression, after adjusting for potential confounders, use of ACEIs was associated with a reduced probability of falling over the last year (OR = 0.15, 95% CI = 0.03–0.81; P = 0.028). This association did not vary with blood pressure levels (P for the interaction term = 0.528). Also, using Poisson regression, use of ACEIs predicted a reduced number of falls among participants who fell (PR = 0.31; 95% CI = 0.10–0.94; P = 0.039). No association was found between use of ARBs and falls.Our results indicate that use of ACEIs might be independently associated with reduced probability, and a reduced number of falls among patients with PD. Dedicated studies are needed to define the single agents and dosages that might most effectively reduce the risk of falling in clinical practice.     

Test-retest reliability of stride length-cadence gait relationship in Parkinson’s disease

IntroductionThe gait pattern in Parkinson´s disease (PD) subjects is characterized by a specific deficit of the internal regulation of the stride length (SL), while the control of the cadence (Cad) remains intact. The purpose of the present study was to evaluate the reliability of the stride length-cadence relationship (SLCrel) in a group of PD subjects.MethodsThirty five PD subjects performed two sessions, separated by a three month resting period. In each session Gait speed, SL and Cad were evaluated at five different self-selected speed conditions: preferred, slow, very slow, fast and very fast. Linear regression analysis was used to explore the SLCrel and to determine the slope, intercept and coefficient of determination (R²) for each participant. Test-retest reliability for the slope and intercept was calculated using intra-class correlation coefficient (ICC), 95% confidence interval (CI), and standard error of mean (SEM).ResultsThere were no significant differences in the slope and intercept between the two sessions. The overall speed was significantly faster in the second session compared with the first one (F = 4.60, p = 0.03). The SLCrel showed high reliability across the sessions (ICC = 0.89 and ICC = 0.91; 95% CI = 0.80−0.95 and 95% CI = 0.82−0.95; SEM = 0.002 and SEM = 0.073, for the slope and interception, respectively).ConclusionsThe SLCrel in Parkinsonian gait is a reproducible measure across a period of three months, and may be a useful tool to explore the specificity of gait rehabilitation interventions in PD subjects.     

Differences in predictors for gait speed and gait endurance in Parkinson’s disease

IntroductionBoth gait speed and gait endurance directly impact independence and community engagement for individuals with Parkinson’s disease (PD). However, factors accounting for variability in gait speed and gait endurance performance are unclear. The purpose of this study was to investigate whether key factors associated with gait speed in individuals with PD also predicted gait endurance.MethodsCommunity dwelling ambulatory individuals with PD were recruited for a single session. Key measures included 10 Meter Walk Test (10MWT) and 6 Minute Walk Test (6MWT) and key factors: age, disease severity [Movement Disorders Society United Parkinson’s Disease Rating Scale (motor scale only) (MDS-UPDRS motor)], plantar flexor strength [Calf Raise Senior (CRS)], fatigue [Fatigue Severity Scale (FSS)], cognition [Montreal Cognitive Assessment (MoCA)], and balance [Four Square Step Test (FSST)]. Multiple linear regression analyses were conducted to determine clinical relationships.ResultsSeventy-two individuals with PD (mean (standard deviation) (age = 70.83 (7.91) years; 50 males; MDS-UPDRS motor = 30.67 (13.50)) completed all assessments. The model predicting gait speed was significant, F(6, 65) = 15.143, p <.001, accounting for 54 % of the variance. Of the predictor variables age, MDS-UPDRS motor, CRS, MoCA and FSST scores were significant predictors. The model predicting gait endurance was significant, F(6, 65) = 15.608, p <.001, accounting for 55 % of the variance. Of the predictor variables, age, MDS-UPDRS motor scale, and CRS scores were significant predictors.DiscussionGait speed and gait endurance are similarly influenced by age, motor impairment, and plantarflexion strength. However, cognition and balance were predictors only of gait speed, which may suggest unique task differences exist between gait speed and gait endurance.