Phenotype of postural instability/gait difficulty in Parkinson disease: relevance to cognitive impairment and mechanism relating pathological proteins and neurotransmitters.
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ABSTRACT:
SUBMITTER: Zuo LJ
PROVIDER: S-EPMC5362957 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Characterizing motor subtypes of Parkinson's disease (PD) is an important aspect of clinical care that is useful for prognosis and medical management. Although all PD cases involve the loss of dopaminergic neurons in the brain, individual cases may present with different combinations of motor signs, which may indicate differences in underlying pathology and potential response to treatment. However, the conventional method for distinguishing PD motor subtypes involves resource-intensive physical examination by a movement disorders specialist. Moreover, the standardized rating scales for PD rely on subjective observation, which requires specialized training and unavoidable inter-rater variability. In this work, we propose a system that uses machine learning models to automatically and objectively identify some PD motor subtypes, specifically Tremor-Dominant (TD) and Postural Instability and Gait Difficulty (PIGD), from 3D kinematic data recorded during walking tasks for patients with PD (MDS-UPDRS-III Score, 34.7 ± 10.5, average disease duration 7.5 ± 4.5 years). This study demonstrates a machine learning model utilizing kinematic data that identifies PD motor subtypes with a 79.6% F1 score (N = 55 patients with parkinsonism). This significantly outperformed a comparison model using classification based on gait features (19.8% F1 score). Variants of our model trained to individual patients achieved a 95.4% F1 score. This analysis revealed that both temporal, spectral, and statistical features from lower body movements are helpful in distinguishing motor subtypes. Automatically assessing PD motor subtypes simply from walking may reduce the time and resources required from specialists, thereby improving patient care for PD treatments. Furthermore, this system can provide objective assessments to track the changes in PD motor subtypes over time to implement and modify appropriate treatment plans for individual patients as needed.
| S-EPMC10575216 | biostudies-literature
Project description:Background:Weight loss in Parkinson's disease (PD) patients is a common but poorly understood manifestation. Several studies have reported that weight changes could be related to motor symptoms, drug side effects, dysphagia, depression, and/or dementia. Weight loss in PD is not a benign phenomenon and it has several clinical and prognostic implications with increased morbidity and mortality. Thus, it is crucial to determine nutritional changes in PD patients in order to prevent malnutrition and improve their quality of life. Objective:To compare body composition and resting metabolic rates between PD patients and controls. Methods:A total of 64 PD patients and 52 controls were studied. The Hoehn-Yahr scale was used to determine the disease stage, clinical and epidemiological data were recorded from verbal questionnaire, Inbody S10® was used to collect corporal parameters, and FitMate system was used to assess the resting metabolic rate. Results:No significant differences were found between both experimental groups in age, gender, height, cholesterol levels, and the presence of hypertension, diabetes, and hypo/hyperthyroidism. However, the PD group showed lower body fat mass, whole-body fat percentage, and greater resting metabolic rate compared to controls (p < 0.05), with no significant differences in musculoskeletal mass. Parkinson's disease postural instability/gait difficulty (PD-PIGD) subtype showed lower body fat parameters, increased fat-free mass, and higher resting metabolic rates. Conclusions:These results suggest that PD patients present an increased resting metabolic rate associated with the postural instability/gait difficulty PD subtype, allowing a selective decrease of body fat mass and not musculoskeletal mass. Of note, several disease-related factors may contribute to this weight loss in PD patients, being a complex and multifactorial consequence. Our findings could likely be one of the many contributing factors. However, present findings may further add to our understanding of the phenomenon of weight loss in patients with PD.
| S-EPMC7103052 | biostudies-literature
Project description:ObjectiveTo determine whether varenicline is effective for the balance in Parkinson disease (PD).MethodsThis was an investigator-initiated, double-blind, placebo-controlled study. Participants with a clinical diagnosis of PD were randomized to receive varenicline or placebo for 8 weeks. After dose escalation, participants took 1 mg of drug twice daily until the end of the study. Patients with severe tremor were excluded. Primary outcome was a change on the Berg Balance Scale (BBS) from baseline to 8 weeks. The BBS is a 14-item measure consisting of basic balance tasks. The study had a secondary, exploratory outcome of a change in cognition, measured with the Frontal Assessment Battery (FAB) and the Mini-Mental State Exam (MMSE) from baseline to 8 weeks. The FAB is a 6-item measure of executive functioning.ResultsThirty-six participants were randomized (82% men, 100% White). Average age was 71.0 years (± 8.1). Average baseline motor Movement Disorder Society Unified Parkinson's Disease Rating Scale was 34.7 (± 11.6). There were no differences between treatment groups on the BBS (F[1,28] = 2.85, p = 0.10) or FAB (d = 0.16, 95% confidence interval [CI] = [-1.39 to 1.53]) or MMSE (d = 0.81, 95% CI = [-0.40 to 1.40]).ConclusionThe results did not suggest that varenicline had an effect on balance in patients with PD. Furthermore, varenicline did not seem to affect cognition. Perhaps, if an objective measure of balance had been used in place of the BBS, the analysis would show a difference between the groups. However, the authors do not recommend further study.Classification of evidenceThis study provides Class III evidence that in patients with PD with Hoehn and Yahr stages 2, 3, or 4, varenicline does not improve balance as assessed by the BBS.
| S-EPMC8723959 | biostudies-literature
Project description:Background and purposeIn people with Parkinson disease (PD), difficulties with initiating stepping may be related to impairments of anticipatory postural adjustments (APAs). Increased variability in step length and step time has been observed in gait initiation in individuals with PD. In this study, we investigated whether the ability to generate consistent APAs during gait initiation is compromised in these individuals.MethodsFifteen subjects with PD and 8 healthy control subjects were instructed to take rapid forward steps after a verbal cue. The changes in vertical force and ankle marker position were recorded via force platforms and a 3-dimensional motion capture system, respectively. Means, standard deviations, and coefficients of variation of both timing and magnitude of vertical force, as well as stepping variables, were calculated.ResultsDuring the postural phase of gait initiation the interval was longer and the force modulation was smaller in subjects with PD. Both the variability of timing and force modulation were larger in subjects with PD. Individuals with PD also had a longer time to complete the first step, but no significant differences were found for the variability of step time, length, and speed between groups.Discussion and conclusionsThe increased variability of APAs during gait initiation in subjects with PD could affect posture-locomotion coupling, and lead to start hesitation, and even falls. Future studies are needed to investigate the effect of rehabilitation interventions on the variability of APAs during gait initiation in individuals with PD.Video abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A119).
| S-EPMC5568770 | biostudies-literature
Project description:Gait disorders and postural instability, which are commonly observed in elderly patients with Parkinson disease (PD), respond poorly to dopaminergic agents used to treat other parkinsonian symptoms. The brain structures underlying gait disorders and falls in PD and aging remain to be characterized. Using functional MRI in healthy human subjects, we have shown here that activity of the mesencephalic locomotor region (MLR), which is composed of the pedunculopontine nucleus (PPN) and the adjacent cuneiform nucleus, was modulated by the speed of imagined gait, with faster imagined gait activating a discrete cluster within the MLR. Furthermore, the presence of gait disorders in patients with PD and in aged monkeys rendered parkinsonian by MPTP intoxication correlated with loss of PPN cholinergic neurons. Bilateral lesioning of the cholinergic part of the PPN induced gait and postural deficits in nondopaminergic lesioned monkeys. Our data therefore reveal that the cholinergic neurons of the PPN play a central role in controlling gait and posture and represent a possible target for pharmacological treatment of gait disorders in PD.
| S-EPMC2912198 | biostudies-literature
Project description:To test the hypothesis that postural instability with falling (PIF) and freezing of gait (FOG) are distinct subtypes of the postural instability/gait disturbance (PIGD) form of Parkinson's disease (PD).499 PD subjects from the NeuroGenetics Research Consortium were studied using logistic regression to examine, in a cross sectional analysis, predictors of FOG and PIF. Potential predictors were from four spheres; demographic, clinical motor, clinical non-motor and genetic.FOG and PIF were both associated with greater gait subscores and lower tremor subscores on the Unified Parkinson's Disease Rating Scale (p ? 0.02). However, they differed with regard to demographic, non-motor and genetic predictors. FOG was associated with greater duration of disease, with ORs of 3.01 (95% CI 1.35 to 6.72) and 4.91 (95% CI 2.29 to 10.54) for third and fourth quartiles of duration, respectively, versus the lowest half of duration. The risk of having psychotic symptoms was also significantly increased (OR 3.02, 95% CI 1.41 to 6.49; p=0.004). FOG was inversely associated with the presence of the CYP2D6*4 allele (OR 0.41, 95% CI 0.21 to 0.80; p=0.009) suggesting a protective effect. PIF was associated with depression (OR 1.08, 95% CI 1.01 to 1.15; p<0.02) and was inversely associated with APOE ?4 (OR 0.21, 95% CI 0.05 to 0.87; p=0.03), again suggesting a protective effect.FOG and PIF have different demographic, non-motor and genetic predictors suggesting that they may be pathophysiologically distinct subtypes of PIGD. These findings have implications in the discovery of therapeutic targets for these disabling features as well as for predicting outcomes of PD.
| S-EPMC4646086 | biostudies-literature
Project description:BackgroundThere is a paucity of therapies for gait impairment in Parkinson disease (PD). Open-label studies have suggested improved gait after treatment with methylphenidate (MPD).ObjectiveTo evaluate the efficacy of MPD for the treatment of gait impairment in PD.MethodsTwenty-seven subjects with PD and moderate gait impairment were screened for this 6-month placebo-controlled, double-blind study. Subjects were randomly assigned to MPD (maximum, up to 80 mg/day) or placebo for 12 weeks and crossed over after a 3-week washout. The primary outcome measure was change in a gait composite score (stride length + velocity) between groups at 4 and 12 weeks. Secondary outcome measures included changes in motor function, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS), Freezing of Gait Questionnaire (FOGQ), number of gait-diary freezing episodes, and measures of depression, sleepiness, and quality of life. Three-factor repeated-measures analysis of variance was used to measure changes between groups.ResultsTwenty-three eligible subjects with PD were randomized and 17 completed the trial. There was no change in the gait composite score or treatment or time effect for any of the variables. Treatment effect was not modified by state or study visit. Although there was a trend for reduced frequency of freezing and shuffling per diary, the FOGQ and UPDRS scores worsened in the MPD group compared to placebo. There was a marginal improvement in some measures of depression.ConclusionsMPD did not improve gait and tended to worsen measures of motor function, sleepiness, and quality of life.Classification of evidenceThis study provides Class III evidence for the lack of benefit of MPD on PD-associated gait impairment.Clinical trial registrationNCT00526630.
| S-EPMC3068005 | biostudies-literature
Project description:BackgroundParkinson's Disease patients with predominant gait dysfunction appear to have reduced cortical thickness compared to other motor phenotypes. The extent to which advancing age or disease duration impact the pattern of these distinctions is unclear.ObjectiveWe examine if PD patients with predominant signs of postural instability and gait dysfunction are distinguished by distinct patterns of cerebral atrophy, and how these differences are influenced by age and disease duration.MethodsThe Unified Parkinson's Disease Rating Score (UPDRS) was administered to 196 PD patients (age = 61.4±8.9yrs) in the Off and On dopamine state. All completed a structural T1-weighted brain MRI. We defined 3 motor phenotypes: tremor dominant, akinetic-rigid, and postural instability with gait disorder. General linear modeling quantified cortical thickness in relation to disease duration, and motor improvement after dopaminergic therapy. Cortical thickness and subcortical volumes were compared between the three motor subtypes, after controlling for disease duration and age.ResultsWe identified 177/196 patients who met criteria for a motor subtype. When corrected for disease duration, postural-instability patients had marked cortical thinning of the bilateral frontal-temporal and posterior cortical regions (cuneus/precuneus). After regressing for age, reduced frontal thickness was evident in patients with gait dysfunction. Widespread cortical thinning was associated with increasing disease duration and reduced motor improvement to dopaminergic therapy.ConclusionsResults emphasize that the profile of motor signs, especially prominent gait manifestations, relate to cortical thinning in distinct regions. Unique patterns of atrophy appear to be driven by advancing pathology related to age and disease duration.
| S-EPMC5826542 | biostudies-literature
Project description:Postural instability/gait disturbance (PIGD) is very common in advanced Parkinson's disease, and associated with cognitive dysfunction. Research suggests that low frequency (5-12 Hz) subthalamic nucleus-deep brain stimulation (STN-DBS) could improve cognition in patients with Parkinson's disease (PD). However, the clinical effectiveness of low frequency stimulation in PIGD patients has not been explored. This study was designed in a double-blinded randomized cross-over manner, aimed to verify the effect of low frequency STN-DBS on cognition of PIGD patients. Twenty-nine PIGD patients with STN-DBS were tested for cognitive at off (no stimulation), low frequency (5 Hz), and high frequency (130 Hz) stimulation. Neuropsychological tests included the Stroop Color-Word Test (SCWT), Verbal fluency test, Symbol Digital Switch Test, Digital Span Test, and Benton Judgment of Line Orientation test. For conflict resolution of executive function, low frequency stimulation significantly decreased the completion time of SCWT-C (p = 0.001) and Stroop interference effect (p < 0.001) compared to high frequency stimulation. However, no significant differences among stimulation states were found for other cognitive tests. Here we show, low frequency STN-DBS improved conflict resolution of executive function compared to high frequency. Our results demonstrated the possibility of expanding the treatment coverage of DBS to cognitive function in PIGD, which will facilitate integration of low frequency stimulation into future DBS programming.
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Project description:Primary progressive aphasias (PPAs) are a group of neurodegenerative diseases mainly characterized by language impairment, and with variably presence of dysexecutive syndrome, behavioural disturbances and parkinsonism. Detailed knowledge of neurotransmitters impairment and its association with clinical features hold the potential to develop new tailored therapeutic approaches. In the present study, we applied JuSpace toolbox, which allowed for cross-modal correlation of magnetic resonance imaging (MRI)-based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, GABAergic and glutamatergic neurotransmission. We included 103 PPA patients and 80 age-matched healthy controls (HC). We tested if the spatial patterns of grey matter volume (GMV) alterations in PPA patients (relative to HC) are correlated with specific neurotransmitter systems. As compared to HC, voxel-based brain changes in PPA were significantly associated with spatial distribution of serotonin, dopamine, and glutamatergic pathways (p < .05, False Discovery Rate corrected-corrected). Disease severity was negatively correlated with the strength of GMV colocalization of D1 receptors (p = .035) and serotonin transporter (p = .020). Moreover, we observed a significant negative correlation between positive behavioural symptoms, as measured with Frontal Behavioural Inventory, and GMV colocalization of D1 receptors (p = .007) and serotonin transporter (p < .001). This pilot study suggests that JuSpace is a helpful tool to indirectly assess neurotransmitter deficits in neurodegenerative dementias and may provide novel insight into disease mechanisms and associated clinical features.
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