Background Hyperglycemia and diabetes mellitus have been recognized as poor prognostic factors for motor and nonmotor outcomes in patients with Parkinson’s disease (PD), although there is some controversy. In the present study, we investigated the effects of fasting plasma glucose (FPG) level on longitudinal motor and cognitive outcomes in PD patients.
Methods We included a total of 201 patients diagnosed with PD between January 2015 and January 2020. The patients were categorized based on FPG level: euglycemia (70< FPG <100 mg/dL), intermediate glycemia (100≤ FPG <126 mg/dL), and hyperglycemia (FPG ≥126 mg/dL), and longitudinal FPG trajectories were analyzed using group-based trajectory modeling. Survival analysis was conducted to determine the time until motor outcome (Hoehn and Yahr stage≥2) and the conversion from normal cognition to mild cognitive impairment.
Results Among the patients studied, 82 had euglycemia, 93 had intermediate glycemia, and 26 had hyperglycemia. Intermediate glycemia (HR 1.75, 95% CI 1.08-2.81, p=0.022) and hyperglycemia (HR 3.86, 95% CI 2.00-7.48, p<0.01) emerged as significant predictors of worsening motor symptoms. However, neither intermediate glycemia (HR 1.245, 95% CI 0.764-2.029, p=0.3789) nor hyperglycemia (HR 1.602, 95% CI 0.763-3.362, p=0.2129) demonstrated associations with longitudinal progression of cognitive impairment. Diabetes mellitus defined by self-reported medical history was not related to poor motor or cognitive impairment outcomes.
Conclusions Our results support that both impaired glucose tolerance and hyperglycemia could be associated with motor progression in PD.
Introduction
Exercise can improve both motor and non-motor symptoms in people with Parkinson’s disease (PwP), but there is an unmet need of accessible and sustainable exercise options. This study aimed to evaluate the effect, feasibility, and safety of a regularly performed live-streaming tele-exercise intervention for PwP.
Methods
A live-streaming exercise intervention was implemented twice a week for 12 weeks in PwP. We measured the motor and nonmotor scales in these patients before and after the intervention. Changes in clinical scores from baseline to post-intervention were analyzed using a paired t-test. Factors associated with improvements in clinical scales and compliance were analyzed using Pearson’s correlation analysis.
Results
56 participants were enrolled in the study. There were significant improvements in HADS-A (p = 0.007), HADS-D (p < 0.001), UPDRS part III (p < 0.001), UPDRS total (p = 0.015), H&Y stage (p = 0.027), and PFS-16 (p = 0.026) scores following intervention. Motor improvements were associated with improvements in mood symptoms and fatigue. Higher motor impairment at baseline was associated with a higher compliance rate and better composite motor and non-motor outcomes (ΔUPDRS total score) post-intervention. Overall, the 12-week tele-exercise program was feasible and safe for PwP. No adverse event was reported. Overall adherence was 60.0% in our cohort, and 83.4% were able to participate in more than half of the exercise routines.
Conclusion
The live-streaming tele-exercise intervention is a safe, feasible, and effective non-pharmacological treatment option that can alleviate fatigue and improve mood and motor symptoms in PwP.
Patients with Parkinson’s disease (PD) face a multitude of gastrointestinal (GI) symptoms, including nausea, bloating, reduced bowel movements, and difficulties with defecation. These symptoms are common and may accumulate during the course of PD but are often under-recognized and challenging to manage. Objective testing can be burdensome to patients and does not correlate well with symptoms. Effective treatment options are limited. Evidence is often based on studies in the general population, and specific evidence in PD is scarce. Upper GI dysfunction may also interfere with the pharmacological treatment of PD motor symptoms, which poses significant management challenges. Several new less invasive assessment tools and novel treatment options have emerged in recent years. The current review provides an overview and a practical approach to recognizing and diagnosing common upper and lower GI problems in PD, e.g., dyspepsia, gastroparesis, small bowel dysfunction, chronic constipation, and defecatory dysfunction. Management aspects are discussed based on the latest evidence from the PD and general populations, with insights for future research pertaining to GI dysfunction in PD.
Objective Safinamide is a selective, reversible monoamine oxidase B inhibitor with demonstrated efficacy and tolerability in placebo-controlled studies and is clinically useful for patients with motor fluctuations. This study evaluated the efficacy and safety of safinamide as a levodopa adjunct therapy in Asian patients with Parkinson’s disease.
Methods Data from 173 Asian and 371 Caucasian patients from the international Phase III SETTLE study were included in this post hoc analysis. The safinamide dose was increased from 50 mg/day to 100 mg/day if no tolerability issues occurred at week 2. The primary outcome was the change from baseline to week 24 in daily ON-time without troublesome dyskinesia (i.e., ON-time). Key secondary outcomes included changes in Unified Parkinson’s Disease Rating Scale (UPDRS) scores.
Results Safinamide significantly increased daily ON-time relative to placebo in both groups (least-squares mean: 0.83 hours, p = 0.011 [Asians]; 1.05 hours, p < 0.0001 [Caucasians]). Motor function relative to placebo (UPDRS Part III) improved significantly in Asians (-2.65 points, p = 0.012) but not Caucasians (-1.44 points, p = 0.0576). Safinamide did not worsen Dyskinesia Rating Scale scores in either subgroup, regardless of the presence or absence of dyskinesia at baseline. Dyskinesia was largely mild for Asians and moderate for Caucasians. None of the Asian patients experienced adverse events leading to treatment discontinuation.
Conclusion Safinamide as a levodopa adjunct is well tolerated and effective in reducing motor fluctuations in both Asian and Caucasian patients. Further studies to investigate the real-world effectiveness and safety of safinamide in Asia are warranted.
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Objective To investigate whether there is a link between cognitive function and motor reserve (i.e., individual capacity to cope with nigrostriatal dopamine depletion) in patients with newly diagnosed Parkinson’s disease (PD).
Methods A total of 163 patients with drug-naïve PD who underwent 18F-FP-CIT PET, brain MRI, and a detailed neuropsychological test were enrolled. We estimated individual motor reserve based on initial motor deficits and striatal dopamine depletion using a residual model. We performed correlation analyses between motor reserve estimates and cognitive composite scores. Diffusion connectometry analysis was performed to map the white matter fiber tracts, of which fractional anisotropy (FA) values were well correlated with motor reserve estimates. Additionally, Cox regression analysis was used to assess the effect of initial motor reserve on the risk of dementia conversion.
Results The motor reserve estimate was positively correlated with the composite score of the verbal memory function domain (γ = 0.246) and with the years of education (γ = 0.251). Connectometry analysis showed that FA values in the left fornix were positively correlated with the motor reserve estimate, while no fiber tracts were negatively correlated with the motor reserve estimate. Cox regression analysis demonstrated that higher motor reserve estimates tended to be associated with a lower risk of dementia conversion (hazard ratio, 0.781; 95% confidence interval, 0.576–1.058).
Conclusion The present study demonstrated that the motor reserve estimate was well correlated with verbal memory function and with white matter integrity in the left fornix, suggesting a possible link between cognition and motor reserve in patients with PD.
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Parkinson’s disease (PD) is a neurodegenerative disorder characterized by both motor and nonmotor symptoms. Although the basal ganglia is traditionally the primary brain region implicated in this disease process, this limited view ignores the roles of the cortex and cerebellum that are networked with the basal ganglia to support motor and cognitive functions. In particular, recent research has highlighted dysfunction in the supplementary motor complex (SMC) in patients with PD. Using the PubMed and Google Scholar search engines, we identified research articles using keywords pertaining to the involvement of the SMC in action sequencing impairments, temporal processing disturbances, and gait impairment in patients with PD. A review of abstracts and full-text articles was used to identify relevant articles. In this review of 63 articles, we focus on the role of the SMC in PD, highlighting anatomical and functional data to create new perspectives in understanding clinical symptoms and, potentially, new therapeutic targets. The SMC has a nuanced role in the pathophysiology of PD, with both hypo- and hyperactivation associated with various symptoms. Further studies using more standardized patient populations and functional tasks are needed to more clearly elucidate the role of this region in the pathophysiology and treatment of PD.
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Objective The aim of this study was to assess the effects of dancing (using the Feldenkrais method) on motor and non-motor symptoms, quality of life (QoL), and objective parameters of gait at the time of intervention and at the end of the 1-year study period.
Methods This was a single-arm study in which 12 subjects with Parkinson’s disease (PD) received dance intervention during a 6-month period. Objective motor scales, gait analysis, and questionnaires on non-motor symptoms were evaluated at baseline and at 3, 6, and 12 months.
Results Dance intervention decreased motor scale (Unified Parkinson’s Disease Rating Scale and Tinetti scale) scores and improved gait disturbance (gait velocity and step length) without increasing levodopa equivalent dose. Furthermore, dancing decreased non-motor scale (Non-Motor Symptoms Scale and Montgomery-Asberg Depression Rating Scale) scores and improved QoL.
Conclusion Our findings suggest that dance intervention can be a complementary management method for PD patients.
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Objective
Medication beliefs are a significant determinant of medication adherence in chronic illness. This study aimed to identify demographic, clinical, and medication-related factors associated with medication beliefs in patients with Parkinson’s disease (PD).
Methods
We used a descriptive cross-sectional design with a convenience sample of 173 PD patients who had been taking antiparkinson drugs for more than one year.
Results
The subjects who believed PD medication was more necessary had more severe illness, younger age of onset, longer illness duration, and longer duration of levodopa therapy. They had higher levels of non-motor symptoms and depression, number of medication uses, number of drugs, and levodopa equivalent dose, and they reported fluctuation of motor symptoms and dyskinesia. The subjects who used catechol-O-methyltransferase (COMT) inhibitors, dopamine agonists, amantadine, and monoamine oxidase-B (MAO-B) inhibitors had significantly higher necessity scores than those who did not use them. The subjects who had higher concerns about PD medications had higher levels of non-motor symptoms and depression. The subjects using amantadine and anticholinergics had significantly higher concern scores than those who did not use them. Positive necessity-concerns differentials were associated with severe illness, the presence of motor fluctuation and dyskinesia, and the use of COMT inhibitors. Based on stepwise multiple regression, the most significant factors influencing necessity beliefs were severe illness, followed by depression and motor fluctuation.
Conclusion
Severe illness, higher levels of depression, and motor fluctuation are independent factors influencing patients’ beliefs regarding medication necessity. Therefore, these characteristics should be considered in medication belief assessment and interventions for PD patients.
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Objective To determine the benefits of motor training on the sequence effect (SE), an essential component of bradykinesia in Parkinson’s disease (PD).
Methods Seven patients with de novo PD participated in this study. The patients performed regular pentagon drawing tests and exercises during four visits. The first two visits occurred before the start of medication, and the last two visits occurred at least six months after the start of medication. We assessed the severity of bradykinesia and SE at each visit and compared the results before and after exercise in both the de novo and treatment conditions.
Results In the de novo condition, the severity of bradykinesia significantly improved after motor training (p = 0.018), but it did not resolve and only showed a trend of improvement after treatment (p = 0.068). The severity of the SE decreased significantly in the drug-naïve condition (p = 0.028) but not after medication (p = 0.273).
Conclusion Our study suggests that regular motor training may be beneficial for the SE in PD.
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The concept of cognitive reserve (CR) in Alzheimer’s disease (AD) explains the differences between individuals in their susceptibility to AD-related pathologies. An enhanced CR may lead to less cognitive deficits despite severe pathological lesions. Parkinson’s disease (PD) is also a common neurodegenerative disease and is mainly characterized by motor dysfunction related to striatal dopaminergic depletion. The degree of motor deficits in PD is closely correlated to the degree of dopamine depletion; however, significant individual variations still exist. Therefore, we hypothesized that the presence of motor reserve (MR) in PD explains the individual differences in motor deficits despite similar levels of striatal dopamine depletion. Since 2015, we have performed a series of studies investigating MR in de novo patients with PD using the data of initial clinical presentation and dopamine transporter PET scan. In this review, we summarized the results of these published studies. In particular, some premorbid experiences (i.e., physical activity and education) and modifiable factors (i.e., body mass index and white matter hyperintensity on brain image studies) could modulate an individual’s capacity to tolerate PD pathology, which can be maintained throughout disease progression.
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Electrophysiological studies can provide objective and quantifiable assessments of movement disorders. They are useful in the diagnosis of hyperkinetic movement disorders, particularly tremors and myoclonus. The most commonly used measures are surface electromyography (sEMG), electroencephalography (EEG) and accelerometry. Frequency and coherence analyses of sEMG signals may reveal the nature of tremors and the source of the tremors. The effects of voluntary tapping, ballistic movements and weighting of the limbs can help to distinguish between organic and functional tremors. The presence of Bereitschafts-potentials and beta-band desynchronization recorded by EEG before movement onset provide strong evidence for functional movement disorders. EMG burst durations, distributions and muscle recruitment orders may identify and classify myoclonus to cortical, subcortical or spinal origins and help in the diagnosis of functional myoclonus. Organic and functional cervical dystonia can potentially be distinguished by EMG power spectral analysis. Several reflex circuits, such as the long latency reflex, blink reflex and startle reflex, can be elicited with different types of external stimuli and are useful in the assessment of myoclonus, excessive startle and stiff person syndrome. However, limitations of the tests should be recognized, and the results should be interpreted together with clinical observations.
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Objective Spontaneous motor tempo (SMT), observed in walking, tapping and clapping, tends to occur around 2 Hz. Initiating and controlling movement can be difficult for people with Parkinson’s (PWP), but studies have not identified whether PWP differ from controls in SMT. For community-based interventions, e.g. dancing, it would be helpful to know a baseline SMT to optimize the tempi of cued activities. Therefore, this study compared finger tapping (FT), toe tapping (TT) and stepping ‘on the spot’ (SS) in PWP and two groups of healthy controls [age-matched controls (AMC) and young healthy controls (YHC)], as SMT is known to change with age.
Methods Participants (PWP; n = 30, AMC; n = 23, YHC; n = 35) were asked to tap or step on the spot at a natural pace for two trials lasting 40 seconds. The central 30 seconds were averaged for analyses using mean inter-onset intervals (IOI) and coefficient of variation (CoV) to measure rate and variability respectively.
Results PWP had faster SMT than both control groups, depending on the movement modality: FT, F(2, 87) = 7.92, p < 0.01 (PWP faster than YHC); TT, F(2, 87) = 4.89, p = 0.01 (PWP faster than AMC); and SS, F(2, 77) = 3.26, p = 0.04 (PWP faster than AMC). PWP had higher CoV (more variable tapping) than AMC in FT only, F(2, 87) = 4.10, p = 0.02.
Conclusion This study provides the first direct comparison of SMT between PWP and two control groups for different types of movements. Results suggest SMT is generally faster in PWP than control groups, and more variable when measured with finger tapping compared to stepping on the spot.
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Objective Recent reports of hearing impairment in Parkinson’s disease (PD) have suggested that auditory dysfunction could be a non-motor manifestation of PD. These reports were based on observations of elderly patients for whom presbycusis may, to some extent, have contributed to hearing dysfunction. Therefore, we aimed to explore the auditory functions in younger patients with PD. Methods We conducted a case-control study in a relatively younger (< 55 years of age at study time) population of PD patients and healthy volunteers to test whether auditory dysfunction is a significant non-motor dysfunction in PD. Pure tone audiometry (PTA) and brainstem evoked response audiometry (BERA) were performed in all participants. Results None of the patients or controls reported hearing deficits. Fifty-one patients with PD and 50 healthy volunteers who were age- and gender-matched to the patients participated. PTA-detected hearing impairment was found in 64.7% of patients and 28% of controls (p < 0.001) for both low-mid and/or high frequencies. Hearing impairment was more frequent in the younger subgroups of patients than age-matched controls, while the frequency of hearing impairment was similar in older groups of subjects. BERA was not different between patients and controls. Conclusion Asymptomatic auditory dysfunction is a common non-motor manifestation of early-onset PD and more frequent in younger patients, indicating that it may be independent of aging. The mechanism underlying this dysfunction appears to be peripheral, although a central dysfunction cannot be ruled out based on the findings of this study.
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