Clinical Parkinsonism Related Disorders最新文献

Background

Females, people with young-onset PD and older individuals, and non-white populations are historically underrepresented in clinical Parkinson’s disease (PD) research. Furthermore, research traditionally focused predominantly on motor symptoms of PD. Including a representative and diverse group of people with PD and also studying non-motor symptoms is warranted to better understand heterogeneity in PD and to generalize research findings.

Objective

This project aimed to determine whether, within a consecutive series of PD studies performed within a single center in the Netherlands: (1) the proportion of included females, mean age and proportion of native Dutch people changed over time; and 2) reports of the ethnicity of participants and the proportion of studies with non-motor outcomes changed over time.

Methods

Characteristics of participants and non-motor outcomes were analyzed using a unique dataset of summary statistics of studies with a large number of participants conducted at a single center during a 19-year period (2003–2021).

Results

Results indicate no relationship between calendar time and proportion of females (mean 39 %), mean age (66 years), proportion of studies that reported ethnicity, and proportion of native Dutch people in studies (range 97–100 %). The proportion of participants in whom non-motor symptoms were assessed increased, but this difference was consistent with chance.

Conclusion

Study participants in this center reflect the PD population in the Netherlands in terms of sex, but older individuals and non-native Dutch individuals are under-represented. We have still a lot to do in ensuring adequate representation and diversity in PD patients within our research.

Introduction

Carbidopa/levodopa enteral suspension (CLES) previously demonstrated reduction in total daily OFF from baseline by over 4 hours in advanced Parkinson’s disease patients across 54 weeks. Evidence on CLES’s long-term effectiveness on patterns of motor-symptom control throughout the day remains limited.

Methods

We present post-hoc analyses of a large, open-label study of CLES monotherapy (N = 289). Diary data recorded patients’ motor states at 30-minute intervals over 3 days at baseline and weeks 4, 12, 24, 36, and 54. Adjusted generalized linear mixed models assessed changes from baseline at each timepoint for four outcome measures: time to ON without troublesome dyskinesia (ON-woTD) after waking, motor-symptom control as measured by motor states’ durations throughout the day, number of motor-state transitions, and presence of extreme fluctuations (OFF to ON with TD).

Results

Patients demonstrated short-term (wk4) and sustained (wk54) improvement in all outcomes compared to baseline. At weeks 4 and 54, patients were more likely to reach ON-woTD over the course of their day (HR: 1.86 and 2.51, both P < 0.0001). Across 4-hour intervals throughout the day, patients also experienced increases in ON-woTD (wk4: 58–65 min; wk54: 60–78 min; all P < 0.0001) and reductions in OFF (wk4: 50–61 min; wk54: 56–68 min; all P < 0.0001). At weeks 4 and 54, patients’ motor-state transitions were reduced by about half (IRR: 0.53 and 0.49, both P < 0.0001), and fewer patients experienced extreme fluctuations (OR: 0.22 and 0.15, both P < 0.0001).

Conclusion

CLES monotherapy was associated with significant long-term reductions in motor-state fluctuations, faster time to ON-woTD upon awakening, and increased symptom control throughout the day.

Introduction

The cumulative number of patients has increased through the four waves of the pandemic in Japan. Many people experienced mental stress due to the fear of infection, and restrictions of leaving the house and leisure activities. No longitudinal study has assessed the fluctuation of neuropsychiatric symptoms during the COVID-19 pandemic using the same scale. We examined changes in non-motor symptoms, and the scores of a Parkinson’s Disease (PD)-specific questionnaire between the early and later periods during the COVID-19 pandemic.

Methods

We conducted a questionnaire survey during the first wave (from February to April 2020) and the fourth wave of the COVID-19 pandemic (from March to April 2021). We compared the number of symptoms from the two periods.

Results

Compared with the first wave, the Geriatric Depression Scale score was significantly higher in the fourth wave of the pandemic (median score of GDS: 4.00 vs. 5.50, p = 0.022). Consistently, the scores of symptoms on MDS-UPDRS part 1 in the fourth wave were significantly higher in hygiene (p = 0.033), handwriting (p = 0.033), performing hobbies and other activities (p = 0.035), and turning in bed (p = 0.046) than in the first wave.

Conclusions

Our observation over a year between the early and later phases of the COVID-19 pandemic showed an increase in the severity of depression in patients with PD.

Introduction

Motor complications (MCs) compromise therapy in many patients suffering from Parkinson’s Disease. By achieving more physiologic stimulation of dopamine-receptors, the continuous dopamine stimulation hypothesis suggests that longer-acting levodopa formulations may improve outcome. The aim of this study was to compare the duration until onset of MCs and motor disease progression in patients during their treatment initiation with either an immediate (IR) or a combined rapid- and sustained-release (i.e. dual-release; DR) levodopa formulation.

Methods

Using a sample of 69 patients, we applied time-varying survival regression analyses and linear mixed effect models to analyze the data. The latter involved preprocessing of the data to temporally align the response and predictors, including analyzing the extent of visit irregularity and potential predictors of visit intensity.

Results

This retrospective study suggests that levodopa-benserazide DR is not superior to levodopa-benserazide IR in affecting duration until MCs and disease progression. Conversely, using DR levodopa-benserazide, similar disease progression was achieved with lower and more constant doses.

Conclusions

The effects of DR levodopa-benserazide might not be strong enough to delay onset of MCs. The development of more powerful levodopa formulations remains a pressing clinical need.

Background

Computerized cognitive training may be promising to improve cognitive impairment in Parkinson’s disease and has even been suggested to delay cognitive decline. However, evidence to date is limited. The aim of this study was to assess the durability of eight-week cognitive training effects at up to two years follow-up.

Methods

One hundred and thirty-six (1 3 6) individuals with Parkinson’s disease, subjective cognitive complaints but without severe cognitive impairment (Montreal Cognitive Assessment ≥ 22) participated in this double-blind RCT. Participants underwent an eight-week home-based intervention of either adaptive, computerized cognitive training with BrainGymmer (n = 68) or an active control (n = 68). They underwent extensive neuropsychological assessment, psychiatric questionnaires and motor symptom assessment at baseline and one and two years after the intervention. We used mixed-model analyses to assess changes in cognitive function at follow-up and performed Fisher’s exact tests to assess conversion of cognitive status.

Results

There were no group differences on any neuropsychological assessment outcome at one- and two-year follow-up. Groups were equally likely to show conversion of cognitive status at follow-up. A considerable amount of assessments was missed (1y: n = 27; 2y: n = 33), most notably due to COVID-19 regulations.

Conclusions

Eight-week cognitive training did not affect long-term cognitive function in Parkinson’s disease. Future studies may focus on one cognitive subgroup to enhance reliability of study results. Intervention improvements are needed to work towards effective, lasting treatment options.

Diagnostic usefulness of the floating door sign was tested in 144 PD patients, 41 essential tremor patients and 38 controls. There were no differences in the presence of floating door sign between PD and ET patients. The sign does not seem to be a reliable differential diagnostic tool.

Introduction

Motor and nonmotor Parkinson’s disease (PD) symptoms can negatively influence employment, which may contribute to financial hardship. This article explores the association between financial hardship, employment challenges, and quality of life in people with early PD.

Methods

We measured financial hardship with a validated summary item (5-point scale, lower score - less hardship) and the Comprehensive Score for Financial Toxicity (0–44, lower score worse toxicity) in a cohort of 60 employed individuals with early PD (<5 years). We used Spearman’s Correlations and nonparametric tests to identify associations between financial hardship, demographic characteristics, PD-related factors, employment factors, and quality of life (Neuro-QOL computer adapted measures).

Results

The sample was mostly white (93 %) and male (65 %). The plurality were highly-educated with graduate degrees (42 %). Of the 60 participants, 23 (38 %) reported a little bit and 14 (23 %) reported somewhat or more hardship. Comprehensive financial toxicity (22.0 ± 8.7) was correlated moderately (ρ = −0.56) with the single-item summary score. High financial hardship was associated with reduced confidence in job retention (ρ = −0.43, p = 0.001) and reduced perceived workplace success (ρ = −0.352, p = 0.006). Financial hardship was also associated with poorer quality of life in five Neuro-QOL domains: lower extremity function, satisfaction with social roles and activities, depression, anxiety, and stigma (p < 0.05).

Conclusion

Financial hardship was common and was associated with employment challenges and poor quality of life. Further work should explore the effects of medical and psychosocial interventions to alleviate financial and employment challenges in individuals with early PD.

Background

In patients with Parkinson’s Disease (PD), two distinct motor subtypes, tremor dominant (TD) and postural instability and gait difficulty (PIGD), can be differentiated using Unified Parkinson’s Disease Rating Scale (UPDRS) sub-scores. This post hoc analysis of pooled data from eight pivotal studies examined the effect of treatment with istradefylline, a selective adenosine A_2A receptor antagonist, on these subtypes.

Methods

In eight randomized, placebo-controlled phase 2b/3 trials, patients on levodopa with carbidopa/benserazide experiencing motor complications received istradefylline (20 or 40 mg/day) or placebo for 12 or 16 weeks. TD subtype was defined by the UPDRS II/III items kinetic and postural tremor in right/left hand and (resting) tremor in the face, lips, chin, hands, or feet; PIGD items were freezing, walking, posture, gait, and postural instability. The ratio of mean scores from TD:PIGD items determined subtype (TD [TD:PIGD ratio ≥ 1.5], PIGD [TD:PIGD ratio ≤ 1.0], mixed-type [ratio 1–1.5]).

Results

In total, 2719 patients were included (PIGD, n = 2165; TD, n = 118; mixed-type, n = 188; not evaluable, n = 248). Among TD subtype patients, the least-squares mean change from baseline versus placebo in UPDRS II/III TD-related total score was significant at 20 mg/day istradefylline (−2.21; 95 % CI, −4.05 to −0.36; p = 0.02). For PIGD subtype patients, there was a significant difference from placebo in UPDRS II/III PIGD-related total score at 40 mg/day istradefylline (−0.25; −0.43 to −0.06; p = 0.01).

Conclusions

The data from this analysis of UPDRS-based motor subtypes suggest that istradefylline can improve motor disability in PD patients with motor fluctuations regardless of PD subtype. Future research should characterize the effects of istradefylline on tremor.