Movement Disorders Clinical Practice最新文献

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) is an accepted therapy for Parkinson's disease (PD) with disabling motor complications. For elderly patients with poorer cognition and postural instability, GPi has been proposed as the preferable DBS target based on expert opinion, arguing GPi-DBS may be less complicated by depression, apathy, worsened verbal fluency, and executive dysfunction, resulting in greater improvement in quality of life (QoL). However, data supporting such patient-tailored approach are lacking.

Objectives: The aims were to analyze whether the DBS target influences QoL in a PD cohort and a matched subgroup of frail patients with poor cognitive status and reduced postural stability, and whether other factors affect the QoL outcomes.

Methods: In this retrospective study, we analyzed a single-center cohort of 138 PD patients who received bilateral STN-DBS (117) or GPi-DBS (21) using the mentioned approach for target selection. All patients underwent standardized clinical evaluations of motor- and nonmotor signs as well as QoL before and 1 year after surgery.

Results: DBS of both targets improved motor signs, dyskinesias, and pain. QoL improved without significant difference between the targets, but with a trend for greater improvement across all QoL domains in favor of the STN, even in an STN subgroup matched to the GPi group.

Conclusion: Our results contradict the prevailing belief that GPi-DBS is superior in frail PD patients with cognitive decline and postural instability, questioning the proposed patient-tailored approach of DBS target selection. Further studies are needed for a data-driven approach.

Background: Alpha-synucleinopathies, such as Parkinson's disease (PD), Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB), demonstrate sex differences with regard to prevalence, age of onset, and motor manifestations. Neuropsychiatric symptoms (NPS) are common early and late manifestations of these disorders.

Objectives: We aimed to describe sex differences in NPS across alpha-synucleinopathies.

Methods: We searched Web of Science Core collection databases to identify observational studies published between January 1, 2000, and June 1, 2022, reporting the prevalence or severity of NPS among individuals with a diagnosis of PD, PDD, or DLB. Prevalence and severity were pooled for each NPS according to sex using random-effects models.

Results: Two-hundred-and-forty studies, representing 796,026 participants (45% females), were included in the meta-analysis. Female sex was associated with a higher prevalence of anxiety (OR = 1.60 [95% CI: 1.40, 1.82]), depression (OR = 1.56 [1.45, 1.67]), fatigue (OR = 1.21 [1.02, 1.43]), and psychotic symptoms (OR = 1.26 [1.14, 1.40]) and more severe anxiety (g = 1.35 [95% CI: 0.58, 2.13]), depression (g = 1.57 [1.05, 2.08]), and fatigue (g = 0.86 [0.41, 1.32]), while male sex was associated with a higher prevalence of apathy (OR = 0.77 [0.63, 0.93]), impulse control disorders (OR = 0.67 [0.55, 0.82]), REM sleep behavior disorder (OR = 0.54 [0.42, 0.70]), hypersomnolence (OR = 0.67 [0.56, 0.80]), and suicide (OR = 0.30 [0.20, 0.44]).

Conclusions: NPS have different prevalences and severities in alpha-synucleinopathies according to sex. These findings support consideration of sex in the elaboration of clinical tools.

Background: Family history of Parkinson's disease (PD) is a common finding in PD patients. However, a few studies have systematically examined this aspect.

Objectives: We investigated the family history of PD patients, comparing demographic and clinical features between familial PD (fPD) and sporadic PD (sPD).

Methods: A cross-sectional study enrolling 2035 PD patients was conducted in 28 Italian centers. Clinical data and family history up to the third degree of kinship were collected.

Results: Family history of PD was determined in 21.9% of patients. fPD patients had earlier age at onset than sporadic patients. No relevant differences in the prevalence of motor and nonmotor symptoms were detected. Family history of mood disorders resulted more prevalently in the fPD group.

Conclusions: fPD was found to recur more frequently than previously reported. Family history collection beyond the core family is essential to discover disease clusters and identify novel risk factors for PD.

Background: Orthostatic hypotension (OH) is a common condition in Parkinson's disease (PD) with a possible link to cognitive decline.

Objective: The aim was to explore the association between OH and PD-associated mild cognitive impairment (PD-MCI) and dementia (PDD) over 9 years in a population-based incident PD cohort.

Methods: We prospectively followed up patients from PD diagnosis with serial blood pressure measurements, clinical examinations, and neuropsychological assessments. We defined OH using (1) consensus-based criteria and (2) clinically significant OH by mean arterial pressure (MAP) in standing position ≤75 mmHg. PD-MCI and PDD were diagnosed according to acknowledged criteria. We applied generalized estimating equations models to investigate associations between OH measurements and cognitive impairment over time. Weibull accelerated failure time regression models were used to study if early OH (≤3 years of PD diagnosis) accelerates the time to incident PD-MCI and PDD.

Results: Of 186 enrolled patients, consensus-based OH affected 68.8%, clinically significant OH 33.9%, PD-MCI 60.8%, and PDD 31.2%. Consensus-based OH was associated with PD-MCI (odds ratio [OR]: 2.04, 95% confidence interval: 1.44-2.90, P < 0.001), whereas clinically significant OH was associated with both PD-MCI (OR: 1.95, 1.11-3.43, P = 0.020) and PDD (OR: 3.66, 1.95-6.86, P < 0.001). Early clinically significant OH, but not early consensus-based OH, reduced time to incident PD-MCI by 54% (P = 0.021) and time to PDD by 44% (P = 0.003) independently of potential confounders, including supine hypertension and cardiovascular disease.

Conclusions: MAP in standing position emerged as a stronger predictor of cognitive decline than OH determined using consensus-based criteria. These findings have implications for both research and clinical practice.

Background: The dopamine transporter striatal binding ratio (DAT SBR) has been used as an outcome measure in Parkinson's disease (PD) trials of potential disease-modifying therapies; however, both patient characteristics and analysis approach potentially complicate its interpretation.

Objective: The aim was to explore how well DAT SBR reflects PD motor severity across different striatal subregions and the relationship to disease duration, and side of onset.

Methods: DAT SBR for the anterior and posterior putamen and caudate in both hemispheres was obtained using validated automated quantitative software on baseline scans of 132 patients recruited for the Exenatide PD2 and PD3 trials. Associations between mean and lateralized SBR subregions (posterior and anterior putamen and caudate) and summed and lateralized motor characteristics were explored using regression analysis. Analyses were repeated considering disease duration and limiting analysis to the less-affected hemisphere.

Results: Lateralized bradykinesia was most consistently associated with the loss of DAT uptake in the contralateral anterior putamen. There was much higher variance in the posterior putamen, and in all regions in those with longer duration disease, although bradykinesia remained robustly associated with anterior putaminal DAT uptake even in longer-duration patients. Restricting analyses to the less-affected side did not usefully reduce the variance compared to the overall cohort.

Conclusion: These data suggest that DAT SBR could be a useful biomarker in disease-modifying trials, but a focus on anterior striatal subregions and incorporating disease duration into analyses may improve its utility.

Background: Exercise has been demonstrated to result in improvements in physical function, cognition, and quality of life in People with Parkinson's (PwP) but its adoption is variable.

Objectives: To investigate exercise preferences, levels, influencing factors among a diverse Parkinson's disease (PD) population, to understand exercise adoption patterns and plan informed interventions.

Methods: A cross-sectional survey collected data through online platforms and paper-based methods. The Exercise Index (ExI) calculated exercise level based on frequency and duration.

Results: Of 2976 PwP, 40.6% exercised regularly, 38.3% occasionally, and 21.2% did not exercise. The overall mean ExI was 18.99 ± 12.37. Factors associated with high exercise levels included exercising in groups (ExI 24-26), weightlifting (ExI 27 (highest)), using muscle-building equipment (ExI 25-26), and exercising at home following an app (ExI 26). A positive trend between ExI and varied exercise groups, locations, types, and equipment was observed. No expected benefit from exercise achieved the lowest ExI (8). Having at least two exercise-promoting factors, a bachelor's degree or higher, receiving exercise advice at initial visits, and aged ≤40 years at PD onset were strong predictors of exercise (adjust OR = 7.814; 6.981; 4.170; 3.565). Falls and "other" most troublesome PD symptoms were negative predictors (aOR = 0.359; 0.466). Barriers to exercise did not predict the odds of exercise.

Conclusions: The study shows that PwP's exercise behavior is influenced by their exercise belief, age at PD onset, doctor's advice at initial visits, education level, symptoms, and exercise-promoting factors. High exercise levels were associated with certain types of exercises and exercising in groups.

Background: The Levodopa Equivalent Daily Dosage (LEDD) calculation algorithms help in capturing and harmonization of Parkinson's Disease (PD) therapies. Analyzing these updates is essential for validating their effectiveness.

Objective: To assess updated LEDD conversion factors in capturing the newer therapies in PD and therapy modules in different geographical cohorts.

Methods: Data were sourced from 10 Centers from 6 countries representing 2 different continents. The study compared the LEDD conversion factors proposed by Tomlinson et al and Jost et al, alongside investigating demographic disparities.

Results: The analysis involved 2943 subjects; 87% (n = 2577) met the UK Brain Bank criteria for PD. The LEDD differed significantly across methodologies (Tomlinson vs. Jost, 598 mg vs 610 mg, P < 0.0001). Geographical disparities highlighted variations in PD onset age (P < 0.0001). Jost and Tomlinson's calculations demonstrated consistency within but significant differences across countries (P < 0.0001).Age at onset revealed statistically significant differences in LEDD requirements (P < 0.0001), which were particularly higher in 21-50 years (718 mg vs 566 mg). This subgroup also demonstrated increased usage of non-Levodopa therapies (P < 0.0001). Men exhibited higher total LEDD (P = 0.001). 34% reported dyskinesia, associated with higher LEDD (756 mg, P < 0.0001). Surgically treated patients also had higher LEDD (P < 0.0001) and a significant difference between Jost and Tomlinson dosages (761 mg vs716mg) reflecting the incorporation of newer therapeutic molecules.

Conclusion: This analysis delineates the importance of updated LEDD algorithms and intricacies in the landscape of PD treatment, underscored by geographical, age-related, and gender-specific variations, in real-life management scenarios.