Impaired sequence manipulation in non-demented patients with progressive supranuclear palsy.

PURPOSE: Sequential working memory is the ability to maintain and manipulate sequential information at a second time scale. Patients with progressive supranuclear palsy (PSP) or Parkinson's disease (PD) perform poorly in tests that require the flexible arrangement of thoughts or actions. This study investigated whether sequential working memory is differently impaired in patients with PSP versus PD. METHOD: Twenty-nine patients with PSP Richardson's syndrome (PSP-RS), 36 patients with PD, and 36 healthy controls (HC) completed 3 well-established neuropsychological tests, including digit span forward (DST-F), digit span backward (DST-B), and adaptive digit ordering tests (DOT-A). The DST-F required maintaining digit sequences, and the DST-B and DOT-A required maintaining and manipulating digit sequences. FINDING: The PSP-RS group scored lower than the PD and HC groups in the DST-B and DOT-A but not in the DST-F, indicating that the ability to manipulate sequences was impaired, but the maintenance ability was preserved in PSP-RS patients. Moreover, in PSP-RS, the DST-B score negatively correlated with the severity of motor symptoms. The actual levodopa dose positively correlated with the DST-B ordering cost (DST-F score vs. DST-B score). The PSP patients who took a greater dose of levodopa tended to have higher DST-B ordering cost. There was no effect of levodopa on DST-B or DOT-A in PD. CONCLUSION: These results suggested that the ability to manipulate sequence was already reduced in patients with PSP-RS and was worse than in patients with PD.

Regional nigral neuromelanin degeneration in asymptomatic leucine-rich repeat kinase 2 gene carrier using MRI.

Asymptomatic Leucine-Rich Repeat Kinase 2 Gene (LRRK2) carriers are at risk for developing Parkinson's disease (PD). We studied presymptomatic substantia nigra pars compacta (SNc) regional neurodegeneration in asymptomatic LRRK2 carriers compared to idiopathic PD patients using neuromelanin-sensitive MRI technique (NM-MRI). Fifteen asymptomatic LRRK2 carriers, 22 idiopathic PD patients, and 30 healthy controls (HCs) were scanned using NM-MRI. We computed volume and contrast-to-noise ratio (CNR) derived from the whole SNc and the sensorimotor, associative, and limbic SNc regions. An analysis of covariance was performed to explore the differences of whole and regional NM-MRI values among the groups while controlling the effect of age and sex. In whole SNc, LRRK2 had significantly lower CNR than HCs but non-significantly higher volume and CNR than PD patients, and PD patients significantly lower volume and CNR compared to HCs. Inside SNc regions, there were significant group effects for CNR in all regions and for volumes in the associative region, with a trend in the sensorimotor region but no significant changes in the limbic region. PD had reduced volume and CNR in all regions compared to HCs. Asymptomatic LRRK2 carriers showed globally decreased SNc volume and CNR suggesting early nigral neurodegeneration in these subjects at risk of developing PD.

Wearable sensor devices can automatically identify the ON-OFF status of patients with Parkinson's disease through an interpretable machine learning model.

Introduction: Accurately and objectively quantifying the clinical features of Parkinson's disease (PD) is crucial for assisting in diagnosis and guiding the formulation of treatment plans. Therefore, based on the data on multi-site motor features, this study aimed to develop an interpretable machine learning (ML) model for classifying the "OFF" and "ON" status of patients with PD, as well as to explore the motor features that are most associated with changes in clinical symptoms. Methods: We employed a support vector machine with a recursive feature elimination (SVM-RFE) algorithm to select promising motion features. Subsequently, 12 ML models were constructed based on these features, and we identified the model with the best classification performance. Then, we used the SHapley Additive exPlanations (SHAP) and the Local Interpretable Model agnostic Explanations (LIME) methods to explain the model and rank the importance of those motor features. Results: A total of 96 patients were finally included in this study. The naive Bayes (NB) model had the highest classification performance (AUC = 0.956; sensitivity = 0.8947, 95% CI 0.6686-0.9870; accuracy = 0.8421, 95% CI 0.6875-0.9398). Based on the NB model, we analyzed the importance of eight motor features toward the classification results using the SHAP algorithm. The Gait: range of motion (RoM) Shank left (L) (degrees) [Mean] might be the most important motor feature for all classification horizons. Conclusion: The symptoms of PD could be objectively quantified. By utilizing suitable motor features to construct ML models, it became possible to intelligently identify whether patients with PD were in the "ON" or "OFF" status. The variations in these motor features were significantly correlated with improvement rates in patients' quality of life. In the future, they might act as objective digital biomarkers to elucidate the changes in symptoms observed in patients with PD and might be used to assist in the diagnosis and treatment of patients with PD.

Striatal and Extrastriatal Monoaminergic Disruption in Progressive Supranuclear Palsy.

BACKGROUND: As a biomarker targeting vesicular monoamine transporter 2 (VMAT2), 18F-9-fluoropropyldihydrotetrabenazine (18F-FP-DTBZ) positron emission tomography (PET) is highly accurate in diagnosing Parkinson's disease (PD) and assessing its severity. However, evidence is insufficient in patients with progressive supranuclear palsy (PSP). OBJECTIVE: We evaluated the striatal and extrastriatal monoaminergic disruption of PSP and differences in patterns between patients with PSP, PD, and healthy controls (HCs) using 18F-FP-DTBZ PET, as well as its correlations with the clinical characteristics of PSP. METHODS: We recruited 58 patients with PSP, 23 age- and duration-matched patients with PD, as well as 17 HCs. Patients were scanned using 18F-FP-DTBZ PET/computed tomography, and images were spatially normalized and analyzed based on the volume of interest. RESULTS: VMAT2 binding differed significantly in the striatum and substantia nigra among the groups (P < 0.001). A more severe disruption in the caudate was noted in the PSP group (P < 0.001) than in the PD group. However, no differences were found in the nucleus accumbens, hippocampus, amygdala, or raphe between the PD and PSP groups. Within the PSP group, striatal VMAT2 binding was significantly associated with the fall/postural stability subscore of the PSP Rating Scale, especially in the putamen. Furthermore, VMAT2 binding was correlated with Mini-Mental State Examination or Montreal Cognitive Assessment in the hippocampus. CONCLUSIONS: Caudate disruptions showed prominent differences among the groups. VAMT2 binding in the striatum and hippocampus reflects the severity of fall/postural stability and cognition, respectively. © 2024 International Parkinson and Movement Disorder Society.

Impaired vestibular function associated with orthostatic hypotension in patients with multiple system atrophy.

BACKGROUND: Orthostatic hypotension (OH) is one of the most common symptoms in patients with multiple system atrophy (MSA). Vestibular system plays an important role in blood pressure regulation during orthostatic challenges through vestibular-sympathetic reflex. The current study aimed to investigate the relationship between vestibular function and OH in patients with MSA. METHODS: Participants with MSA, including 20 with OH (mean age, 57.55 ± 8.44 years; 7 females) and 15 without OH (mean age, 59.00 ± 8.12 years; 2 females) and 18 healthy controls (mean age, 59.03 ± 6.44 years; 8 females) were enrolled. Cervical and ocular vestibular evoked myogenic potentials (cVEMPs and oVEMPs) tests were conducted to evaluate vestibular function. RESULTS: Patients with MSA presented with significantly higher rate of absent cVEMPs (57.1% vs 11.1%, p = 0.001) and oVEMPs (25.7% vs 0, p = 0.021) than controls. MSA patients with OH showed more absent cVEMPs (75.0% vs 11.1%, Bonferroni corrected p < 0.001) and oVEMPs (40.0% vs 0, Bonferroni corrected p = 0.003) than controls. Patients with OH also showed higher rate of absent cVEMPs than those without OH (33.3%, Bonferroni corrected p = 0.014). CONCLUSIONS: Our results demonstrated that impairment of vestibular function was associated with MSA, particularly in those with OH. Absent VEMPs may be a potential marker for MSA severity. Our findings suggest that impaired vestibular function is involved in OH development and may serve as an intervention target.

Potential role of APOE ɛ4 allele as a modifier for the association of BDNF Val66Met polymorphisms and cognitive impairment in community-dwelling older adults.

Objective: To determine whether the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with cognitive impairment (CI) in community-dwelling Chinese older adults, and to investigate whether this relationship is modified by the Apolipoprotein E (APOE) ɛ4 allele. Methods: The study is a secondary analysis of 703 participants aged ≥60 years randomly enrolled from the Beijing Longitudinal Study of Aging II prospective cohort. The education-adjusted Mini-Mental State Examination and the Clinical Dementia Rating Scale were used to measure the cognitive performance of the subjects. The main effects and interactions (additive and multiplicative) of the BDNF Met and the APOE ε4 alleles on CI were estimated by logistic regression models. Results: In total, 84 out of 703 older adults aged ≥60 years old had CI. No significant difference was observed in the risk of CI between participants with the BDNF Met allele and that of subjects without the BDNF Met allele (p = 0.213; p = 0.164). Individuals carrying both the BDNF Met and APOE ε4 alleles had an almost 1.5-fold increased odds of CI compared with carriers of the BDNF Met allele but without the APOE ε4 allele. The additive association indicated a positive interaction of both BDNF Met and APOE ε4 alleles with wide CIs (p = 0.021; p = 0.018). Conclusion: The results suggest that the APOE ε4 allele may be a potential modifier for the association of the BDNF Val66Met polymorphism with CI in community-dwelling older adults.

Reorganization of intrinsic functional connectivity in early-stage Parkinson's disease patients with probable REM sleep behavior disorder.

REM sleep behavior disorder (RBD) symptoms in Parkinson's disease (PD) suggest both a clinically and pathologically malignant subtype. However, whether RBD symptoms are associated with alterations in the organization of whole-brain intrinsic functional networks in PD, especially at early disease stages, remains unclear. Here we use resting-state functional MRI, coupled with graph-theoretical approaches and network-based statistics analyses, and validated with large-scale network analyses, to characterize functional brain networks and their relationship with clinical measures in early PD patients with probable RBD (PD+pRBD), early PD patients without probable RBD (PD-pRBD) and healthy controls. Thirty-six PD+pRBD, 57 PD-pRBD and 71 healthy controls were included in the final analyses. The PD+pRBD group demonstrated decreased global efficiency (t = -2.036, P = 0.0432) compared to PD-pRBD, and decreased network efficiency, as well as comprehensively disrupted nodal efficiency and whole-brain networks (all eight networks, but especially in the sensorimotor, default mode and visual networks) compared to healthy controls. The PD-pRBD group showed decreased nodal degree in right ventral frontal cortex and more affected edges in the frontoparietal and ventral attention networks compared to healthy controls. Furthermore, the assortativity coefficient was negatively correlated with Montreal cognitive assessment scores in the PD+pRBD group (r = -0.365, P = 0.026, d = 0.154). The observation of altered whole-brain functional networks and its correlation with cognitive function in PD+pRBD suggest reorganization of the intrinsic functional connectivity to maintain the brain function in the early stage of the disease. Future longitudinal studies following these alterations along disease progression are warranted.

18F-FP-DTBZ PET/CT detectable associations between monoaminergic depletion in the putamen with rigidity and the pallidus with tremor in Parkinson's disease.

INTRODUCTION: The motor subtypes of Parkinson's disease (PD) are widely accepted and implemented. However, the motor subtypes have been thought to represent different stages of PD recently because some patients experience tremor-dominant (TD) conversion to the non-tremor-dominant subtype, such as postural instability-gait difficulty (PIGD). In this study, we explore the monoaminergic denervation features of the striatal and extra-striatal areas in patients with different subtypes of PD with 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-FP-DTBZ) PET/CT. METHODS: Sixty-five patients diagnosed with PD were included and classified as TD (n = 25) and PIGD (n = 40). We evaluated the difference of monoaminergic features of each subregion of brain between motor subtypes of PD, as well as associations between these features and Parkinsonian motor symptoms. RESULTS: The striatal standardized uptake value ratios (SUVR) showed that dopaminergic disruption of patients with PIGD was more symmetrical in the posterior ventral putamen (p < 0.001) and more severe in the ipsilateral posterior dorsal putamen (p < 0.001 corrected) compared with that of patients with TD. The severity of PIGD scores was associated with striatal dopaminergic depletion, while tremor was associated with monoaminergic changes in extra-striatal areas, including pallidus, thalamus, and raphe nuclie. CONCLUSION: These results indicate that patients with different motor subtypes may have different underlying mechanisms of PD pathogenesis. Therefore, accurate diagnosis of PD subtypes can aid prognosis evaluation and treatment decision-making.

Detection and prediction of freezing of gait with wearable sensors in Parkinson's disease.

Freezing of gait (FoG) is one of the most distressing symptoms of Parkinson's Disease (PD), commonly occurring in patients at middle and late stages of the disease. Automatic and accurate FoG detection and prediction have emerged as a promising tool for long-term monitoring of PD and implementation of gait assistance systems. This paper reviews the recent development of FoG detection and prediction using wearable sensors, with attention on identifying knowledge gaps that need to be filled in future research. This review searched the PubMed and Web of Science databases to collect studies that detect or predict FoG with wearable sensors. After screening, 89 of 270 articles were included. The data description, extracted features, detection/prediction methods, and classification performance were extracted from the articles. As the number of papers of this area is increasing, the performance has been steadily improved. However, small datasets and inconsistent evaluation processes still hinder the application of FoG detection and prediction with wearable sensors in clinical practice.

Population pharmacokinetics of rotigotine extended-release microspheres for intramuscular injection in patients with early-stage Parkinson's disease.

AIMS: Rotigotine extended-release microspheres is a weekly intramuscular injection formulation to treat Parkinson's disease. This study aimed to develop a population pharmacokinetics (PK) model for rotigotine extended-release microspheres to investigate its PK ethnic differences. METHODS: Data for the study were obtained from three studies in China, Japan and the US. The population PK model was developed using the Phoenix NLME 8.3.5 software. Two parallel absorption models were created to include both zero- and first-order absorptions. The elimination phase was evaluated for one- and two-compartment linear models. Moreover, covariates including sex, body weight, body mass index, albumin, creatinine clearance and race were input into the model using a stepwise covariate method. RESULTS: We constructed a one-compartment linear model with the first parallel absorption model identified as the best-fitting model. Simulation results in patients with lighter body weight (45 kg) exhibited a 27% increase in Cmax,ss and a 31% increase in AUCtau,ss compared to those with median body weight (65 kg). Patients with heavier body weight (103 kg) showed a 27% decrease in Cmax,ss and a 29% decrease in AUCtau,ss compared to the median body weight group. Asian patients displayed only a 21% increase in Cmax,ss and a 6% increase in AUCtau,ss compared to non-Asian. While we could not fully conclude that race does not affect rotigotine exposure, dosage adjustments based on race were not deemed necessary. CONCLUSIONS: Exposure differences were mainly attributed to body weight, while dose adjustments were not needed for patients of different racial identities.

New horizons in Parkinson's disease in older populations.

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. Ageing is considered to be the greatest risk factor for PD, with a complex interplay between genetics and the environment. With population ageing, the prevalence of PD is expected to escalate worldwide; thus, it is of utmost importance to reduce the burden of PD. To date, there are no therapies to cure the disease, and current treatment strategies focus on the management of symptoms. Older adults often have multiple chronic diseases and geriatric syndromes, which further complicates the management of PD. Healthcare systems and care models necessary to address the broad needs of older PD patients are largely unavailable. In this New Horizon article, we discuss various aspects of PD from an ageing perspective, including disease management. We highlight recent advancements in PD therapies and discuss new care models with the potential to improve patient's quality of life.

Smaller and Denser Speech Graphs in Nondemented Patients with Progressive Supranuclear Palsy.

The well-established semantic fluency test measures the ability to produce a sequence of spoken words from a particular category within a limited period of time. Like patients with Parkinson's disease (PD), patients with progressive supranuclear palsy (PSP) tend to produce fewer correct words than age-matched healthy adults. This study further examined the difference between patients with PSP and PD in their semantic fluency performance using a graph theory-based approach. Twenty-nine patients with PSP Richardson's syndrome (PSP-RS), thirty-eight patients with PD, and fifty-one healthy controls (HC) were recruited. All participants completed a standard semantic fluency test (animals). Their verbal responses were recorded, transcripted, and transformed into directed speech graphs. The speech graphs of the PSP-RS group showed higher density, shorter diameter, and shorter average shortest path than those of the PD and HC groups. It indicates that the PSP-RS group produced smaller and denser speech graphs than the PD and HC groups. In the PSP-RS group, moreover, the average shortest paths of the speech graphs correlated with the severity of motor symptoms. This study shows the potential of the graph theory-based approach in distinguishing the semantic fluency performance of nondemented patients with PSP-RS and PD.

A large survey on COVID-19 vaccination in patients with Parkinson's disease and healthy population.

BACKGROUND: A full rollout of COVID-19 vaccination offers the most promising prospect of bringing the pandemic to an end. This study aimed to compare the coverage, safety, and confidence of COVID-19 vaccination between patients with Parkinson's disease (PD) and healthy individuals so as to give suggestions for future immunization programs. METHODS: A web-based, nationwide, multicenter survey was carried out in China from 2021 to 2022. The age and sex-standardized vaccination rate was calculated. Multivariate stepwise logistic regression models were used to estimate the influencing factors of vaccination status. We also investigated vaccination safety, willingness, confidence, and reasons for hesitancy with some ad hoc questions. RESULTS: A total of 962 PD patients and 1208 healthy individuals participated in this survey with a vaccination rate of 71.1% vs 94.4% respectively. PD patients living in first-tier cities, with comorbidities, experiencing unstable PD with a longer course and levodopa use were less likely to get vaccinated, while healthy individuals living in first-tier cities and feeling physically poor exhibited a lower vaccination rate. For PD patients, concern about the adverse impact on existing illness and disagreement from doctors were the most common reasons for vaccination hesitancy. Whereas, no evidence was present that they experienced any local or systematic adverse events more frequently or seriously than healthy individuals, or their state of PD and comorbidities was seriously exacerbated after vaccination. A prominent transition from a little concerned to unconcerned about the security and efficacy of vaccines was evident among both two populations from pre-vaccination to post-vaccination. CONCLUSIONS: The COVID-19 vaccination rate was remarkably lower in PD patients than healthy individuals in China. The approved vaccines have shown an acceptable safety profile. Our findings would offer a reference to guide future clinical decision-making of COVID-19 vaccination and improve the immunization management of PD patients.

Homogeneous-Multiset-CCA-Based Brain Covariation and Contravariance Connectivity Network Modeling.

Brain connectivity networks based on functional magnetic resonance imaging (fMRI) have expanded our understanding of brain functions in both healthy and diseased states. However, most current studies construct connectivity networks using averaged regional time courses with the strong assumption that the activities of voxels contained in each brain region are similar, ignoring their possible variations. Additionally, pairwise correlation analysis is often adopted with more attention to positive relationships, while joint interactions at the network level as well as anti-correlations are less investigated. In this paper, to provide a new strategy for regional activity representation and brain connectivity modeling, a novel homogeneous multiset canonical correlation analysis (HMCCA) model is proposed, which enforces sign constraints on the weights of voxels to guarantee homogeneity within each brain region. It is capable of obtaining regional representative signals and constructing covariation and contravariance networks simultaneously, at both group and subject levels. Validations on two sessions of fMRI data verified its reproducibility and reliability when dealing with brain connectivity networks. Further experiments on subjects with and without Parkinson's disease (PD) revealed significant alterations in brain connectivity patterns, which were further associated with clinical scores and demonstrated superior prediction ability, indicating its potential in clinical practice.

The mechanism of impaired delayed recall verbal memory function in Parkinson's disease with orthostatic hypotension: a multiple imaging study.

Introduction: Orthostatic hypotension (OH) frequently accompanies autonomic dysfunction and is an important risk factor for cognitive impairment in Parkinson's disease (PD). However, the association between different cognitive functions and OH in PD patients is not yet fully understood. Methods: This study aimed to evaluate the scores of different cognitive domains and multiple parameters using different imaging techniques on PD patients with or without OH. A total number of 31 PD patients with OH (n = 20) and without OH (n = 11) were recruited from the Department of Neurology, Beijing Xuanwu Hospital for this study. All patients underwent beat-to-beat non-invasive blood pressure recordings and an active standing test to evaluate neurogenic OH and a global neuropsychological test to assess cognitive function. All patients underwent dynamic cerebral autoregulation (dCA) measurement, brain magnetic resonance imaging (MRI), and brain 18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Results: The results showed that OH patients had poor delayed recall verbal memory when compared with the PD patients without OH (1.75 ± 1.59 vs. 3.10 ± 1.73, p = 0.042). The dCA test indicated a significant difference in the right very low-frequency (VLF) gain between two groups (1.27 ± 0.17 vs. 1.10 ± 0.26, p = 0.045) and the brain 18F-FDG PET/CT indicated a significant difference in the SUV (right medial temporal lobe) to SUV (occipital lobe) ratio (0.60 ± 0.08 vs. 0.67 ± 0.11, p = 0.049). Meanwhile, these two imaging parameters were negatively correlated (p < 0.001). Furthermore, the score of a delayed recall verbal memory in the OH group was positively correlated with the right medial temporal lobe to occipital lobe ratio (p < 0.001) and was negatively correlated with the right VLF gain (p = 0.023). Discussion: PD with OH patients had poor delayed recall memory, which might have been caused by the decreased metabolic dysfunction of specific medial temporal lobe due to the impaired dCA ability.

Investigation of rhodamine derivative on behavioral impairment in a double neurotoxin lesion of substantia nigra and locus coeruleus dysfunctional mice.

Although multiple mechanisms have been studied, there is still a lack of effective treatment on non-motor symptoms in Parkinson's disease (PD) patients. Therapeutic effects of 5-(4-hydroxy-3-dimethoxybenzylidene)-thiazolidinone (RD-1), one of rhodamine derivatives, on motor recovery have been previously demonstrated, but its effects on non-motor symptoms remain unclear. Herein, we explored the beneficial effects of RD-1 on PD-related non-motor symptoms and changes in synaptic plasticity in the mesencephalon. To investigate its therapeutic effects in the non-motor symptoms of Parkinsonian model, we employed male C57BL/6N mice and double injection with noradrenergic specific neurotoxin N-2-Chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride, followed 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Next, we performed behavioral tests, histological analyses and immunoblotting. Our findings showed that RD-1 significantly alleviated locomotor abnormality, motor disturbance, anxiety/depression-like behavior and memory deficit. It rescued the levels of tyrosine hydroxylase in substantia nigra, and striatum. Moreover, RD-1 upregulated expression levels of α-synuclein, synapsin II, postsynaptic density 95 and vesicle-associated membrane protein 2. The restoration of synaptic function may underlie the neuroprotective effects of RD-1 in double lesioned mice, confirming its protective effect for dopaminergic neurodegeneration.

Evaluation of Nocturnal Symptoms in Chinese Parkinson's Disease Patients Based on the PDSS-2 Scale: A Multicenter Cross-Sectional Study.

BACKGROUND: Nocturnal symptoms have a significant effect on the quality of life in Parkinson's disease (PD) patients. OBJECTIVE: This study aimed to investigate the prevalence and associated factors of nocturnal symptoms in Chinese PD patients. METHODS: This multicenter cross-sectional study included 1,500 patients with primary PD from 18 centers in China was carried out between February 2019 and February 2020. Questionnaires including Parkinson's disease sleep scale 2 (PDSS-2), Parkinson's disease questionnaire 8 (PDQ-8), Beck depression inventory (BDI), and generalized anxiety disorder scale 7 (GAD-7) were used to assess nocturnal symptoms, quality of life, depression, and anxiety. RESULTS: Among 1,500 Chinese PD patients, 576 (38.4%) reported nocturnal symptoms. Of them, 59.2% were older than 65 years. The PDQ-8 total score was higher in patients with nocturnal symptoms (p < 0.01). Moderate and severe depression was reported more often in patients with nocturnal symptoms (p < 0.01), and the occurrence and severity of anxiety were higher as well (p < 0.01). Longer disease duration and higher Hoehn-Yahr (HY) stage were independently associated with nocturnal symptoms (p < 0.01). Education level, depression, disease course, HY stage, and nocturnal symptoms were related to the quality of life in Chinese PD patients (p < 0.01). CONCLUSION: Our study found that 38.4% of Chinese PD patients have nocturnal symptoms, even in early and mid-stage PD. Nocturnal symptoms were associated with worse quality of life and higher incidences of depression and anxiety. Nocturnal symptoms should be included in the assessment and care plan, especially in patients with longer disease courses and higher HY stages.

Effects of different levodopa doses on blood pressure in older patients with early and middle stages of Parkinson's disease.

Objective: Levodopa is the first-line treatment for patients with Parkinson's disease (PD). However, only a few studies have focused on the tolerance of this drug in older patients with PD in the early and middle stages. Therefore, this study aimed to explore the effects of different levodopa doses on blood pressure (BP) in this subpopulation. Methods: This cohort analysis enrolled 83 patients. The levodopa challenge test was used to evaluate drug responsiveness. After at least 12 h following anti-PD drug discontinuation, patients' BPs were measured in a lying position, after 1 min standing, and after 3 min standing, in "off state" and best "on state." Results: BP in the 250 mg and 375 mg levodopa/benserazide groups decreased significantly in the lying and standing positions. The 3-min standing-position systolic BP was significantly influenced by the dose of levodopa/benserazide. However, no statistical change was observed in the 125 mg group. The postural-mediated systolic BP disparity was significant at 3 min in the upright position. Nineteen (incidence, 22.9%) and Twenty-five patients (incidence, 30.1%) developed complications of orthostatic hypotension (OH) in the "off state" and best "on state," respectively. Mild cognitive impairment was a risk factor for OH occurrence in the "off state." The OH occurrence in the best "on state" was associated with OH in the "off state" and urinary incontinence. Conclusion: Our findings suggest that 250 mg or more of levodopa/benserazide could significantly reduce BP and orthostatic effect in older patients with PD in the early and middle stages. Therefore, they should routinely monitor their BP. Trial registration number: ChiCTR2200055707.