Journal of Parkinson's disease最新文献

Dysphagia is a common and often underrecognized symptom in patients with Parkinson's disease (PD) that is frequently overlooked during hospitalization. Dysphagia may be present without overt clinical signs, complicating timely identification and intervention. The absence of clear guidelines for managing dysphagia in hospitalized patients with PD often results in delays in medication administration, with subsequent deterioration in both motor and non-motor symptoms. This consensus paper, developed through collaboration among experts in otolaryngology, gastroenterology, neurology, hospital medicine, nursing, social work, speech-language pathology, pharmacy, and nutrition, presents comprehensive recommendations for the evaluation and management of dysphagia in hospitalized patients with PD. These guidelines emphasize the importance of early screening, appropriate diagnostic evaluation, and multidisciplinary involvement to support timely and safe oral intake and sustained medication schedules. Special consideration is given to the role of alternative medication formulations and compensatory strategies when swallowing impairments are identified. Recognizing the variability in access to specialty care, especially in rural and community hospital settings, these recommendations also provide practical tools for providers. They outline when to initiate swallowing evaluations, criteria for specialist referral, use of telemedicine for consultations with specialists, and strategies to bridge care from the inpatient to outpatient setting. By implementing these consensus guidelines, healthcare teams can improve the safety, outcomes, and hospital experience of patients with PD, while reducing complications and length of stay associated with dysphagia-related issues.Plain language titleConsensus expert recommendations for management of swallowing difficulties in patients with Parkinson's disease during hospitalization.

IntroductionThere are conflicting findings regarding the influence of sex on idiopathic REM sleep behavior disorder (iRBD) in terms of prevalence and associated clinical characteristics. This study, conducted as part of the Italian multicenter longitudinal FARPRESTO project, aims to explore sex-related differences in the age of onset, iRBD diagnosis, and phenoconversion, as well as in cognitive and non-motor features and the occurrence of RBD-related injuries among male and female patients with iRBD.MethodsThe FARPRESTO study included 536 iRBD patients recruited from 13 Italian centers. This analysis assessed the age at iRBD diagnosis, diagnostic delay, motor and non-motor symptoms, global cognitive performance, conversion rates to neurodegenerative disorders, and the prevalence of RBD-related injuries at the time of iRBD diagnosis, stratified by sex.ResultsFemale patients were older at iRBD diagnosis compared to males (males: 67.8 years, IQR 62.5-72.6; females: 69.8 years, IQR 65.1-74.8; p = 0.003). Compared to male patients, female patients exhibited a higher prevalence of orthostatic hypotension (27.9% vs. 16.2%; p = 0.019), depression (43.9% vs. 26.6%; p = 0.010), and hallucinations (43.9% vs. 26.6%; p = 0.010) at iRBD diagnosis. Additionally, self-directed injuries were significantly more frequent in females compared to males at the first visit (71% vs. 53.2%; p = 0.034). No significant differences were observed in the phenoconversion rate between sexes.ConclusionAlthough research on sex-related differences in iRBD remains limited, this study highlights the importance of understanding sex-specific characteristics. As diagnostic and therapeutic approaches evolve, incorporating these differences will be essential for tailoring clinical strategies and improving patient outcomes.

IntroductionMetabolic covariance patterns derived from imaging data help characterize disease-related physiological changes in several neurodegenerative disorders, including Parkinson's disease (PD), but their relevance to different disease stages and/or clinical variables related to disease or disease predisposition, such as age, is often unclear.MethodsWe incorporated clinical information in deriving metabolic covariance patterns relevant to different aspects of PD: disease initiation, disease progression, and physiological similarities in PD and healthy aging. This was achieved by combining Partial Least Squares Correlation analysis with Scaled Subprofile Modeling (SSM-PLSC).ResultsWhen combining PD and HC data, SSM-PLSC identified a spatial pattern similar to the well-known PD-related disease pattern as expected; when applied to PD-only data-thus emphasizing disease progression-the spatial pattern became characterized by expanding putaminal hypermetabolism and reduced emphasis on cerebellar hypermetabolism. Finally, when applied to PD and HC data but permitting a different dependence on clinical variables, SSM-PLSC identified a spatial pattern with relative hypermetabolism in the basal ganglia, brain stem, and white matter together with relative hypometabolism in frontal cortex; in HC this pattern solely related to age, while in PD the same pattern significantly correlated with both age and disease duration.ConclusionWe identified metabolic patterns that are more closely related with different aspects of PD, directly derived from relationships between metabolic alterations and clinical variables. We also revealed metabolic signatures common to PD and aging, which may highlight age-related metabolic changes that form a predisposition to PD, as age is the single highest risk factor for PD.Plain language summary titleBrain changes in Parkinson's disease and their relationship to clinical aspects of disease.

BackgroundParkinson's disease (PD) causes disability and premature mortality if untreated. Limited access to levodopa in low- and middle-income countries leaves many patients undertreated. Mucuna pruriens (MP) is a leguminous plant that contains high concentrations of levodopa.ObjectiveTo demonstrate the non-inferiority of long-term intake of MP powder in terms of safety and efficacy compared to standard levodopa plus dopa-decarboxylase inhibitor (LD + DDCI).MethodsIn this 12-month, multicenter, randomized, open-label phase 2 trial, thirty-two untreated PD patients received levodopa monotherapy with MP powder -derived from roasted seeds without pharmacological processing- or standard LD + DDCI. Dosing was adjusted for body weight and disease stage, with MP doses further calibrated to account for the absence of a DDCI. We measured quality of life using the 39-item PD Questionnaire, motor and non-motor disability using the Movement Disorders Society updated version of the Unified PD Rating Scale (MDS-UPDRS) (parts I to IV) and the Non-Motor Symptoms Questionnaire. Safety measures included recording any adverse event and laboratory test.ResultsMP powder improved quality of life, motor and non-motor symptoms over 12 months, demonstrating similar outcome to LD + DDCI on all endpoints. Adverse events were more frequent with MP (56% vs. 37.5%, p = 0.48), though the difference was not statistically significant. Most were mild, with only 12.5% leading to discontinuation.ConclusionsMP could be a cost-effective alternative for PD individuals with limited access to commercial levodopa formulations. To confirm long-term safety and efficacy, larger international multicenter, double-blind trials with extended follow-up (e.g. 24-36 months) and ethnically diverse cohorts are needed.Registered at PACTR201611001882367.

BackgroundDespite the widespread adoption of deep brain stimulation (DBS) for treating Parkinson's disease (PD) over the last few decades, standardized post-operative care protocols remain lacking.ObjectiveThis study aimed to establish expert consensus on managing post-operative subthalamic nucleus (STN-DBS).MethodsA three-round online Delphi study was conducted involving an international panel of DBS experts actively engaged in all facets of post-operative care. In the initial round, the panel generated ideas regarding essential components of a post-operative care protocol. In rounds two and three, numerical ratings and rankings were employed to achieve consensus on the formulated statements. This iterative process culminated in a refined STN-DBS care protocol.ResultsThe study included 76 international participants who, over three survey rounds, reached consensus on 129 components of a care protocol for managing post-operative STN-DBS. The final protocol encompassed eleven essential domains: hospital discharge, rehabilitation referral, imaging and lead review, monopolar testing, local field potential sensing, troubleshooting, medication management, multiprofessional care, follow-up, empowerment of patients and caregivers, and quality control of management procedures.ConclusionsThis Delphi-based, expert-driven process resulted in a comprehensive care protocol for patients undergoing STN-DBS. The findings offer a valuable resource for healthcare professionals, providing a structured, consensus-based framework aimed at optimizing post-operative outcomes. In addition to supporting clinical practice, these recommendations may help inform policy development and drive systematic improvements in care delivery. Further research and validation in diverse clinical settings will be essential to assess the generalizability and real-world impact of the proposed procedures.

Parkinson's disease (PD) is a progressive neurodegenerative disease with multiple manifestations including both motor and non-motor symptoms. One manifestation of PD that is often overlooked is the sexual dysfunction (SD) that patients may experience. Individuals with PD can experience impairment in sexual desire, arousal or lubrication, orgasm, ejaculation, pain and the physical aspect of intimacy. This article aims to provide an overview of the current practices in the evaluation and treatment of sexual dysfunction in men in the context PD. Note that this article focuses on the male population as it reviews the available American Urology Association practice guidelines many practitioners follow, which focus on the male population. Sexual dysfunction guidelines for the female population are much more limited, and future work should review the existing literature and gaps to provide a more robust understanding of sexual dysfunction in PD. PD represents a particularly vulnerable population for development of sexual dysfunction given the multifactorial nature of its manifestations. Given its profound impact on not only the patient, but their partner, it is important to be aware of the various manifestations of SD when evaluating individuals with PD. Through thorough history taking and targeted psychosexual evaluation, we as practitioners can ensure a more holistic and comprehensive approach to caring for individuals with PD.

BackgroundCognitive dysfunction is one of the most debilitating non-motor symptoms of Parkinson's disease (PD). This study aimed to explore the interplay between altered neurotransmitter activities, including dopamine and acetylcholine, and brain metabolism in cognitive decline in PD.MethodsWe enrolled 172 PD patients (mean ± SD age 69.8 ± 8.6 years; 93 females) who underwent brain magnetic resonance imaging, N-(3-[¹⁸F]fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (¹⁸F-FP-CIT) positron emission tomography (PET), ¹⁸F-fluorodeoxyglucose (FDG) PET, and neuropsychological testing. General linear models and mediation analyses were used to investigate the association between striatal dopamine transporter (DAT) availability or basal forebrain (BF) volume, brain metabolism, and domain-specific cognitive scores.ResultsA significant relationship between caudate dopamine depletion and posterior BF atrophy was found in PD patients. Caudate and putaminal dopamine depletion were associated with altered brain metabolism in regions where PD patients showed decreased metabolism compared with healthy controls, whereas atrophy in the posterior BF was associated with hypometabolism in the lateral prefrontal, orbitofrontal, inferior parietal, and lateral temporal cortices as well as in the precuneus, with a significant interaction between caudate DAT availability and posterior BF volume. Caudate dopamine depletion was associated with visuospatial, memory, and executive dysfunction, whereas posterior BF atrophy was additionally associated with attention. Mediation analyses revealed that visuospatial dysfunction was associated with caudate dopamine depletion or posterior BF atrophy via altered brain metabolism, while executive dysfunction was linked to both directly and through metabolism changes.ConclusionsCaudate dopaminergic and posterior BF cholinergic deficits are interrelated and affect cognition in a domain-specific manner, either directly or through the mediation of altered brain metabolism.

BackgroundReactive astrocytes are one of the pathological features of Parkinson's disease (PD) and are associated with neuroinflammation and neuronal damage.ObjectiveTo explore the causal relationship between reactive astrocyte-related genes and PD through the summary data-based Mendelian randomization (SMR).MethodsWe combined these reactive astrocyte-related Quantitative Trait Loci (QTLs) data with PD genome-wide association study (GWAS) statistics. Using SMR, we explored causal links between gene expression, methylation and protein levels (pQTL) with PD, which were validated through colocalization analysis, replication cohorts and substantia nigra tissue data. The study also explored the causal relationship between DNA methylation and gene expression.ResultsSMR analysis identified 95 mQTLs (corresponding to 44 genes), 9 eQTLs, and 7 pQTLs nominally associated with PD (P-SMR_multi < 0.05 & P-SMR < 0.05, and P-HEIDI > 0.01). There was still a significant causal association between MAPK1 expression and Parkinson's disease risk after FDR correction (OR = 2.085, 95%CI = 1.463 to 2.972, P-HEIDI = 0.225, P-SMR_FDR = 0.013), supported by strong colocalization (PPH4 = 0.987). Similarly, there was a significant association between corrected CTSB protein levels and Parkinson's disease risk (OR = 0.855, 95%CI = 0.791 to 0.925, P-HEIDI = 0.076, P-SMR_FDR = 0.028). The methylation and expression of CLEC3B and PLAU were both nominally associated with the risk of PD. Further analysis revealed that there was also a causal relationship between their methylation and expression.ConclusionsWe identified the MAPK1 gene as a potential causative gene for PD. Its high expression was robustly causally associated with an increased risk of PD and was supported by strong colocalization evidence.