Journal of Parkinson's disease最新文献

BackgroundOccupational pesticide (OcP) exposure and pathogenic GBA1 variants are established risk factors for Parkinson's disease (PD). However, whether they interact to influence disease onset or severity remains uncertain.ObjectiveTo determine the prevalence of OcP exposure and other lifestyle risks in relation to GBA1 status and their interactions on age of onset (AOO) and clinical scores in a well-characterized PD cohort.MethodsWe analyzed 505 people with PD (PwP) enrolled in the Ankara Parkinson's Disease Registry (ANPAR). GBA1 variants were identified using next-generation sequencing; benign or uncertain variants were excluded. Structured, face-to-face interviews collected data on history of OcP exposure, history of head trauma, smoking, coffee and tea consumption habits. PwP with and without GBA1 variants were compared using unadjusted and adjusted tests. General linear models assessed gene-environment interactions on AOO, non-motor, and motor scores.ResultsFifty-two PwP (10.3%) carried pathogenic GBA1 variants. OcP exposure was more common in carriers than non-carriers (36% vs. 22%; adjusted OR 1.98, 95%CI: 1.07-3.67, p = 0.031). No other risk factor differed between groups. Smoking independently delayed AOO, but there were no significant GBA1 × risk/lifestyle factor interactions for AOO or for motor/non-motor scores. Head trauma, coffee, tea, and OcP exposure showed neither main nor interaction effects on severity indices.ConclusionOcP exposure is reported more often by individuals carrying pathogenic GBA1 variants, supporting a gene-environment "dual-hit" model. However, OcPs did not modify AOO or disease severity once PD was manifest.

BackgroundDespite substantial research efforts, advances in Parkinson's disease therapeutics remain largely confined to the management of motor symptoms, with comparatively limited progress in addressing non-motor features, and with no proven success in disease-modifying therapies to date.ObjectivesTo describe recent trends in Parkinson's disease therapeutic trials and to characterize the experimental compounds and targets investigated in drug development programs.MethodsWe conducted a cross-sectional analysis of Parkinson's disease therapeutic clinical trials registered in ClinicalTrials.gov, EUCTR, and CTIS since 2013. For the subset of commercially sponsored medicinal product trials, we further described therapeutic objectives and pharmacological targets.ResultsWe identified 1855 trials, of which 29% were ongoing. Commercial trials predominantly investigated drugs and devices, whereas non-commercial trials more often focused on non-pharmacological interventions. Among 294 commercial medicinal product trials, 166 distinct products representing 146 active compounds were identified, mapped to 52 pharmacological targets, with additional compounds acting through multiple or unclear mechanisms. Dopaminergic approaches dominated (dopamine receptor agents, 18%; dopamine replacement, 15%), followed by aSyn-targeted strategies (10%). Advanced therapies, including cell and gene therapies, were investigated in 8%. Motor symptoms, particularly motor fluctuations, were the most frequent objectives (45%), whereas non-motor symptoms were rarely addressed (8%).ConclusionsThe landscape of Parkinson's disease trials has expanded over the past decade, but progress has largely been limited to incremental improvements in dopaminergic therapies. The continued lack of effective treatments for non-motor symptoms and disease modification suggests a need to rethink current approaches to drug development in Parkinson's disease.

BackgroundSuicide risk in Parkinson's disease (PD) remains understudied, with limited exploration of the impact of neuropsychiatric comorbidities and commonly prescribed PD and psychiatric medications.ObjectiveTo investigate the prevalence and correlates of suicide risk in PD.MethodsThis study comprised 129 people with PD (PwP) undergoing screening for clinical trial participation at a movement disorders clinic. Suicide risk and psychiatric diagnoses were assessed with the Mini International Neuropsychiatric Interview (MINI). The Parkinson Anxiety Scale (PAS) and the Beck Depression Inventory-II (BDI-II) were also administered. Logistic regression models were used to identify correlates of suicide risk.ResultsSuicide risk was present in 22.5% of the sample, with 3.9% reporting a lifetime suicide attempt. No associations were found between suicide risk and demographic or PD-related variables. Suicide risk was independently associated with higher PAS score (odds ratio (OR) = 1.17; 95% confidence interval (CI): 1.07-1.29; p = 0.001), higher BDI-II suicidal ideation item score (OR = 32.43; 95% CI: 7.78-135.12; p < 0.001), and benzodiazepine use (OR = 13.88; 95% CI: 2.77-69.57; p = 0.001). Furthermore, the BDI-II suicidal ideation item missed nearly 45% of at-risk individuals identified by the MINI, with only 16 scoring above 0.ConclusionsDespite no documented suicide risk in participants' medical charts or neurologists' referrals, over one-fifth were found to be at risk. Correlates of suicide risk in PD warrant further investigation. This study highlights the importance of screening PwP for suicidality during routine care, and that a one-item screen might not adequately capture at-risk individuals.ClinicalTrials.gov IdentifierNCT03968133.

Compensation strategies are a key element of gait rehabilitation in Parkinson's disease, ideally requiring involvement of specialized therapists. However, access to allied healthcare is not universally guaranteed. We evaluated an online platform to deliver compensation strategies for gait in 25 individuals with Parkinson's in rural Brazil. After three weeks of use, median patient-reported impact of gait impairment on daily activities [rated on visual analogue scale, 0-10] decreased from 7 to 4 (p < 0.001), without reported falls. This suggest that the platform is a safe and effective tool for supporting gait rehabilitation in underserved communities with limited access to healthcare services.

BackgroundPatients with Parkinson's disease (PD) frequently experience a progressive decline in their activities of daily living (ADL), necessitating caregiver support. Discrepancies between patient and caregiver ADL ratings are common and may hinder optimal care.ObjectivesTo quantify patient-caregiver differences in ADL ratings and identify the clinical factors associated with these discrepancies.MethodsWe conducted a cross-sectional study involving 217 patients with PD and their primary caregivers. Both groups independently completed the Activities of Daily Living Questionnaire (ADLQ). Discrepancy (dADLQ) was defined by subtracting the caregiver-rated score from the patient-rated score; its absolute value (δADLQ) reflected the degree of disagreement. Associations with clinical variables, including motor and non-motor symptoms (cognition, mood, sleep, and autonomic function), were examined using multivariate regression.ResultsThe mean ADLQ scores were similar between patients and caregivers, but individual differences varied. The no-discrepancy group was characterized by younger age, shorter disease duration, and lower caregiver burden than those with any discrepancy. Larger δADLQ was associated with more severe motor and non-motor symptoms, as well as increased caregiver burden and depression. The dADLQ scores showed directional associations with patient mood and caregiver burden. Multivariate analysis revealed that δADLQ was independently predicted by greater motor symptom severity and gastrointestinal dysfunction.ConclusionsDiscrepancies in ADL ratings were common in patients with PD and increased with disease severity. They were associated with motor and non-motor symptoms, particularly gastrointestinal dysfunction and mood factors. These findings underscore the importance of integrating both perspectives in clinical assessment, particularly for advanced diseases.Plain language summary titleUnderstanding the Gap Between Patients with Parkinson's Disease and Their Caregivers in Daily Life Abilities.

Gut microbiome alterations are increasingly linked to Parkinson's disease (PD), yet regional signatures remain underexplored. We performed shotgun metagenomic sequencing of stool samples from Egyptian PD patients and healthy controls. PD patients exhibited depletion of short-chain fatty acid-producing taxa, and enrichment of pathobionts. Our findings suggested a pro-inflammatory gut shift in PD and emphasized the need for geographically diverse microbiome studies. While limited in sample size (n = 7 PD patients and n = 6 controls), this pilot addressed a critical gap in African PD microbiome research.

BackgroundThe needs of people with Parkinson's disease (PD) or atypical parkinsonism (AP) change significantly in the final weeks to days of life. A better understanding of this phase can help improve care.ObjectiveTo examine healthcare use and end-of-life care in people with PD.MethodsWe conducted a retrospective study (2022-2023) in three nursing homes, four hospitals, and eleven general practices in the Netherlands. Electronic health records of deceased individuals with PD or AP were reviewed for symptoms, healthcare use, and professional involvement.ResultsWe reviewed 189 records (70.4% PD; mean age 80.2; 68.1% male). In the last two weeks of life, patients had an average of 8.4 symptoms, with a higher burden in AP. Palliative sedation was used in 60.4%, most often in nursing homes (up to 78.3%) and among AP patients. Euthanasia occurred in 11 cases (6 PD, 5 AP), mainly in nursing homes and general practices. Antibiotics and pain medications were commonly used; fluid and oxygen therapy were more frequent in hospitals. Most patients were treated by a GP and 3-4 other healthcare professionals, but only 12.7% received support from a palliative care team.ConclusionsPeople with PD and AP face a high symptom burden at the end of life, yet palliative care involvement is limited. The frequent use of palliative sedation and cases of euthanasia reflect the complexity of this care phase. Better integration of palliative expertise and research into symptom management is urgently needed.

Mild cognitive impairment and dementia are common symptoms in people with Parkinson's disease (PwPD) that impair the quality of life of those affected. However, PD-specific concepts for the prevention of cognitive decline are rarely incorporated into routine care. Here, we provide key data on cognitive impairment in PwPD and a framework for primary, secondary, and tertiary prevention in this context. The importance of cognitive reserve as a protective buffer for cognitive decline in PwPD is highlighted. Relevant lifestyle and health-related factors, including cognitive aspects, physical and social activity, diet, hearing loss, and cardiovascular factors, are discussed. Evidence on the efficacy of possible cognition-enhancing interventions in PwPD-pharmacological, cognitive, physical, nutritional, and multidomain interventions-is summarized. On this basis, and the recommendations of the European Task Force for Brain Health Services, a proposal is developed outlining options for preventing cognitive impairment in PwPD that could be implemented in routine care, as well as further developments needed to achieve a best-case scenario. The main pillars of a strategic agenda for this purpose include: (i) regular assessment of cognitive state, overall risk, and risk factors for cognitive decline; (ii) risk communication and education concerning modifiable risk factors with standardized procedures; (iii) risk reduction with multi-domain interventions for secondary prevention; and (iv) cognitive enhancement with cognitive and physical training for tertiary prevention. As the proposal makes clear, the prevention of cognitive impairment in PwPD requires interdisciplinary collaboration organized throughout PD care networks.