Journal of Parkinson's disease最新文献

BackgroundHigh intensity interval training (HIIT) involves vigorous intensity exercise bouts interspersed with low intensity bouts. Despite growing interest, the optimal dosage and clinical adaptability of HIIT in Parkinson's disease (PD) remain unclear. This scoping review synthesized the literature on systemic adaptations underlying HIIT in PD and developed a clinical framework while considering chronotropic incompetence, orthostatic hypotension, and disease progression.MethodsThree databases were searched for studies that incorporated HIIT interventions in PD. The Template for Intervention Description and Replication checklist was used to characterize the quality of intervention reporting.ResultsA total of 285 studies were screened, of which 10 studies were included. HIIT was administered 2-3 times/week for 30-60 min/session over 8-12 weeks. Seven studies used moderate-volume HIIT and three studies used high-volume HIIT protocols. The quality of intervention reporting was fair to good. HIIT improved cardiorespiratory fitness, motor severity, and functional mobility in PD, however, improvements were comparable to moderate intensity continuous training (MICT). HIIT may facilitate neuroplasticity by increasing brain-derived neurotrophic factor levels and dopamine transporter uptake. We recommend that HIIT programs for individuals with autonomic dysfunction use individualized heart rate targets, and perceived exertion for determining exercise intensity, and incorporate longer duration programs (>12 weeks).ConclusionHIIT is a well-tolerated intervention that may improve cardiorespiratory fitness, disease severity, and certain neurobiological markers in mild-moderate PD, with benefits similar to MICT. Larger trials comparing different HIIT volumes are needed to identify optimal exercise volume to inform individualized exercise prescription.

We comment here on the recently published paper by Ostentag et al., 2026, which examined self-reported environmental exposures in a group of patients with Parkinson's Disease (PD). Patients with GBA1-associated Parkinson's Disease (PD) were two times more likely to have been exposed to occupational pesticides compared to those with idiopathic PD, while there was no difference for any other exposure between the two groups. Combined with previous work, these findings suggest that GBA1 pathogenic variant status in combination with exposure to pesticides leads to a high risk of developing PD, and have several implications: at the genetic epidemiological level, they provide a partial explanation for the missing penetrance of GBA1 pathogenic variants; at the biological level, they suggest that the biological mechanisms of pathogenicity conferred by the genetic predisposition and the environmental exposure may converge on the same pathways, potentially involving the interplay between lysosomal and mitochondrial function; at the public health level, they suggest that exposure to even low levels of environmental toxins may be especially deleterious for genetically susceptible individuals with GBA1 pathogenic variants. Further studies are needed to verify these results using rigorous methods for exposure ascertainment, to identify the exact class of substances underlying this association and their biological mechanisms in this context, and to determine the exposure levels that could be considered safe in this vulnerable population.

BackgroundExergaming has shown benefits in Parkinson's disease (PD) rehabilitation; however, its feasibility and potential effectiveness for people with moderate to advanced PD remain unclear.ObjectiveTo assess the feasibility and potential effectiveness of a universally designed exergame program in people with moderate to advanced PD.MethodsThis evaluator-blind, parallel randomized controlled trial was conducted at four specialized PD care facilities in Japan. Fifty-six participants (Hoehn & Yahr stages III-V) were randomly assigned (1:1) to the intervention or control group. The intervention group participated in an 8-week, universally designed exergame program alongside a standardized rehabilitation program. Sessions were conducted in supervised groups and lasted 15 min, thrice a week. Acceptability was assessed with a questionnaire. Adherence was based on attendance. Safety was monitored, and session-level experience (fatigue, effort, perceived progress, enjoyment) was assessed. Predefined criteria were applied for acceptability, attendance adherence, and session-level experience. The potential effectiveness was assessed by changes in health-related quality of life (HR-QoL), motor function, cognitive function, social engagement, and loneliness.ResultsThe final analysis included 37 participants. The program was judged acceptable by 84% participants, and the attendance adherence was 99.7%. No intervention-related adverse events occurred. Acceptability, attendance adherence, and session-level experience met the prespecified criteria. Exploratory findings suggested potential effectiveness for HR-QoL and loneliness, whereas no significant changes were observed in motor or cognitive function scores.ConclusionThis pilot study supports the feasibility of our exergame program for people with moderate to advanced PD and shows its potential effectiveness for HR-QoL/loneliness.Trial RegistrationUMIN Clinical Trials Registry (UMIN-CTR), https://www.umin.ac.jp/ctr/, UMIN000054292 (registered on May 1, 2024).

BackgroundParkinson's disease is (PD) a progressive neurodegenerative disorder. This study investigated the effects of an individualized nutritional intervention based on the Ketoflex 12/3 protocol, in addition to standard medical treatment, on motor and non-motor symptoms in PD.Methods40 individuals with PD were included in the study, and participants were randomly assigned to intervention and control. All individuals were classified according to inflammatory, glycotoxic, toxic, and vascular biotypes. The intervention group was assigned a plant-rich diet with a low glycemic index, consistent with ketogenic principles, free of inflammatory effects, and including intermittent fasting. The primary endpoint was the change in motor symptoms measured by the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) from baseline to six months. Secondary endpoints included apathy (Starkstein Apathy Scale), activities of daily living (ADL/IADL), and gastrointestinal function (Bristol stool scale).ResultsCompared with the control group, the intervention group showed a significantly greater improvement in motor symptoms as measured by UPDRS-III (-11.0 vs +2.1 points from baseline to six months; p < 0.001). Significant between-group differences were also observed for secondary endpoints, including apathy (Starkstein Apathy Scale), activities of daily living (ADL/IADL), and gastrointestinal function (Bristol stool scale), all favoring the intervention group. Spearman correlation analyses revealed significant negative correlations with ADL and UPDRS-III scores, particularly in individuals with an inflammatory phenotype.ConclusionsThe findings suggest an individualized nutritional approach may contribute to improvement in both motor and non-motor symptoms in PD. Larger, multi-center trials with extended follow-up are needed.

BackgroundProteomic studies have identified cerebrospinal fluid (CSF) DOPA decarboxylase (DDC) as a promising biomarker candidate for Parkinson's disease (PD). The aim of this study was to develop an immunoassay for CSF DDC quantification and gain further insight into its potential as a biomarker for PD.MethodsWe validated our DDC immunoassay by quantifying CSF DDC levels in the Parkinson's Progression Markers Initiative cohort, including healthy controls (n = 29), dopaminergic drug-naïve PD patients (n = 27), and patients with scans without evidence for dopaminergic deficit (SWEDD) (n = 18).ResultsOur DDC assay detected elevated levels in CSF from dopaminergic drug-naïve PD patients and discriminated them against SWEDD patients and controls with high sensitivity and specificity. There was an inverse correlation between DDC levels and ioflupane-[123I]-single-photon emission computed tomography-based dopamine transporter (DaT-SPECT) striatal binding ratios (SBRs) from the putamen and caudate nucleus. CSF DDC levels demonstrated prognostic potential for Movement Disorder Society Unified Parkinson's Disease Rating Scale total score change five to eight years post-diagnosis. DDC levels were further increased at the three-year follow-up visit in PD patients and positively correlated with the L-DOPA equivalent daily dose. There was a strong correlation between the relative CSF DDC levels determined by a proprietary immune-based proximity extension assay and absolute levels determined with our assay.ConclusionsOur assay provided further insight into the potential of CSF DDC as a diagnostic and prognostic biomarker for PD. The unchanged levels in SWEDD patients and inverse correlation with DaT-SPECT SBRs suggest that CSF DDC levels are connected to dopaminergic deficit.

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.

BackgroundData-driven approaches identified Mild Motor Predominant (MMP), Intermediate (IM), and Diffuse Malignant (DM) as Parkinson's Disease (PD) subtypes with different motor and non-motor impairment at diagnosis. It remains unclear whether these subtypes remain stable over time or whether they represent distinct biological substrates. The alpha-synuclein seed amplification assay in CSF (CSF-αSyn-SAA) might provide further insights.Objectiveto evaluate the association between baseline CSF-αSyn-SAA parameters and 10-year clinical evolution of PD subtypes.Methods323 sporadic PD patients from PPMI dataset were classified as MMP, IM, or DM at baseline and 10-year follow-up based on motor, cognitive, sleep and dysautonomia features. CSF-αSyn-SAA parameters were collected at baseline using 150-h protocol. CSF Aβ1-42, tTau and pTau181, CSF and serum NfL were also considered at baseline.ResultsReaction times (T50, TTT) and area under the curve (AUC) respectively were shorter and larger in DM compared to IM/MMP. The difference in baseline amplification parameters was more evident when comparing subtypes based on 10-year clinical features (T50, η2 = 0.036; TTT, η2 = 0.031; AUC, η2 = 0.033; all p-values < 0.05) than when comparing subtypes based on baseline clinical features (T50, η2 = 0.012; TTT, η2 = 0.012; AUC, η2 = 0.013; all p < 0.05). Shorter T50 and TTT at baseline, or larger AUC, were associated with greater risk of DM versus MMP at 10-year follow-up (T50, OR = 4.1, p = 0.004; TTT, OR = 5.5, p < 0.001; AUC, OR = 3.5, p = 0.010). Aβ, Tau and NfL were similar between groups.ConclusionsBaseline CSF-αSyn-SAA parameters predicted long-term PD progression. Faster reactions were associated with a more severe 10-year PD phenotype considering motor and non-motor features.

BackgroundThe α-synuclein seed amplification assay (αS-SAA) represents a promising strategy for identifying individuals with α-synuclein pathology, empowering development of tailored Parkinson's disease (PD) therapeutics and clinical trial design.ObjectiveTo assess the αS-SAA in cerebrospinal fluid (CSF) from PD patients, non-manifesting carriers (NMCs) and non-manifesting non-carriers (NMNCs) of pathogenic GBA1 and LRRK2 variants.MethodsThis study collected phenotype data from participants in the single-center, longitudinal, natural history BEAT-PD study (TLV-0204-16), which included PD patients and high-risk individuals for whom CSF samples were collected at baseline and 2 years post baseline. Clinical assessments in high-risk individuals enabled calculation of the International Parkinson and Movement Disorder Society probability scores for prodromal PD.ResultsCSF from 98 participants was evaluated, with no differences in age or sex distribution observed between PD and NMC subgroups. All iPD (14/14) and GBA1-PD (14/14) participants were αS-SAA positive at baseline versus only 5/13 LRRK2-PD participants (p < 0.001); 44/45 participants with longitudinal follow-up-maintained baseline αS-SAA status at year 2.LRRK2-PD carriers, all who carried the G2019S variant, with and without positive αS-SAA status were similar in all phenotype characteristics, except for younger age at diagnosis among αS-SAA positive individuals (p = 0.04). Prodromal PD probability scores were higher in αS-SAA positive versus negative GBA1-NMCs (p < 0.001) and NMNCs (p < 0.001).ConclusionsIn LRRK2-PD, αS-SAA was associated with younger age of onset but not with motor or non-motor symptoms. In at-risk participants, αS-SAA-positive status was associated with probability scores for prodromal PD. Longitudinal follow up is required to test if αS-SAA-positivity predicts future conversion to clinical PD.

BackgroundThe quantitative assessment of the oculomotor system has emerged as a promising biomarker for neurodegenerative disorders. Although oculomotor impairments are commonly observed in multiple system atrophy (MSA) patients, the specific abnormalities and underlying neural structural changes remain poorly understood.ObjectivesTo explore oculomotor abnormalities and associated brain changes in MSA, evaluating their potential as biomarkers for diagnosis and disease monitoring.MethodsA total of 100 MSA patients and 50 healthy controls (HCs) were included in this study. All subjects underwent comprehensive evaluations, including clinical assessments, virtual reality (VR)-based ocular-tracking tasks and structural magnetic resonance imaging (MRI).ResultsCompared with HCs, MSA patients showed significantly impaired smooth pursuit (SP) with increased number of deviations (13.33 [29.33] vs. 5.67 [7.67], p < 0.001); reduced prosaccadic (PS) average velocity (194.80 ± 82.45 °/s vs. 263.07 ± 68.17 °/s, p < 0.001); and reduced antisaccade (AS) average velocity (165.82 ± 85.75 °/s vs. 257.05 ± 74.39 °/s, p < 0.001). A combination of PS and AS average velocities with SP number of deviations effectively distinguished MSA patients from HCs with an AUC of 0.814. PS average velocity was negatively correlated with UMSARS total scores (r = -0.354, p < 0.001), whereas AS accuracy was positively correlated with MoCA scores (r = 0.375, p = 0.001). Voxel-based morphometry revealed significant associations between these oculomotor parameters and atrophy in the cerebellum and frontal gyrus (p < 0.05, family-wise error correction).ConclusionsOur study provides comprehensive insights into the VR-based quantitative oculomotor analysis and its association with regional brain atrophy in MSA, contributing to novel biomarkers identification and therapeutic targets exploration.

Falls are a significant concern for people with Parkinson's disease (PwP), often leading to restriction of walking activities to avoid situations where falls may occur. However, limited research has explored the relationship between walking amount (i.e., daily steps) and falls, particularly how this relationship may be influenced by physical capacity (i.e., gait speed). This study aimed to address that gap. Results indicate that higher daily step counts were associated with higher fall rates in PwP with moderate physical capacity, and lower fall rates in those with high capacity. The relationship between walking and fall rates was moderated by physical capacity.