Journal of Parkinson's disease最新文献

Background and objectiveNigrostriatal dopaminergic degeneration is commonly assessed using dopamine transporter (DaT) SPECT. Iron sensitive MRI is a promising technique to assess substantia nigra, yet few studies explored its application in the prodromal stage of alpha-synucleinopathies. Here, we used susceptibility map weighted imaging (SMWI) to assess the swallow tail sign, a radiological marker for substantia nigra integrity, to detect neurodegeneration across the alpha-synucleinopathy continuum.Methods3T-MRI was performed on 115 subjects: 27 overt alpha-synucleinopathies, 34 prodromal alpha-synucleinopathies, 28 Alzheimer's disease and 26 healthy controls. SMWI was obtained with 3D multi-echo gradient-echo imaging. The presence/absence of the swallow tail sign was visually evaluated on SMWI by two neuroradiologists, blinded to the diagnosis. Swallow tail sign's visual assessment was compared across groups to investigate its sensitivity and specificity in identifying alpha-synucleinopathies. Additionally, we compared the SMWI visual analysis sign with both substantia nigra quantitative susceptibility mapping (QSM) and DaT-SPECT.ResultsThe two radiologists' inter-rater agreement was substantial (kappa = 0.8). Visual analysis showed good sensitivity (0.85) and specificity (0.82) in identifying patients with alpha-synucleinopathies. When the subjects were grouped based on DaT-SPECT results, sensitivity increased (0.92), while specificity decreased (0.74). Visual scoring was associated with quantitative substantia nigra MRI assessment obtained with QSM (p < 0.001). Lastly, subjects with the swallow tail sign rated as absent showed significantly lower (p = 0.019) uptake at DaT-SPECT (-1.857 ± 1.343) compared to those with the swallow tail sign rated as present (-0.385 ± 1.850).ConclusionsVisual analysis of SMWI swallow tail sign represents a new and reliable approach for evaluating substantia nigra neurodegeneration across the alpha-synucleinopathy continuum.

BackgroundParkinson's disease (PD) is associated with a high prevalence of cardiovascular dysfunction, a leading cause of mortality in these patients. Autonomic dysfunction, including cardiac autonomic dysfunction (CAD), is increasingly recognized as a significant non-motor symptom in PD and may contribute to adverse cardiac outcomes.ObjectiveTo investigate echocardiographic alterations in PD patients with CAD and evaluate their diagnostic utility for CAD detection.MethodsParticipants were categorized into PD-CAD and PD-nCAD groups based on Cardiovascular Autonomic Reflex Tests. Echocardiographic assessments included standard transthoracic echocardiography and two-dimensional speckle-tracking strain imaging. Multivariable regression was used to identify predictors of PD-CAD. Receiver operating characteristic curves, integrated discrimination improvementResultsA total of 78 participants were included, with a median Hoehn and Yahr stage of 2.00 [IQR 2.00, 2.50]. Among them, 33.33% were classified as having PD-CAD. Impaired systolic function characterized by decreasing left ventricular global longitudinal strain and lower systolic mitral annular velocity were found in PD-CAD group. A model combining LV-GLS, s', and LVMI predicted CAD with AUC = 0.737 (95% CI:0.624-0.850), comparable to conventional autonomic markers.ConclusionSubclinical systolic dysfunction (LV-GLS, s') reflects autonomic-mediated myocardial injury in PD and demonstrates diagnostic potential for CAD identification. Echocardiography may bridge autonomic dysfunction and cardiovascular risk in PD.

Classic accounts of 'kinesia paradoxa' typically involve highly stressful or life-threatening situations, which are difficult to translate to daily life. Here, we describe two patients with parkinsonism who successfully apply self-induced 'arousal-heightening' strategies to improve their mobility. The first patient uses an electronically modified fly swatter to self-deliver a mild electrical shock, enabling him to overcome episodes of freezing of gait. The second patient uses his phone's alarm to alert himself, resulting in improved sit-to-stand transfer. These observations suggest that self-induced arousal-heightening strategies represent a hitherto underexplored compensatory strategy that could help to improve mobility in some individuals with parkinsonism.Plain language summary titleHelping people with Parkinson's disease move more easily using alertness tricks.

BackgroundThe role of dietary factors as risk or protective factors for Parkinson's disease (PD) remains debated.ObjectiveThis retrospective case-control study aimed to evaluate the associations between foods identified through a data-driven analysis and PD, and to compare the relevance of dietary versus non-dietary factors as contributors to PD risk.MethodsThe study included 680 PD patients and 612 matched controls recruited from six Italian neurology centers. Dietary data were collected using a validated 77-item food frequency questionnaire, and factor analysis was conducted to identify groups of correlated foods (i.e., factors). Logistic regression models were used to assess the associations between these factors and PD, while non-dietary factors were subsequently included in the model for comparison.ResultsSeven factors were identified, four of which were significantly associated with PD. High consumption of sweets (Factor 1), red meat (Factor 3), and processed meats (Factor 6) was associated with an increased PD risk, whereas a high fruit intake (Factor 2) was protective. These associations remained significant after adjusting for other known non-dietary risk/protective factors. While the increased PD risk associated with dietary factors was weaker than that of non-dietary factors, protective dietary and non-dietary factors showed comparable effects in reducing PD risk.ConclusionsData-driven analysis identified foods potentially influencing PD risk, although non-dietary factors demonstrated a greater impact on PD risk. These findings highlight the need to integrate both diet and lifestyle habits into future PD research and prevention strategies.

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.

Bradykinesia and delayed step initiation are central features of Parkinson's disease (PD) and have been linked to reduced movement vigor. Evidence suggests that externally imposed urgency may upregulate vigor and improve motor speed. Previous home-based cueing interventions without time limits improved gait but failed to reduce reaction times, indicating that time constraints may be critical. We conducted a randomized controlled trial to evaluate whether time-constrained, visually guided reaching and stepping exercises enhance response speed in PD. Sixty participants with idiopathic PD (Hoehn & Yahr I-III) completed 24 supervised, home-based sessions using a set of small interactive devices that provided visual and auditory cues and recorded response times. The experimental group trained with time windows adapted during each session to maintain ∼80% success, receiving immediate success/failure feedback, while the control group performed identical tasks without time restrictions. Response times were assessed before and after training with choice stepping and reaching reaction time tasks in a laboratory setting, alongside gait and mobility tests. Repeated measures ANOVA revealed significant group × time interactions favoring the experimental group for both reaching (p < 0.05) and stepping (p < 0.001) reaction times, with medium-to-large effect sizes, whereas controls showed no change. Gait speed improved in both groups, with no additional between-group differences. These findings demonstrate that introducing temporal urgency during reactive training produces meaningful improvements in bradykinesia-related response times in individuals with PD, supporting the integration of time-constrained cueing into scalable home-based rehabilitation. ClinicalTrials.gov: NCT05829915.

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.

It is unclear whether Alzheimer disease pathology drives cognitive decline in Parkinson disease (PD) patients carrying GBA1 variants. We evaluated levels of serum phosphorylated tau 217 (p-tau217) in samples from 29 GBA1-PD, 32 idiopathic PD, 20 non-manifesting GBA1 variant carriers (GBA1-NMC) and 31 healthy controls. No differences were detected between PD groups. GBA1-NMCs showed higher levels than healthy controls, which correlated to worse cognition and subthreshold parkinsonism. Serum p-tau217 is not a marker of cognitive decline in GBA1-PD. Whether p-tau217 levels in GBA1-NMCs can predict conversion to PD or are a marker of cognitive decline, irrespective of PD, remains unknown.