Journal Of Parkinson's Disease[JOURNAL]
Sun
200 papers
A monoclonal antibody-based immunoassay reinforces DOPA decarboxylase in cerebrospinal fluid as a diagnostic biomarker for Parkinson's disease with potential prognostic value.
Aviolat H, Mollon J, Giaisi S … +2 more , Barghorn S, Heym RG
J Parkinsons Dis · 2026 Mar · PMID 41693316 · Publisher ↗
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...
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.
A prospective analysis of falls in Parkinson's disease: Does physical capacity moderate the relationship between walking amount and falls rates?
Mc Ardle R, Alcock L, Hunter H … +8 more , Galna B, Godfrey A, Lawson RA, Del Din S, Yarnall A, Klenk J, Rochester L, ICICLE-Gait team
J Parkinsons Dis · 2026 Mar · PMID 41686749 · Publisher ↗
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 relation...
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.
Exercise-Induced modulation of molecular-enriched functional connectivity in Parkinson's disease.
Reimers E, Bevington C, Hanania JU … +6 more , Dhaliwal S, McKenzie J, Stein R, Liu-Ambrose T, Stoessl AJ, Sossi V
J Parkinsons Dis · 2026 Mar · PMID 41677133 · Publisher ↗
Parkinson's disease (PD) involves degeneration of dopaminergic neurons and dysfunction across multiple neurotransmitter systems, contributing to both motor and cognitive impairments. Aerobic exercise improves clinical ou...
Parkinson's disease (PD) involves degeneration of dopaminergic neurons and dysfunction across multiple neurotransmitter systems, contributing to both motor and cognitive impairments. Aerobic exercise improves clinical outcomes; however, its underlying neural mechanisms remain unclear. Using conventional resting-state fMRI combined with Receptor-Enriched Analysis of functional Connectivity by Targets (REACT), we examined molecular-enriched motor network changes following six months of supervised aerobic training in PD. Exercise-related connectivity changes were inversely correlated with baseline PD-healthy control differences, reflecting a partial normalization of PD-altered motor networks. Molecular-enriched analyses revealed selective effects on dopaminergic (FDOPA-enriched) and cholinergic (VAChT-enriched) related networks, with no changes observed in networks associated with serotonergic or noradrenergic systems. These findings provide supporting evidence for potential mechanistic links between aerobic exercise and network reorganization in PD, highlight multisystem effects, and illustrate the utility of molecular-enriched fMRI for probing neurotransmitter-specific interventions.
A personalized plant-rich, time-restricted nutritional intervention for motor and non-motor symptoms in Parkinson's disease: A randomized controlled trial.
Tağraf B, Oğul ÖE, Yerlikaya D … +1 more , Hanoğlu L
J Parkinsons Dis · 2026 Mar · PMID 41666212 · Publisher ↗
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 standa...
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.
Pharmacological inhibition of O-GlcNAcase reduces pS129-α-synuclein positive aggregates in the substantia nigra of mThy1-hSNCA mice.
Yue J, Jones B, Tran KH … +8 more , Deen M, Holicek V, Cheng WH, Michalik M, Power S, Wellington CL, Watson NV, Vocadlo DJ
J Parkinsons Dis · 2026 Mar · PMID 41666126 · Publisher ↗
BackgroundThe aggregation and spread of α-synuclein within brain are associated with the loss of dopaminergic neurons and the formation of Lewy bodies as seen in Parkinson's disease. Blocking the initiation of α-synuclei...
BackgroundThe aggregation and spread of α-synuclein within brain are associated with the loss of dopaminergic neurons and the formation of Lewy bodies as seen in Parkinson's disease. Blocking the initiation of α-synuclein aggregation, or the spread of such aggregates, may offer disease-modifying approaches to slow disease progression. Previous studies have demonstrated that modification of aggregation prone proteins, including α-synuclein, with O-linked β--acetylglucosamine (O-GlcNAc) reduces their aggregation. Small molecule inhibitors of the enzyme O-GlcNAcase (OGA), which removes O-GlcNAc from proteins, confers neuroprotective benefits in various preclinical disease models of Alzheimer's and Parkinson's diseases.ObjectiveThis study investigates the effects of long-term pharmacological enhancement of O-GlcNAcylation in a transgenic mouse model of Parkinson's disease overexpressing human α-synuclein.MethodsThiamet-G was orally administered to mThy1-hSNCA and wild-type (WT) mice for ten months. Behavioral assessments were conducted to examine changes in locomotion and cognition. Histological analyses were performed to analyze α-synuclein aggregates and dopaminergic neurons in brain sections. Immunoblot and ELISA analyses were performed to analyze O-GlcNAc and soluble α-synuclein using brain lysates, respectively.ResultsThiamet-G increased the level of O-GlcNAc in the brain of both mThy1-hSNCA and WT mice. The levels of total α-synuclein in the brain were unaltered. However, Thiamet-G strongly attenuated the deposition of pS129-immunoreactive α-synuclein aggregates within the substantia nigra, prior to observable neurodegeneration. Thiamet-G also protected against locomotor decline.ConclusionsThese results support OGA inhibition as a therapeutic approach to block the pathological formation of toxic α-synuclein as a disease-modifying treatment against Parkinson's disease.
Evolution of disease modifying therapy clinical trial design and therapeutic endpoints for Parkinson's disease.
Foltynie T, Gandhi S, Carroll C
J Parkinsons Dis · 2026 Feb · PMID 41656560 · Publisher ↗
The traditional approach of using double-blind, placebo controlled, parallel group trial designs has confirmed the efficacy of a large number of agents in relieving the symptoms of Parkinson's disease (PD) but has not, t...
The traditional approach of using double-blind, placebo controlled, parallel group trial designs has confirmed the efficacy of a large number of agents in relieving the symptoms of Parkinson's disease (PD) but has not, to date, led to the discovery of any disease-modifying treatments for PD. There are multiple potential reasons underlying the failure to find disease modifying approaches, which may in part relate to; inadequate understanding of PD pathophysiology and therefore inappropriate target selection; the possibility that even good candidate drugs may simply fail to reach and to ultimately engage with their putative targets at the required dose; and the significant heterogeneity of the disease both in terms of its pathophysiology and its motor and non-motor symptoms. PD also has some additional challenges that may be addressed by careful consideration of trial design. This includes; its generally slow rate of disease progression necessitating long follow-up times to identify evidence of disease slowing; lack of understanding regarding the optimal stage of disease that might be most amenable to intervention; as well as lack of consensus regarding which outcome measures best capture patient relevant disease progression, and which biomarkers might consistently and objectively provide the earliest indication of disease progression. In this review we will discuss these issues and potential approaches that may help in the evolution of clinical trial design and thus ultimately provide a pathway to increase the likelihood of successful identification of disease-modifying treatments for Parkinson's disease.
Can transcranial Direct Current Stimulation enhance the efficacy of a rehabilitative intervention for the treatment of Freezing of Gait in Parkinson's disease? A double-blind, randomized controlled study.
Madrid J, Batzianouli E, Rutz D … +3 more , Voisard S, Van den Keybus K, Benninger DH
J Parkinsons Dis · 2026 Mar · PMID 41637203 · Publisher ↗
BackgroundFreezing of gait (FOG) in Parkinson's disease (PD) is a major cause of disability and falls and often responds incompletely to conventional therapy. Rehabilitative interventions including cognitive strategies a...
BackgroundFreezing of gait (FOG) in Parkinson's disease (PD) is a major cause of disability and falls and often responds incompletely to conventional therapy. Rehabilitative interventions including cognitive strategies and sensory cueing are efficacious, but difficulties in learning impair executing these strategies. Transcranial direct current stimulation (tDCS) enhances motor task learning and might enhance the efficacy of rehabilitative interventions.ObjectiveWe assessed whether tDCS can enhance the efficacy of physiotherapy for FOG in PD.MethodsIn a randomized, double-blind, controlled study, anodal tDCS (pre-/motor cortex) or sham-tDCS were delivered combined with a standardized rehabilitative intervention in 24 PD patients with FOG for eight sessions within four weeks. Clinical assessment included walking a Parcourse, timed gait tests, FOG questionary, and clinical scales at baseline, across the interventions with a follow-up 3-months after the last intervention.ResultsNineteen PD patients with FOG completed the study. TDCS combined with physiotherapy reduced FOG, but not more than physiotherapy aloneConclusionCombining tDCS with physiotherapy did not enhance its efficacy in reducing FOG.
Feasibility and potential effectiveness of an exergame program for people with moderate to advanced Parkinson's disease: A pilot randomized controlled trial.
Matsushita W, Nagaki K, Takashi N … +3 more , Ohtera S, Ohara C, Takahashi M
J Parkinsons Dis · 2026 Mar · PMID 41637155 · Publisher ↗
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 feasi...
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 Registration, https://www.umin.ac.jp/ctr/, (registered on May 1, 2024).
A randomized safety and feasibility crossover trial of two Mediterranean-ketogenic interventions in individuals with Parkinson's disease.
Tosefsky K, Lam JS, Wang YN … +8 more , Keymanesh S, Kuan AJ, Metcalfe-Roach A, Cirstea MS, Sacheli MA, Brett Finlay B, Cohen TR, Appel-Cresswell S
J Parkinsons Dis · 2026 Mar · PMID 41637153 · Publisher ↗
BackgroundBoth Mediterranean and ketogenic diets have been proposed as nutritional interventions in Parkinson's disease (PD). Combined approaches may offer maximal benefits.ObjectiveAssess the feasibility, safety and exp...
BackgroundBoth Mediterranean and ketogenic diets have been proposed as nutritional interventions in Parkinson's disease (PD). Combined approaches may offer maximal benefits.ObjectiveAssess the feasibility, safety and exploratory efficacy of two ketogenic interventions, using a Mediterranean diet base, in individuals with PD (PwP).MethodsIn this Phase II, random-order crossover study, PwP followed two 8-week dietary interventions, separated by an 8-week washout: 1) a high-fat, low-carbohydrate Mediterranean diet (MeDi-KD) and 2) a standard Mediterranean diet supplemented with medium chain triglycerides (MeDi-MCT).ResultsOf 52 participants randomized, 48 started the trial. Forty-one (79%) participants completed at least one, whereas only 33 (63%) completed both intervention phases. There were no intervention-related serious adverse events, nor any significant changes in plasma lipid profiles. Seventy-three percent and 92% of participants reported deviating from the MeDi-KD and MeDi-MCT no more than a few times per month, respectively. Moderate Mediterranean Diet Adherence Screener scores of 6.7 (SD: 1.6) and 7.2 (SD: 2.3) were achieved during the MeDi-KD and MeDi-MCT, respectively, out of a maximum of 14. Fifty percent of participants were in nutritional ketosis ([beta-hydroxybutyrate] ([BHB]) > 0.5 mM) at follow-up for the MeDi-KD, as compared with only 1 (3%) participant following the MeDi-MCT. MDS-UPDRS Part II and IV scores decreased by a mean of -1.4 (SD: 4.2; p = 0.039) and -1.0 (SD: 3.0; p = 0.044) points, respectively, following the MeDi-MCT.ConclusionsWhile both Mediterranean-ketogenic interventions appear safe in the short-term in PwP, their feasibility is called into question by a high study dropout rate (37%) and modest adherence. Preliminary benefits observed in patient-reported motor experiences were paradoxically limited to the MCT-supplemented MeDi, in which ketosis was not reliably achieved. Together, our findings indicate the need to refine behavioral strategies to optimize dietary awareness and adherence in future trials.Trial RegistrationThe trial was registered on ClinicalTrials.gov: NCT05469997.
Home-Based time-constrained reactive training enhances movement speed in upper and lower limbs in Parkinson's disease: A randomized controlled trial.
Villamil-Cabello E, Molinero-Martín E, Luque-Casado A … +1 more , Fernández-Del-Olmo MA
J Parkinsons Dis · 2026 Mar · PMID 41615860 · Publisher ↗
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...
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.
VR-based quantitative oculomotor analysis and association with regional brain atrophy in MSA.
Fu Y, Wan L, Chen Z … +12 more , Wang C, Chen D, Ouyang R, Wu X, Long X, Du K, Xiao X, He R, Peng L, Qiu R, Tang B, Jiang H
J Parkinsons Dis · 2026 Mar · PMID 41615782 · Publisher ↗
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)...
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], < 0.001); reduced prosaccadic (PS) average velocity (194.80 ± 82.45 °/s vs. 263.07 ± 68.17 °/s, < 0.001); and reduced antisaccade (AS) average velocity (165.82 ± 85.75 °/s vs. 257.05 ± 74.39 °/s, < 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, < 0.001), whereas AS accuracy was positively correlated with MoCA scores (r = 0.375, = 0.001). Voxel-based morphometry revealed significant associations between these oculomotor parameters and atrophy in the cerebellum and frontal gyrus ( < 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.
Faster reaction times of CSF alpha-synuclein seed amplification assay predict the diffuse malignant subtype of Parkinson's disease at 10-year follow-up.
Grillo P, Riboldi GM, Pisani A … +2 more , Kang UJ, Fereshtehnejad SM
J Parkinsons Dis · 2026 Mar · PMID 41610263 · Publisher ↗
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...
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.
Analysis of α-synuclein seed amplification assay in carriers of and pathogenic variants.
Fraser KB, Mirelman A, Mabrouk OS … +15 more , Omer N, Concha-Marambio L, Gurevich T, Bar-Shira A, Gana-Weisz M, Goldstein O, Orr-Urtreger A, Kestenbaum M, Cedarbaum JM, Dam T, Shirvan JC, Giladi N, Graham D, Alcalay RN, Thaler A
J Parkinsons Dis · 2026 Mar · PMID 41574889 · Publisher ↗
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...
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 and 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 -PD (14/14) participants were αS-SAA positive at baseline versus only 5/13 -PD participants (p < 0.001); 44/45 participants with longitudinal follow-up-maintained baseline αS-SAA status at year 2.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 -NMCs (p < 0.001) and NMNCs (p < 0.001).ConclusionsIn 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.
Serum phosphorylated tau 217 in variant carriers with and without Parkinson disease.
Menozzi E, Mezabrovschi R, Nazeer A … +7 more , Anderson A, Loefflad N, Heslegrave AJ, Veleva E, Drotsevitch V, Gegg M, Schapira AH
J Parkinsons Dis · 2026 Mar · PMID 41569009 · Publisher ↗
It is unclear whether Alzheimer disease pathology drives cognitive decline in Parkinson disease (PD) patients carrying variants. We evaluated levels of serum phosphorylated tau 217 (p-tau217) in samples from 29 -PD, 32...
It is unclear whether Alzheimer disease pathology drives cognitive decline in Parkinson disease (PD) patients carrying variants. We evaluated levels of serum phosphorylated tau 217 (p-tau217) in samples from 29 -PD, 32 idiopathic PD, 20 non-manifesting variant carriers (-NMC) and 31 healthy controls. No differences were detected between PD groups. -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 -PD. Whether p-tau217 levels in -NMCs can predict conversion to PD or are a marker of cognitive decline, irrespective of PD, remains unknown.
Dual-Risk axis: mutations and occupational pesticide exposure in Parkinson's disease.
Üstündağ ZH, Özçelik H, Koker I … +9 more , Özkan P, Kar İ, Ozmutlu BE, Mutlu EİG, Yildiz GD, Yekedüz MK, Eminoğlu FT, Akbostancı MC, Yilmaz R
J Parkinsons Dis · 2026 May · PMID 41549707 · Publisher ↗
BackgroundOccupational pesticide (OcP) exposure and pathogenic variants are established risk factors for Parkinson's disease (PD). However, whether they interact to influence disease onset or severity remains uncertain....
BackgroundOccupational pesticide (OcP) exposure and pathogenic 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 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). 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 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 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 variants, supporting a gene-environment "dual-hit" model. However, OcPs did not modify AOO or disease severity once PD was manifest.
The road for developing new pharmacological therapies for Parkinson's disease: Current trends and targets in clinical trials.
Machado T, Duarte GS, Outeiro TF … +1 more , Ferreira JJ
J Parkinsons Dis · 2026 Jul · PMID 41543973 · Publisher ↗
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 featur...
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.
Anxiety is associated with increased risk of suicidality in Parkinson's disease.
Lam JS, Tosefsky KN, Zhu J … +7 more , Meng D, Uzelman P, Pio F, Ainsworth NJ, Vila-Rodriguez F, Howard AK, Appel-Cresswell S
J Parkinsons Dis · 2026 Mar · PMID 41493876 · Publisher ↗
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 investi...
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; = 0.001), higher BDI-II suicidal ideation item score (OR = 32.43; 95% CI: 7.78-135.12; < 0.001), and benzodiazepine use (OR = 13.88; 95% CI: 2.77-69.57; = 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.
Consensus expert recommendations for management of dysphagia during hospital admission in Parkinson's disease.
Safarpour D, Brooks A, Smiley A … +17 more , Katzka DA, Shprecher DR, Greene JG, Pahwa R, Troche MS, Kriegel Z, Peron EP, Bryant A, Fasano A, Ochoa M, Ramirez-Zamora A, Acevedo M, Blackwell GM, Pfeiffer RF, Parkman HP, Quigley EM, Cloud L
J Parkinsons Dis · 2026 Feb · PMID 41490026 · Publisher ↗
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...
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.
An online platform to increase access to gait rehabilitation for underserved Parkinson's disease communities.
Capato TT, Tosserams A, Bloem BR … +1 more , Nonnekes J
J Parkinsons Dis · 2026 Mar · PMID 41468460 · Publisher ↗
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 eva...
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.
Discrepancies between patient and caregiver reports of daily living abilities in Parkinson's disease.
Jin B, Cheon SM
J Parkinsons Dis · 2026 Mar · PMID 41460560 · Publisher ↗
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 rat...
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.
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