Journal Of Parkinson's Disease[JOURNAL]
Sun
200 papers
Impact and management of cognition on speech and swallow function in Parkinson's disease.
Savage-Black M, Sevitz JS, Rogus-Pulia NM
J Parkinsons Dis · 2026 May · PMID 42185736 · Publisher ↗
Parkinson's disease (PD) is a multisystem neurodegenerative disorder involving motor and nonmotor symptoms. Cognitive impairment, dysarthria, and dysphagia are common during disease progression and are associated with re...
Parkinson's disease (PD) is a multisystem neurodegenerative disorder involving motor and nonmotor symptoms. Cognitive impairment, dysarthria, and dysphagia are common during disease progression and are associated with reduced quality of life, loss of functional independence with activities of daily living, and increased morbidity and mortality. While cognitive impairment, dysarthria, and dysphagia are each well-described in PD, the extent to which cognition influences speech and swallowing function in this population requires further study. This narrative review aims to synthesize current evidence on how cognitive impairment intersects with dysarthria and dysphagia in PD. Relevant literature was identified through targeted database searches and citation tracking, emphasizing correlational and dual-task studies on cognition in relation to speech and swallowing outcomes. Although findings vary across tasks, cognitive domains, and disease severity, the literature collectively suggests that speech and swallowing draw on higher-level cortical processes, particularly attention and executive function, and that cognitive decline and increased cognitive load impact speech and swallowing performance in PD. The burden on the cognitive system is often under-recognized in the context of dysarthria and dysphagia management in PD. Further research that deeply explores the needs of individuals with PD and their care partners across the continuum of cognitive decline is necessary to inform person-centered care, as well as treatment approaches that cooperatively target cognition and speech/swallow function. Finally, future research addressing cognition in the early or even prodromal phase of PD may offer opportunities to increase cognitive reserve and mitigate cognitive decline.
Construct optimization for AAV-mediated human α-syn overexpression, and validation across research settings: Development of a shared tool for the research community.
Pardo J, Mudannayake J, Bernal-Conde LD … +11 more , Sandoval IM, Dong RB, Avallone M, Marmion DJ, Gralen A, Waite L, Heuer A, Davidsson M, Polinski NK, Björklund T, Manfredsson FP
J Parkinsons Dis · 2026 May · PMID 42185734 · Publisher ↗
The adeno-associated virus (AAV) alpha-synuclein (α-syn) overexpression model of Parkinson's disease (PD) shares many etiopathological features of the human disease, including the formation of aggregated α-syn, neuroinfl...
The adeno-associated virus (AAV) alpha-synuclein (α-syn) overexpression model of Parkinson's disease (PD) shares many etiopathological features of the human disease, including the formation of aggregated α-syn, neuroinflammation, and nigral neurodegeneration. However, despite the high face validity of this model, it is notoriously variable, yielding inconsistent results with seemingly similar methodologies. In an effort to streamline the utility of this model for the broader research community, we partnered with The Michael J. Fox Foundation for Parkinson's Research (MJFF) to reduce variability and provide a validated tool to be distributed to the research community. Herein, the intent was to assess numerous vector batches in two distinct research groups, sharing tissue and cross-analyzing data to ensure rigor and reproducibility of this model. We assessed several variables, including AAV serotype, genome structure, and promoter construct. Our final selection consisted of a self-complementary AAV genome, carrying the hybrid chicken beta-actin promoter, packaged into AAV5. The resultant construct provides for dose-dependent nigrostriatal degeneration and associated indices such as neuroinflammation and behavioral impairments. Moreover, as reported by others, we observed significant toxicity using a reporter fluorophore as a control; instead, we generated and validated a null vector as the accompanying control. These vectors and plasmid genomes are available for distribution via MJFF.
Baseline predictors of response to a group-based speech and communication intervention in Parkinson's disease: A secondary analysis of a randomized controlled trial.
Steurer H, Schalling E, Franzén E … +2 more , Gustafsson JK, Albrecht F
J Parkinsons Dis · 2026 May · PMID 42183643 · Publisher ↗
BackgroundSpeech and voice symptoms are common in Parkinson's disease, yet predictors of response to behavioral speech interventions are unclear.ObjectivesTo identify predictors of responsiveness to a speech and communic...
BackgroundSpeech and voice symptoms are common in Parkinson's disease, yet predictors of response to behavioral speech interventions are unclear.ObjectivesTo identify predictors of responsiveness to a speech and communication group-intervention (HiCommunication) and contextualize findings against active controls.MethodsThis secondary analysis of a randomized controlled trial included intervention completers. Responders were defined for voice intensity (increase ≥2 decibels) and voice quality (Acoustic Voice Quality Index decrease ≥0.54). Nineteen baseline clinical, motor, cognitive, perceptual, and acoustic variables were entered into Random Forest classifiers. Primary models excluded the baseline value of the target domain; baseline-including variants were sensitivity analyses. Performance was evaluated using Cohen's kappa, precision, recall, and specificity; key predictors were examined using partial dependence.ResultsIn HiCommunication (n = 35), the primary voice intensity model showed moderate agreement (kappa = 0.57; precision = 0.79; recall = 0.90; specificity = 0.64). Higher baseline perceptual ratings of reduced loudness and overall speech deviation, as well as higher Acoustic Voice Quality Index values, were associated with a higher predicted probability of improvement in voice intensity, whereas higher levodopa equivalent daily dose was associated with a lower response probability; postural instability/gait difficulty or tremor-dominant motor phenotypes showed higher response probability than the indeterminate phenotype. Voice quality models were below chance without baseline Acoustic Voice Quality Index but reached kappa 0.38 when included. Active control models showed low performance.ConclusionsClinically accessible baseline measures predicted improvement in voice intensity following HiCommunication with moderate accuracy. Perceptual ratings may support expectation-setting and individualized planning of group-based speech intervention in Parkinson's disease, but findings require replication.ClinicalTrials.gov ID: NCT03213873, doi: 10.1177/1545968321999053.
Early alcohol initiation is associated with higher lifetime Parkinson's disease risk after accounting for exposure latency.
Chang JC, Yen AM, Chen SL … +2 more , Liou HH, Chen TH
J Parkinsons Dis · 2026 May · PMID 42183635 · Publisher ↗
BackgroundObservational evidence linking alcohol consumption to Parkinson's disease (PD) is inconsistent, potentially because conventional analyses do not account for the long latency between alcohol initiation and clini...
BackgroundObservational evidence linking alcohol consumption to Parkinson's disease (PD) is inconsistent, potentially because conventional analyses do not account for the long latency between alcohol initiation and clinical onset or diagnosis.ObjectiveTo test whether latency-aware modeling changes alcohol-PD associations and whether earlier initiation increases lifetime risk.MethodsWe applied a latency-explicit semi-Markov framework in two longitudinal, community-based screening cohorts in Taiwan. The Keelung cohort (Community A; n = 23,475; aged ≥60 years; 2002-2005) was used for model development, and the Changhua cohort (Community B; n = 90,129; aged ≥50 years; 2005-2022) was used for external application. We compared conventional logistic regression with latency-adjusted relative rates, conducted smoking-stratified analyses, and benchmarked age-specific projections against an independent door-to-door PD survey.ResultsIn Community A, conventional regression suggested an inverse association (odds ratio 0.69; 95% confidence interval 0.53-0.91), whereas latency-adjusted modeling indicated higher PD risk among drinkers (relative rate 1.61; 95% confidence interval 1.32-1.95). Excess risk emerged ∼25, ∼35, and ∼45 years after initiation at ages 20, 30, and 40 years, respectively; alcohol-attributable risk by age 90 was 32.1%, 20.7%, and 4.9%. Smoking shortened estimated latency by 5 years. In Community B, PD incidence was higher among drinkers than non-drinkers, with wider separation at older ages (70-74 years: 58.6 vs 46.0 per 100,000).ConclusionAccounting for exposure timing and latency reversed the apparent protective signal and supported a higher modeled lifetime PD risk with alcohol use, particularly earlier initiation. Incorporating latency may strengthen etiologic inference and inform long-horizon prevention strategies.
Abstracts of the 7th World Parkinson Congress.
J Parkinsons Dis · 2026 Jun · PMID 42175618 · Publisher ↗
Abstract loading — click title to view on PubMed.
Tracking the longitudinal progression of Bradykinesia in Parkinson's disease from videos using VisionMD.
Acevedo G, Lange F, Wong JK … +2 more , Vaillancourt DE, Guarin DL
J Parkinsons Dis · 2026 May · PMID 42170718 · Publisher ↗
BackgroundBradykinesia, a hallmark motor symptom of Parkinson's disease, is difficult to quantify accurately using clinical scales due to coarse nature of the scales and their limited sensitivity to change. VisionMD is a...
BackgroundBradykinesia, a hallmark motor symptom of Parkinson's disease, is difficult to quantify accurately using clinical scales due to coarse nature of the scales and their limited sensitivity to change. VisionMD is an open-source platform for video-based quantification of bradykinesia that complements clinical scale evaluations.ObjectivesTo evaluate whether VisionMD video-based digital measures derived from short Finger Tapping videos can detect longitudinal changes in bradykinesia.MethodsWe analyzed Finger Tapping task videos from 36 individuals with Parkinson's disease at two times points, separated by an average of 1.6 years. Motor function was assessed using the Finger Tapping clinical score and video-based digital measures provided by VisionMD which capture movement speed and timing. Longitudinal changes were assessed using ordinal linear models for clinical scores and linear mixed-effects models for digital measures. Correlations between clinical scores and digital measures were also examined.ResultsDigital measures were significantly correlated to Finger Tapping clinical scores. While overall motor function worsened over time, these changes were not reflected by the Finger Tapping score. In contrast, digital measures derived from Finger Tapping videos detected longitudinal declines in movement speed, revealing longitudinal changes in bradykinesia. When stratified by baseline severity, distinct patterns emerged, highlighting heterogeneity in bradykinesia progression in PD.ConclusionVisionMD's video-based digital measures captured subtle, domain-specific progression of bradykinesia not detected by clinical scores. VisionMD provides an objective tool to monitor PD progression and disentangle the multidimensional components of bradykinesia. Future studies should focus on validating these findings in larger cohorts and from home-based recordings.
Planning for prevention of Parkinson's and related synucleinopathies: A trial design forum (conference abstracts).
J Parkinsons Dis · 2026 May · PMID 42163594 · Publisher ↗
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Handgrip strength and relationship with non-motor symptoms in Parkinson's disease.
Urso D, Barone R, Vilella D … +7 more , Gnoni V, Giugno A, Batzu L, Minnella S, Popławska-Domaszewicz K, Chaudhuri KR, Logroscino G
J Parkinsons Dis · 2026 May · PMID 42160361 · Publisher ↗
BackgroundMuscle weakness, particularly reduced handgrip strength (HGS), is a prominent clinical feature in Parkinson's disease (PD). While the relationship between motor symptoms and muscle strength has been extensively...
BackgroundMuscle weakness, particularly reduced handgrip strength (HGS), is a prominent clinical feature in Parkinson's disease (PD). While the relationship between motor symptoms and muscle strength has been extensively studied, the connection between HGS and non-motor symptoms (NMS) remains less explored.ObjectiveThis study investigates the relationship between HGS and NMS in PD patients, hypothesizing that higher burden of NMS is associated with a reduced HGS.MethodsFifty consecutive PD patients were enrolled and underwent comprehensive neurological and neuropsychological evaluations, 3T MRI scans, routine laboratory tests, and I-Ioflupane SPECT imaging. HGS was measured using a DynEx hand dynamometer, and NMS were assessed using the Non-Motor Symptoms Scale (NMSS). Cognitive function was evaluated with a battery of 18 psychometric tests, and quality of life was assessed using the Parkinson's Disease Questionnaire-8 (PDQ-8).ResultsReduced HGS was observed in the majority of PD patients and was significantly correlated with higher NMSS scores, particularly in mood and cognitive domains. Lower HGS was also linked to poorer quality of life. In linear regression models, NMSS remained a significant predictor of HGS even when controlling for age, sex, and Mini-Mental State Examination scores.Conclusions:Our findings suggest that HGS could serve as a valuable biomarker for non-motor symptoms, including depression and cognitive dysfunction, in PD patients. This study underscores the importance of integrating HGS measurements into clinical practice to identify muscle weakness and cognitive impairment, guiding more targeted interventions to improve patient outcomes.
Neurobiology of exercise in Parkinson's disease.
Rodriguez TN, Smeyne RJ, Smeyne M
J Parkinsons Dis · 2026 May · PMID 42159410 · Publisher ↗
Epidemiological, preclinical, and clinical studies increasingly support exercise as a potent neuroprotective and disease-modifying intervention in Parkinson's disease (PD). Preclinical studies, including toxin- and α-syn...
Epidemiological, preclinical, and clinical studies increasingly support exercise as a potent neuroprotective and disease-modifying intervention in Parkinson's disease (PD). Preclinical studies, including toxin- and α-synuclein-based models, using voluntary, forced, and skilled exercise paradigms demonstrate preservation of nigrostriatal dopaminergic neurons, improved motor function, and activation of convergent pathways. Protective processes include upregulation of neurotrophic factors (BDNF, GDNF, VEGF and Irisin), enhanced mitochondrial biogenesis and oxidative resilience, reduced neuroinflammation, improved basal ganglia synaptic plasticity and increased lysosomal functions. Additional emerging mechanisms underlying exercise-induced neuroprotection involve vascular remodeling, pathways regulating cellular oxygen and hypoxia, modulation of the gut microbiome, and epigenetic reprogramming. Importantly, clinical studies mirror these preclinical findings, demonstrating improvements in motor symptoms, balance, fitness, and quality of life, along with functionally positive changes in exercise-responsive biomarkers such as BDNF, irisin, and glutathione. Collectively, these highlight exercise as a robust, multifaceted therapeutic strategy with significant implications for PD prevention and management. This review synthesizes findings from the past 5 years across preclinical models and patient studies to define how exercise reduces PD risk, slows symptom progression, and engages biological pathways relevant to neuroprotection and restoration.Lay abstractExercise, as a consistent lifestyle habit, is beneficial to overall health with cardiovascular and cognitive benefits; and also supports a better quality of life throughout aging. Exercise has been demonstrated to reduce the risk of developing Parkinsons's Disease as well as to delay the symptoms of PD. In this review we will report recent (2020-2025) preclinical and clinical studies that examine the mechanisms underlying exercise's neuroprotective benefit related to PD.
The Global Parkinson's Genetics Program (GP2): Advancing genetic discovery and capacity building worldwide.
Flores-Ocampo V, Zirra A, Tay YW … +5 more , van Midden V, Mata IF, Noyce AJ, Periñan MT, Global Parkinson's Genetics Program (GP2)
J Parkinsons Dis · 2026 Jun · PMID 42159407 · Publisher ↗
The Global Parkinson's Genetics Program (GP2) is an international initiative funded by Aligning Science Across Parkinson's (ASAP), in partnership with the Michael J Fox Foundation for Parkinson's Research (MJFF), to acce...
The Global Parkinson's Genetics Program (GP2) is an international initiative funded by Aligning Science Across Parkinson's (ASAP), in partnership with the Michael J Fox Foundation for Parkinson's Research (MJFF), to accelerate genetic discovery and improve ancestral representation in Parkinson's disease (PD) and related diseases through collaboration, open data sharing, and research capacity building. Since its launch in 2020, GP2 has assembled the largest and most ancestrally diverse PD dataset to date, integrating genotyping, sequencing, and harmonized clinical data from over 240 cohorts worldwide. Through its structured monogenic and complex disease networks, the program spans rare and common variant discovery to advance understanding of PD genetics. Recent GP2-supported studies have identified more than 50 novel genetic risk factors for PD, including a remarkably common risk variant among people of African ancestry, and have confirmed new candidate causal genes such as . Ongoing efforts include whole-genome burden testing, multiple ancestrally-diverse genome-wide association studies (GWAS), polygenic risk modeling, and expansion into atypical Parkinsonism and prodromal cohorts. Beyond discovery, GP2 has invested extensively in research infrastructure and training, supporting more than 270 early-career investigators through workshops, hackathons, and a trainee-to-trainer mentorship framework. These initiatives build local capacity and empower researchers, particularly in underrepresented regions, to lead future genetic studies. GP2 provides an equitable, collaborative model for accelerating the field's understanding of the genetics of PD and related disorders. Continued expansion will enhance population diversity, refine mechanistic insights, better delineate disease onset and progression, and advance progress toward precision medicine across the Parkinsonian spectrum.Plain language summary titleGP2: Genetics and Capacity Building Worldwide.
Subthalamic nucleus deep brain stimulation connectivity related to apathy outcomes in Parkinson's disease.
Abdou E, Pazira K, Sharp S … +3 more , Summers J, Dhima K, Hacker M
J Parkinsons Dis · 2026 May · PMID 42130470 · Publisher ↗
BackgroundSubthalamic nucleus (STN) deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD); however, apathy is a commonly reported side-effect that counteracts quality of life improvements of...
BackgroundSubthalamic nucleus (STN) deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD); however, apathy is a commonly reported side-effect that counteracts quality of life improvements offered by DBS. To date, the structural connectivity of postoperative apathy is largely unknown.ObjectiveThis study aimed to identify streamlines associated with worsening apathy following STN-DBS in PD.MethodsPatients with PD who received bilateral STN-DBS (n = 53) were pseudorandomized into "training" (n = 38) and "holdout" (n = 15) groups. In the training group, a normative structural connectivity analysis was conducted using pre- and postoperative apathy outcomes [Frontal Systems Behavior Scale (FrSBe) apathy subscale]. The resulting model was cross-validated and then tested in the holdout group.ResultsAn asymmetric profile emerged that was associated with worsening apathy. Right hemisphere streamlines were consistent with the dentatorubrothalamic pathway, connecting to the supplementary motor area. In the left hemisphere, the model included streamlines spanning the anteromedial STN to the anterior cingulate and orbitofrontal areas. The validity of the connectivity model was evaluated using cross-validation paradigms (leave-one-patient-out: R = 0.38, = 0.023; 5-fold: R = 0.46, = 0.004; 10-fold: R = 0.33, = 0.048). The model was used to assess its association with apathy changes in the holdout group (R = 0.71, = 0.005).ConclusionResults suggest that worsening of apathy following STN-DBS in PD involves the stimulation of circuits associated with a range of emotional and motivational processes, potentially disrupting auto-activation and emotional-affective processes in some patients.
Dietary supplements for Parkinson's disease: State of the science.
Prasad A, Shuler MS, Flanagan R … +2 more , Dayal V, Lithander FE
J Parkinsons Dis · 2026 May · PMID 42126821 · Publisher ↗
Parkinson's disease (PD) is the fastest growing neurological condition worldwide with its prevalence set to double by 2050. With no cure in sight, management has turned to lifestyle modification, in particular to diet an...
Parkinson's disease (PD) is the fastest growing neurological condition worldwide with its prevalence set to double by 2050. With no cure in sight, management has turned to lifestyle modification, in particular to diet and exercise. The disease-modifying potential of dietary approaches has been of recent interest, particularly given emerging links between diet and reductions in systemic inflammation, oxidative stress, and alterations in the gut microbiome composition, all of which may modulate neurodegeneration. This review summarises the current 'state of the science' of dietary supplements in modifying disease progression through a lens of the pathophysiological hallmarks of PD. Biomarkers and clinical outcomes that serve as proxy measurements for disease modification are examined, whilst looking ahead at which dietary supplements show the most promise and should be the focus of future research.
Parkinson's through a cultural lens: Diversity in disease expression and care.
Morales-Briceno H, Chen KS, Becker P … +7 more , Williams L, Paramanandam V, Toh TS, Ojo O, Sassi SB, Aldaajani Z, Tan AH
J Parkinsons Dis · 2026 May · PMID 42117791 · Publisher ↗
Living and care experiences with Parkinson's disease (PD) vary widely across cultures. Global heterogeneity in PD disease expression is increasingly recognized, shaped by differences in genetic backgrounds, environmental...
Living and care experiences with Parkinson's disease (PD) vary widely across cultures. Global heterogeneity in PD disease expression is increasingly recognized, shaped by differences in genetic backgrounds, environmental exposures, socioeconomic conditions, and access to healthcare resources. Cultural beliefs, levels of health literacy, and stigma play a critical role in shaping how individuals perceive their illness and influence when and how they seek medical care, their trust in healthcare providers, acceptance of diagnosis, and adherence to recommended treatments. Stigma-both internalized and externally imposed-can lead to social withdrawal, delayed help-seeking, and reduced quality of life. Caregiving experiences are likewise deeply influenced by sociocultural norms, including collectivist versus individualist value systems, gendered expectations, and familial structures, all of which affect the distribution of caregiving responsibilities and perceived caregiver burden. These cultural and structural dimensions contribute to marked disparities in diagnosis, treatment, and long-term support for PD across different populations. To address these inequities, clinical care models must be reoriented to incorporate cultural competence training for healthcare providers, locally tailored public education campaigns to combat stigma, and the development of culturally congruent support systems for patients and families. In parallel, future research must prioritize the inclusion of underrepresented populations and sociocultural contexts in epidemiological studies, clinical trials, and implementation science. Advancing culturally responsive, person-centered models of PD care is essential to dismantling structural barriers, reducing disparities, and promoting equitable outcomes for all people living with PD-regardless of geography, ethnicity, or cultural background.
One world, one goal: Advocacy and policy for a unified Parkinson's response.
Fothergill-Misbah N
J Parkinsons Dis · 2026 May · PMID 42096181 · Publisher ↗
Parkinson's disease is one of the fastest growing neurological disorders with regards to disability and death. Though this burden is felt globally, inequities in research, advocacy, prioritization and funding mean that t...
Parkinson's disease is one of the fastest growing neurological disorders with regards to disability and death. Though this burden is felt globally, inequities in research, advocacy, prioritization and funding mean that the needs of people with Parkinson's disease in low- and middle-income countries, and from marginalized communities in high-income countries, remain poorly recognized. Parkinson's disease is increasingly being acknowledged as a global public health issue requiring a public health response. Global advocacy efforts, awareness-raising initiatives, research collaborations, partnerships and investment in Parkinson's disease have therefore accelerated in recent years, with the positioning of people affected by PD as authoritative voices paramount to this drive. Yet despite this progress, inequalities in access to treatments, care and support persist. Responding to the global burden posed by Parkinson's disease requires sustained, multi-sectoral, concerted action, building on an integrated and systems-oriented approach. The generation of momentum for a public health approach to Parkinson's disease must be met with implementation at the country level, alongside sufficient allocation of resources, monitoring and evaluation. The approach offered in this paper builds on the five cross-cutting strategic objectives outlined in the World Health Organization's Intersectoral global action plan on epilepsy and other neurological disorders 2022-2031 (IGAP) implementation toolkit, offering a platform to build a unified global response to Parkinson's disease. Action should therefore center on the integrated themes of (1) prioritization and governance; (2) diagnosis, treatment and care; (3) promotion and prevention; (4) research and information systems; and (5) a tailored Parkinson's disease-specific public health approach.
Practical approaches to inclusive recruitment practices in Parkinson's disease research.
Chahine LM, Louie N, Disbrow E … +36 more , Marbach A, Augenbraun S, Nguyen BT, Johnson-Turbes A, Parry C, Avripas S, Chandra S, Dean M, Foster ER, Hall D, Hinson V, Kilbane C, Norris SA, Rawls A, Jonas C, Shamim EA, Shulman L, Staisch J, Stimming EF, Xie T, Wilcox M, Ameri A, Breaux S, Padmanaban M, von Coelln R, Singleton A, Blauwendraat C, Bandres-Ciga S, Baykal-Caglar E, Kelliher C, Greenwood K, O'Grady A, Solle J, Kopil CM, Kuhl MM, Black and African American Connections to Parkinson's Disease (BLAAC PD) and the Global Parkinson's Genetics Program (GP2)
J Parkinsons Dis · 2026 Jun · PMID 42095464 · Publisher ↗
In Parkinson's disease (PD), inclusive research recruitment practices are essential to ensure that study findings are generalizable to diverse populations. The definition and implementation of inclusive recruitment pract...
In Parkinson's disease (PD), inclusive research recruitment practices are essential to ensure that study findings are generalizable to diverse populations. The definition and implementation of inclusive recruitment practices are guided by the principles of equity, justice, engagement, and sustainability. However, practical implementation guidance is lacking. This paper shares insights from the Black and African American Connections to Parkinson's Disease (BLAAC PD) study, a PD genetics research study being conducted in the United States that enrolls individuals with and without PD. The inclusive recruitment strategy in BLAAC PD centers around four areas: training and working with study personnel toward equitable research practices, partnering with community members, creating culturally resonant study materials, and customizing practices at the local level. We provide practical examples implemented by BLAAC PD to address each of these areas. We share the materials and tools that the study utilizes for site training, recruitment, and community outreach and engagement. These approaches have potential for application in other PD research studies, to achieve greater diversity in PD research.
Frontal subcortical executive dysfunction and minor hallucinations in Parkinson's disease are linked to sensitivity to somatomotor conflicts.
Potheegadoo J, Duong Phan Thanh LF, Bernasconi F … +14 more , Meyer NH, Jenni L, Maradan-Gachet ME, Stucker C, Dhanis H, Catalano Chiuvé S, Bally JF, Castro Jimenez M, Fleury V, Horvath J, Wicki B, Pagonabarraga Mora J, Krack P, Blanke O
J Parkinsons Dis · 2026 May · PMID 42092258 · Publisher ↗
BackgroundMinor hallucinations (MH) affect 30-60% of patients with Parkinson's disease (PD), and are considered precursors to structured visual hallucinations and cognitive decline. While the link between structured visu...
BackgroundMinor hallucinations (MH) affect 30-60% of patients with Parkinson's disease (PD), and are considered precursors to structured visual hallucinations and cognitive decline. While the link between structured visual hallucinations and dementia is well established, the neuropsychological correlates of MH in PD remain unclear; most studies finding no significant cognitive differences between patients with MH and those without any hallucinations.ObjectivesPresence hallucinations (PH) being among the most prevalent MH in PD, we used a robotic procedure delivering somatomotor conflicts inducing PH experimentally to investigate whether sensitivity to such robot-induced PH aids in detecting cognitive differences between patients with MH and without hallucinations.Methods31 PD patients with MH (PD-MH) and 37 without hallucinations (PD-nH) underwent neuropsychological assessment and the robotic procedure inducing PH. The sensitivity to report robot-induced PH was analyzed in relation to cognitive performance in neuropsychological tests.ResultsPD-MH patients reported more robot-induced PH than PD-nH patients, supporting previous findings. While both groups showed comparable performance in neuropsychological testing, we found a significant association between increased sensitivity to the PH-induction and poorer performance in frontal subcortical cognitive functions, in PD-MH patients, but not in PD-nH patients.ConclusionsThese findings demonstrate that sensitivity to robot-induced PH reveals a previously undetected link between MH and frontal subcortical cognitive deficits in PD, pointing to shared underlying mechanisms between executive dysfunction and somatomotor processes involved in MH. This approach offers a novel and clinically valuable means of identifying early cognitive vulnerability that assessments relying only on standard testing may overlook.
Clinical GDNF delivery methods for Parkinson's disease.
Luz M, Fiandaca MS, Bankiewicz KS
J Parkinsons Dis · 2026 Jun · PMID 42091584 · Publisher ↗
Intracerebral delivery of glial cell line-derived neurotrophic factor (GDNF) therapeutics continues to show promise, especially in Parkinson's disease (PD). However, randomized, placebo-controlled clinical trials using G...
Intracerebral delivery of glial cell line-derived neurotrophic factor (GDNF) therapeutics continues to show promise, especially in Parkinson's disease (PD). However, randomized, placebo-controlled clinical trials using GDNF protein have been inconclusive to date. A major sham-surgery controlled trial using GDNF gene therapy commenced in 2024. In this review we aim to update the reader on the evolution and current state of the art of intracerebral delivery methods for GDNF protein and gene therapy in PD clinical trials. Our intent is to increase the awareness for the importance, subtleties, and pitfalls of intracerebral delivery when reviewing current available results for these therapies and their prospects going forward. We will compare and contrast GDNF protein infusion versus gene therapy strategies and define specific anatomical and physiological details in trial participants that continue to challenge clinicians and investigators attempting to maximize therapeutic coverage of the target putamen. Despite a growing consensus that convection-enhanced delivery (CED) is the optimal intracerebral infusion strategy for localized administration of therapeutics in general and gene therapy products in particular, there is less agreement on the need for related methods, such as the co-infusion of a gadolinium contrast agent and use of intraoperative magnetic resonance imaging (iMRI) to visualize the therapeutic distribution for optimizing target coverage. Whereas certain debates will continue, most investigators and clinicians respond positively to well-designed trials providing clean, conclusive results. Information included in this review is intended to provide additional insights to interested readers, allowing better assessment of details associated with upcoming GDNF therapeutic investigations.Plain language summary titleClinical Delivery Methods for Treatments Based on Glial Cell Line-Derived Neurotrophic Factor (GDNF) in Parkinson's Disease.
Advances in sex-specific single-cell transcriptomic profiling in Parkinson's disease.
Hoof V, Schulze-Hentrich J
J Parkinsons Dis · 2026 May · PMID 42084601 · Publisher ↗
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons and the accumulation of misfolded alpha-synuclein. While traditional bulk RNA-sequencing has provided...
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons and the accumulation of misfolded alpha-synuclein. While traditional bulk RNA-sequencing has provided valuable insights into PD pathology, it fails to capture the complex cellular heterogeneity of the human brain. Advances in single-cell transcriptomics have revolutionized our ability to dissect this complexity, enabling the identification of rare, disease-associated cell populations, or the inference of dysregulated intercellular communication networks. In this review, we discuss methodological and analytical frameworks of single-cell RNA-sequencing and summarize key findings from recent studies using single-cell RNA-sequencing that advance our understanding of PD. We highlight how single-cell transcriptomics has refined our understanding of neuronal vulnerability and revealed critical contributions of non-neuronal cells, particularly microglia and oligodendrocytes, to disease pathology in both human postmortem tissue and experimental model systems. Finally, we discuss emerging evidence for sex-specific molecular alterations in PD and emphasize the importance of sex-aware study design and analysis in future single-cell PD research.
The taste of Parkinson's: How food choices reflect nutritional health.
Phokaewvarangkul O, Sukmueng N, Kuwattanasuchati P … +3 more , Sanyawut K, Rattanapitak N, Bhidayasiri R
J Parkinsons Dis · 2026 Jun · PMID 42059527 · Publisher ↗
IntroductionUnderweight is common in Parkinson's disease (PD), particularly in advanced stages, and is linked to malnutrition and poorer outcomes. Understanding dietary habits and nutritional status may help identify vul...
IntroductionUnderweight is common in Parkinson's disease (PD), particularly in advanced stages, and is linked to malnutrition and poorer outcomes. Understanding dietary habits and nutritional status may help identify vulnerable patients.ObjectiveTo examine dietary habits and their associations with clinical characteristics in underweight versus normal-to-overweight individuals with PD.MethodsThis cross-sectional study included 70 patients with PD attending a tertiary movement disorders centre. Demographic and clinical data were obtained through interviews and medical records. Disease severity was assessed using the Hoehn & Yahr scale and the Unified Parkinson's Disease Rating Scale (UPDRS Part III and IV). Nutritional status was screened using the Mini Nutritional Assessment-Short Form (MNA-SF). Dietary habits were evaluated using a culturally adapted Thai PD dietary questionnaire, and a dietitian estimated daily caloric and fluid intake. Participants were categorized by body mass index as underweight (<18.5) or normal-to-overweight (≥18.5). Group comparisons and logistic regression analyses were performed.ResultsUnderweight patients more often consumed soft or liquid diets and had a higher prevalence of dysphagia. They reported less varied diets with lower meat and vegetable intake, although caloric and fluid intake were similar between groups. Underweight participants had lower MNA-SF scores ( < 0.001) and greater motor complications, including higher UPDRS Part IV scores ( = 0.015). Female gender (OR 18.51), dysphagia (OR 5.97), and dyskinesia (OR 2.03) were independently associated with underweight status.ConclusionUnderweight in PD is associated with female gender, dysphagia, and dyskinesia. Early nutritional screening and management of dysphagia and motor complications may improve outcomes.
Differential effects of levodopa on social cognition in people with Parkinson's disease.
Danaila T, Métereau É, Klinger H … +7 more , Jaulent A, Porte O, Tremblay L, Jaulent P, Laurencin C, Prange S, Thobois S
J Parkinsons Dis · 2026 Apr · PMID 42053208 · Publisher ↗
Social cognition impairment is a frequent non-motor feature of Parkinson's disease. While dopaminergic therapy modulates motor symptoms, its effects on social cognition remain incompletely understood. We investigated the...
Social cognition impairment is a frequent non-motor feature of Parkinson's disease. While dopaminergic therapy modulates motor symptoms, its effects on social cognition remain incompletely understood. We investigated the effects of acute levodopa administration on cognitive and affective Theory of Mind, as well as on emotional resonance to dynamic whole-body social interactions, in 36 people with Parkinson's disease with motor fluctuations and 14 matched healthy controls. Social cognition was assessed using the Mini-Social Cognition and Emotional Assessment (Mini-SEA) and a point-light display task indexing emotional resonance through emotional valence ratings. Patients were evaluated in OFF and ON states during an acute dopaminergic challenge performed according to the CAPSIT-PD protocol, with responsiveness defined as an improvement greater than 50% on the MDS-UPDRS part III. Compared with healthy controls, patients showed impaired cognitive Theory of Mind performance, particularly on the faux pas subtest (p = 0.0001), while affective Theory of Mind based on facial emotion recognition was preserved. Acute levodopa did not improve cognitive or affective Theory of Mind (faux pas OFF vs ON, p = 0.7049). In contrast, emotional resonance was impaired in the OFF state and selectively improved in the ON state, with increased ratings of positive (p = 0.0035) and negative (p = 0.0387) emotional valence. These findings demonstrate a dissociation between Theory of Mind and emotional resonance in Parkinson's disease and show that acute levodopa selectively modulates emotional resonance without restoring Theory of Mind abilities.
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