Journal Of Parkinson's Disease[JOURNAL]
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200 papers
The road towards faster development of novel pharmacotherapies for persons with Parkinson's disease.
Outeiro TF, Bloem BR, Kalia LV … +1 more , Ferreira JJ
J Parkinsons Dis · 2026 Jul · PMID 42399098 · Publisher ↗
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Mortality rate, main causes of death and factors associated with higher mortality hazard in late stage Parkinson's disease.
Rosqvist K
J Parkinsons Dis · 2026 Jun · PMID 42359890 · Publisher ↗
BackgroundA cohort of 107 patients in late stage Parkinson's disease (PD) was followed for a decade.ObjectiveTo assess mortality rate, main causes of death and factors associated with higher mortality hazard.MethodsLate...
BackgroundA cohort of 107 patients in late stage Parkinson's disease (PD) was followed for a decade.ObjectiveTo assess mortality rate, main causes of death and factors associated with higher mortality hazard.MethodsLate stage PD was defined as Hoehn and Yahr IV-V in "on" or ≤ 50% independency in activities of daily living (ADL). Medical records and mortality records were used to obtain data on mortality.ResultsAfter three years from baseline, 52 (54%) of the participants were alive, after five years 30 (31%) and after seven years 14 (15%). The most common main cause of death was aspiration pneumonia (34%), followed by sepsis (16%), unspecified pneumonia (13%), ileus (5%) and Covid-19 (5%). Baseline variables significantly associated with higher mortality hazard were worse ADL independency ( < 0.001), worse Hoehn and Yahr stage ( < 0.001), worse motor function ( < 0.001), worse cognition ( < 0.001) higher age ( = 0.005), worse perceptual problems/hallucinations ( = 0.020) and having moved to a nursing home ( = 0.021). In a multivariable model, worse motor function ( = 0.001), worse depressive symptoms ( = 0.023) and worse cognition ( = 0.042).ConclusionsThe present end-of-life data provide enhanced knowledge on factors associated with higher mortality hazard in late stage PD. As aspiration pneumonia is the most common cause of death in PD worldwide and swallowing difficulties with the risk of aspiration are common in late stage PD, enhanced focus on prevention and treatment is essential. This may contribute to a better understanding of and care for late stage PD.
Abnormal motor control effort costs in Parkinson's disease patients with apathy.
Schönhals J, Al Ajia M, Meder D … +4 more , Gonzalez-Escamilla G, Schröter N, Groppa S, Herz DM
J Parkinsons Dis · 2026 Jun · PMID 42359824 · Publisher ↗
BackgroundIn Parkinson's disease, abnormalities in reward-effort trade-offs are thought to underlie both apathy and bradykinesia. However, it remains unclear whether effort cost computations contribute to these symptoms...
BackgroundIn Parkinson's disease, abnormalities in reward-effort trade-offs are thought to underlie both apathy and bradykinesia. However, it remains unclear whether effort cost computations contribute to these symptoms independently of reward, and which exact effort costs are involved.ObjectiveTo assess whether effort-based decision-making in the absence of any explicit rewards differs between Parkinson patients and healthy controls and to explore whether putative differences are related to apathy or bradykinesia.MethodsTo address this, we developed a novel decision-making task that isolated physical effort costs from reward processing. Twenty-one Parkinson patients tested on and off dopaminergic medication, and 20 healthy participants, had to choose between two options that differed only in their requirements of force effort, either requiring larger total amounts of force or greater changes in force. We quantified participants' preference for these different effort types and their sensitivity to changes in relative effort.ResultsPatients differed from healthy participants in both overall effort preference ( = 0.009) and sensitivity to changing efforts ( = 0.036), being more likely to choose options requiring overall lower force levels and more influenced by increasing requirements of changes in force. These effects were unaffected by dopaminergic medication. Importantly, sensitivity to increasing requirements for changes in force was associated with apathy ( = 0.004), but not bradykinesia.ConclusionOur findings suggest that, beyond well-known diminished responses to potential rewards, apathy in Parkinson's disease is related to aberrant effort cost computations, in particular those involving dynamic changes in movement, during decision-making.
Deficits in episodic memory and executive functions in relation to CB1 receptor availability in Parkinson's disease.
Ajalin RM, Al-Abdulrasul H, Tuisku JM … +6 more , Karrasch M, Hirvonen J, Kirjavainen AK, Zetterberg H, Rinne JO, Brück AE
J Parkinsons Dis · 2026 Jun · PMID 42351388 · Publisher ↗
BackgroundThe endocannabinoid system (ECS) is important for several neurophysiological functions, including the regulation of emotions and cognitive processes. The most abundant brain cannabinoid receptor is cannabinoid...
BackgroundThe endocannabinoid system (ECS) is important for several neurophysiological functions, including the regulation of emotions and cognitive processes. The most abundant brain cannabinoid receptor is cannabinoid receptor type 1 (CB1R). Several preclinical studies in Parkinson's disease (PD) models suggest that modulating CB1R may impact cognitive processing. However, there are very limited studies of the relation between CB1R and cognitive processing in PD patients.ObjectiveTo explore the relationship between CB1R availability and cognitive dysfunction in PD with [18F]FMPEP-d2 positron emission tomography (PET).MethodsA total of 23 individuals with PD underwent [18F]FMPEP-d2 PET to measure cerebral CB1R availability. Cognitive symptoms were evaluated using a standardized neuropsychological test battery covering various cognitive domains, such as episodic and working memory, executive functioning, language function, visuospatial function and attention, and were correlated with CB1R availability using voxel-wise regression analysis corrected for multiple comparisons using false discovery rate (FDR) at p < 0.01.ResultsPD patients with poorer performance in episodic memory tests showed lower CB1R availability, particularly in the cingulate, temporal, and visual cortices, and thalami. Also, PD patients with poorer executive functioning showed lower CB1R availability predominantly in the insulae, caudate nuclei, thalami, brainstem, and temporal cortices. No relationship was found between CB1R availability and language function, visuospatial function, or working memory capacity.ConclusionsDecreased CB1R availability in PD patients is correlated with episodic memory impairment and executive dysfunction, suggesting that the ECS has a role in the pathophysiology of cognitive symptoms in PD.
Rationale and current status of fecal microbiota transplantations for Parkinson's disease.
Bruggeman A, Vandenbroucke RE, Santens P
J Parkinsons Dis · 2026 Jun · PMID 42343653 · Publisher ↗
Treating a neurological disorder through the gut may seem counterintuitive, yet multiple lines of evidence highlight the gut's important role in Parkinson's disease (PD). Prodromal gastrointestinal symptoms, the presence...
Treating a neurological disorder through the gut may seem counterintuitive, yet multiple lines of evidence highlight the gut's important role in Parkinson's disease (PD). Prodromal gastrointestinal symptoms, the presence of aggregated α-synuclein in enteric neurons, increased intestinal inflammation, and impaired epithelial barrier integrity all point to gut-level involvement in PD pathophysiology. The gut microbiome, markedly altered in individuals with PD, may be a key driver of these changes. Fecal microbiota transplantation (FMT) is currently the most effective strategy for achieving broad and durable modifications of gut microbiota composition. However, FMT is a complex, multi-step procedure requiring stringent methodological control. Modulating gut bacteria has demonstrated therapeutic potential in preclinical models of PD, and recent clinical trials have begun evaluating FMT in patients, although outcomes have been variable. In this review, we examine potential explanations for these divergent results, with a particular focus on methodological differences across trials. We also outline future directions for optimizing FMT study design in PD and discuss how these insights may guide the development of next-generation microbiota-targeted therapies.
Basal ganglia neurophysiological markers of non-motor symptoms in Parkinson's disease: A systematic review.
Keulen BJ, Beudel M, Malekzadeh A … +2 more , de Bie RM, Swinnen BE
J Parkinsons Dis · 2026 Jun · PMID 42334335 · Publisher ↗
BackgroundDeep brain stimulation (DBS) for Parkinson's disease (PD) primarily improves motor symptoms but leaves non-motor symptoms (NMS) largely unattended. Neurophysiological markers associated with specific symptoms c...
BackgroundDeep brain stimulation (DBS) for Parkinson's disease (PD) primarily improves motor symptoms but leaves non-motor symptoms (NMS) largely unattended. Neurophysiological markers associated with specific symptoms could improve DBS programming. We systematically reviewed the evidence linking basal ganglia local field potentials (LFP) to NMS in PD.MethodsThe literature search (Medline, Embase, Scopus, and Web of Science) on August 20, 2024 yielded 1066 records. Studies were included if they focused on patients with idiopathic PD treated with DBS of the subthalamic nucleus (STN) or globus pallidus interna (GPi) and reported on the relationship between LFP data and NMS. The study risk of bias was evaluated using the Prediction Model Risk of Bias Assessment Tool (PROBAST). A narrative synthesis of results was provided.ResultsTwenty-one studies were included, focusing on impulse control disorders (n = 8), sleep-wake disorders (n = 5), depressive symptoms (n = 4), cognitive dysfunction (n = 3), hypomania (n = 1) and lower urinary tract symptoms (n = 1). Seven studies had a high risk of bias. Theta and alpha power in the STN were frequently associated with neuropsychiatric symptoms and cognitive function. Beta power in the STN and GPi was linked to sleep-wake disorders and urinary dysfunction.ConclusionsOverall, evidence on basal ganglia physiomarkers of NMS in PD remains limited. Further research is essential to develop patient-specific stimulation paradigms targeting NMS, which could significantly improve the quality of life of individuals with PD.OtherThis systematic review was registered with the International Prospective Register of Systematic Reviews (CRD42024495284). There was no specific funding for this study.
Agreement between relatives of Parkinson's patients and clinical observer in home diary assessments.
Janz C, Timpka J, Storch A … +2 more , Paul G, Odin P
J Parkinsons Dis · 2026 Jun · PMID 42334331 · Publisher ↗
BackgroundThe Parkinson's Disease (PD) Home Diary (HD) is a common clinical outcome measure, but studies show only fair agreement between clinical observer and patient assessments, with no significant improvement after p...
BackgroundThe Parkinson's Disease (PD) Home Diary (HD) is a common clinical outcome measure, but studies show only fair agreement between clinical observer and patient assessments, with no significant improvement after patient training.ObjectivesTo investigate the agreement between a clinical observer and relatives of PD patients when assessing the patient's motor status in the HD. Agreement was also assessed for relative-patient and patient-observer pairs.MethodsThis observational study included 28 PD patients with motor fluctuations and their relatives. It involved a screening visit with structured training on motor fluctuations and one day of motor ratings, where the observer, relative, and patient independently assessed the patient's motor state in the HD half-hourly.ResultsObserver, patient, and relative triads completed 445 HD assessment sets. Temporal agreement was fair for observer-relatives (Cohen's κ = 0.250) and relatives-patients (κ = 0.230), but slight for patients-observer (κ = 0.120). For observer-relatives, agreement was highest for "On without dyskinesia" (71%), and lowest for "Off" (26%). Daily time distributions differed significantly between relatives and the clinical observer for "Off" ( = 0.006) and "On without dyskinesia" ( = 0.012), but not for "On with dyskinesia" ( = 1.000).ConclusionsThis study reports fair temporal agreement of motor state assessments between relatives-observer and relatives-patients, with slight agreement between patients-observer. Relatives' assessments of daily time in different motor states showed significant differences from the clinical observer assessments. This further highlights the challenges in obtaining reliable motor status data and the need for further research into objective assessment methods.
Mapping the Parkinson's pandemic: Unveiling and addressing the global burden.
Shalash A, Schumacher-Schuh AF, Salama M … +4 more , Noyce A, Ha ULN, Chew Seng Tan L, Tanner CM
J Parkinsons Dis · 2026 Jun · PMID 42334224 · Publisher ↗
Worldwide, the incidence, prevalence, disability, and mortality associated with Parkinson's disease (PD) have increased substantially, placing an immense strain on healthcare systems across countries of all income levels...
Worldwide, the incidence, prevalence, disability, and mortality associated with Parkinson's disease (PD) have increased substantially, placing an immense strain on healthcare systems across countries of all income levels, prompting the use of the term to emphasize the urgent need for coordinated strategies to address its worldwide impact. This narrative review explores the regional differences in the dramatic increase in PD burden, along with its genetic, environmental, and socioeconomic determinants worldwide. Furthermore, it discusses the healthcare access in different regions and proposes strategies to combat this pandemic. The rising burden of PD is largely driven by population aging, increased life expectancy, and potentially by greater exposure to by-products of industrialization-such as pesticides, air pollution and heavy metals- and declining smoking rates, which vary across world regions. Differences in prevalence, demographic, genetic and lifestyle factors, the impact of urbanization and environmental risk factors, as well as inequality and disparities in access to care and healthcare services, have been outlined, mandating the development of tailored and region-specific strategies to mitigate the pandemic and reduce its burden globally and regionally. These strategies include exploring relevant genetic and environmental determinants, promoting research, increasing public awareness, facilitating early diagnosis and optimal management, improving access to healthcare services, supporting caregivers, encouraging the adoption of protective lifestyle factors, ensuring the availability of essential medications and controlling environmental exposures such as toxicants.
Celebrating the legacy of two decades of Parkinson's disease research in South Africa.
Flisher K, Buck AC, Burns J … +7 more , Madula L, Step K, Atkinson K, Acker D, van Coller R, Carr JA, Bardien S
J Parkinsons Dis · 2026 Jun · PMID 42332426 · Publisher ↗
Plain language summaryCelebrating the legacy of two decades of Parkinson's disease research in South AfricaParkinson's disease (PD) has been well-studied in Western Countries, but there are far fewer studies in other par...
Plain language summaryCelebrating the legacy of two decades of Parkinson's disease research in South AfricaParkinson's disease (PD) has been well-studied in Western Countries, but there are far fewer studies in other parts of the world, especially in Africa. This lack of research is partly because there are insufficient neurologists in many African countries, leading to missed or incorrect diagnoses. Stigma around PD and the absence of national disease registries also make research more difficult. To help fill this gap, our team has spent the past 20 years studying PD in South Africa. We have built a collection of almost 2,000 South African participants and report our main findings here. Overall, we found only 20 PD-causing variants in our collection of 689 unrelated PD cases. Interestingly, some of these genetic findings appear to be unique to South Africans, likely due to the unique genetic composition of the country's population. Our functional studies showed how variants in genes, such as and , disrupt the function of mitochondria. Mitochondria are tiny structures in cells that supply the energy required for the cells to function. Cells die when they do not have the necessary energy, potentially explaining why brain cells die in PD. A third part of our research focuses on curcumin, a natural compound found in turmeric known for its antioxidant and anti-inflammatory effects. Using cell models, including cells from individuals with PD, we found that curcumin can protect cells from damage caused by paraquat, a harmful chemical which has been linked to the development of PD. However, this rescue is only seen when curcumin is given before the damage occurs. This suggests that curcumin may help prevent neuronal loss in PD. In summary, our work adds to global knowledge about the genetics, disease processes, and possible treatments for PD. It also shows what a small African laboratory can achieve, despite limited personnel and resources.
Structural biology of alpha-synuclein amyloid filaments: Implications in synucleinopathies.
do Carmo Gonçalves P, Fernández I, Fernández Outón CO
J Parkinsons Dis · 2026 Jun · PMID 42319017 · Publisher ↗
Synucleinopathies are a group of neurodegenerative disorders characterized pathologically by the presence of neuronal and/or oligodendrocyte inclusions composed of aggregated alpha-synuclein (αS). These disorders can be...
Synucleinopathies are a group of neurodegenerative disorders characterized pathologically by the presence of neuronal and/or oligodendrocyte inclusions composed of aggregated alpha-synuclein (αS). These disorders can be divided into two major sub-types: Lewy body disease and multiple system atrophy, which have distinct clinical and pathological profiles. As is seen with other neurodegenerative diseases, recent evidences suggest that the conformation and molecular organization of αS amyloid filaments deposited in brains might dictate the distinct pathological and clinical profiles in synucleinopathies. Resolving the structure of disease-specific αS aggregates becomes, therefore, of clinical interest. Until recently, the specific conformations of these aggregates at molecular resolution have remained elusive. This is now possible due to the advent and development of cryo-electron microscopy (cryo-EM) technology. This review aims to cover the recent advances in the structural biology of αS amyloid filaments implicated in synucleinopathies, raising a number of critical questions that continue to be investigated. What can we learn from these structures? What are the main structural differences between experimental systems and human tissue derived protein aggregates? What factors drive these differences? Do the amplified assemblies represent faithfully the seed structures? How these new findings improve our understanding of the molecular mechanisms behind fibril formation in disease? Can this knowledge be exploited for the design of diagnostic and therapeutical strategies? These aspects and the recent advances in the field will be addressed and discussed in this work.
Deep brain stimulation in alpha-synuclein models of Parkinson's disease: Bridging the translational gap.
Kondrataviciute L, Weber H, Kapadia M … +8 more , Aguirre-Padilla DH, Fauser M, Valiante TA, Hutchison WD, Milosevic L, Storch A, Kalia LV, Kalia SK
J Parkinsons Dis · 2026 Jun · PMID 42299658 · Publisher ↗
Deep brain stimulation (DBS) is an established therapy for advanced medication-resistant Parkinson's disease (PD), yet its ability to alter the course of the disease remains uncertain. Although preclinical research using...
Deep brain stimulation (DBS) is an established therapy for advanced medication-resistant Parkinson's disease (PD), yet its ability to alter the course of the disease remains uncertain. Although preclinical research using toxin-induced PD models demonstrate neuroprotective effects, clinical studies in PD patients undergoing DBS have not substantiated these findings. This disconnect may be attributed to factors such as the initiation of DBS late in disease, stimulation protocols targeting symptoms rather than pathology, and the limited translational relevance of animal models lacking hallmark alpha-synuclein (α-Syn) aggregation. Incorporating α-Syn-based models may bridge this gap by facilitating the discovery of early electrophysiological biomarkers of pathological progression, refining stimulation parameters to enhance α-Syn clearance, and assessing if early DBS intervention can mitigate neurodegeneration. Yet, only a limited number of DBS studies have employed α-Syn models to date. This review examines the translational gap between preclinical neuroprotection claims and clinical outcomes, focusing on how α-Syn-based models could resolve current limitations in DBS research. Prioritizing these models could clarify whether DBS has the potential to extend beyond symptomatic relief and directly engage PD's underlying neurodegenerative mechanisms. Achieving this goal requires systematic investigation of DBS influences on α-Syn accumulation and its electrophysiological correlates in disease-relevant models.
Evaluation of diagnostic concordance between algorithms for Parkinson's disease dementia.
Mana M, Mana J, Stofanikova P … +3 more , Uhrova T, Jech R, Bezdicek O
J Parkinsons Dis · 2026 Jun · PMID 42277619 · Publisher ↗
Significant number of patients with Parkinson's disease (PD) gradually progress to Parkinson's disease dementia (PDD). Recent proposal for updating current diagnostic criteria for PDD recommends alternative screening tes...
Significant number of patients with Parkinson's disease (PD) gradually progress to Parkinson's disease dementia (PDD). Recent proposal for updating current diagnostic criteria for PDD recommends alternative screening tests and broader functional assessments. To evaluate the diagnostic concordance among algorithms for PDD based on Level I (i.e., screening) criteria and to assess their predictive validity for Level II (i.e., neuropsychological battery) diagnosis. A cross-sectional retrospective analysis of 190 patients with PD who underwent a comprehensive neuropsychological assessment. A total of 68 diagnostic algorithms were operationalized using combinations of scores derived from the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). Functional impairment was based either on the Functional Assessment Questionnaire (FAQ) item 9 or the FAQ total score. Diagnostic concordance was evaluated using Cohen's κ. Predictive validity for Level II classification was assessed using projection predictive variable selection. Estimated PDD rates ranged from 2.1% up to 16.8%. Concordance was moderate to high among algorithms using the same functional impairment definition (κ = 0.75, κ = 0.86) but substantially lower when functional impairment definitions differed (κ = 0.43). A parsimonious screening model combining MoCA Five Words and MMSE Sevens adequately approximated Level II classification and yielded a prevalence-adjustable heuristic decision rule. Diagnostic outcomes for PDD are sensitive to the choice of cognitive and functional instruments suggesting that different algorithms may capture partially distinct constructs. Minimal screening using selected items can approximate Level II PDD diagnosis, but this simplification entails a trade-off between sensitivity and specificity.
Gastroparesis in Parkinson's disease: Diagnostic and clinical implications for optimizing pharmacological treatment.
Damiens Q, Mille V, Faure J … +3 more , Toussirot E, Valnet-Rabier MB, Béreau M
J Parkinsons Dis · 2026 Jun · PMID 42268283 · Publisher ↗
Gastroparesis (GP), defined as delayed gastric emptying (GE) without mechanical obstruction, is an underdiagnosed non-motor symptom of Parkinson's disease (PD) that may affect levodopa pharmacokinetics and contribute to...
Gastroparesis (GP), defined as delayed gastric emptying (GE) without mechanical obstruction, is an underdiagnosed non-motor symptom of Parkinson's disease (PD) that may affect levodopa pharmacokinetics and contribute to motor fluctuations. In PD, GP pathophysiology involves Lewy pathology in the enteric nervous system, neurohormonal dysregulation, gut microbiota alterations, and adverse effects of medications, including levodopa. Disruption of the gut-brain axis further exacerbates gastrointestinal dysmotility, leading to malnutrition, reduced quality of life, and increased hospitalization rates. Clinically, GP delays GE, resulting in erratic levodopa absorption and unpredictable ON/OFF responses. Diagnosis is challenging due to symptom overlap with other gastrointestinal disorders and the lack of validated scales specific to GP in PD. Gastric scintigraphy remains the reference method for assessing GE, although its use is limited by methodological variability and interference from ongoing PD treatments.This review critically examines the epidemiology, pathophysiology, and clinical consequences of GP in PD, and highlights its bidirectional relationship with levodopa pharmacokinetics, particularly its contribution to motor fluctuations. We discuss current pharmacological management strategies, with a focus on the efficacy and safety profile of domperidone. Finally, we propose the hypothesis that the future integration of digestive biomarkers and longitudinal clinical data could contribute to a more individualized treatment approach.
Off-State dyspnea induced by diaphragmatic-chest wall asynchrony in Parkinson's disease: A novel observation and review of the literature.
Li WC, Keng LT, Chen KS
J Parkinsons Dis · 2026 Jun · PMID 42262150 · Publisher ↗
Plain language summaryIn the clinical care of patients with Parkinson's disease (PD), dyspnea is a frequent symptom alongside the classic motor symptoms such as bradykinesia and rigidity. However, the underlying mechanis...
Plain language summaryIn the clinical care of patients with Parkinson's disease (PD), dyspnea is a frequent symptom alongside the classic motor symptoms such as bradykinesia and rigidity. However, the underlying mechanisms of dyspnea in Parkinson's disease and how it is affected by dopaminergic medications like levodopa and dopamine agonists, which represent the mainstay treatment of motor symptoms in Parkinson's disease, are not yet fully understood. Various diagnostic tools exist to help clinicians evaluate patients with respiratory issues. In this case study, we report on the utilization of electromyography of the diaphragm, a previously not described diagnostic tool in the field of PD-related dyspnea, to study a patient with Parkinson's disease presenting with recurrent unexplained dyspnea when the dopaminergic medication wears off. We identified an altered sequence of respiratory motion, that is the contraction of diaphragm and excursion of the chest wall, during medication-off in this patient. We propose that the diaphragm-chest wall asynchrony, being a novel finding, likely leads to impaired mechanical output during breathing and contributes to the patient's experience of dyspnea when the medication wears off.
A case of monotherapy with intracerebroventricular anaerobic dopamine allows complete control of Parkinson's disease symptoms.
Moreau C, Marchand F, Bene J … +4 more , Leclercq C, Foutel V, Fisichella M, Devos D
J Parkinsons Dis · 2026 Jun · PMID 42249265 · Publisher ↗
Plain language summaryContinuous intracerebroventricular administration of anaerobic dopamine (A-dopamine) represents a potential new device-aided therapy option for Parkinson's disease in the stage of severe L-dopa-rela...
Plain language summaryContinuous intracerebroventricular administration of anaerobic dopamine (A-dopamine) represents a potential new device-aided therapy option for Parkinson's disease in the stage of severe L-dopa-related complications. A-dopamine is administered via a telemetry-controlled subcutaneous abdominal pump connected to a catheter implanted in the ventricle, near the striatum. We previously demonstrated its value as an add-on therapy in a Phase I/II trial, which showed a 4.4-hour increase in the duration of perfect control without "off" episodes or dyskinesia, and a 6.2-hour increase in the duration of good autonomy, compared to the best oral treatment with a 60% reduction in oral L-dopa. We present here the case of one such patient who benefited from long-term administration of A-dopamine as monotherapy, as the sole treatment. A dose of 240 mg of A-dopamine during the day and 40 mg at night allowed for complete control of motor symptoms without any dyskinesia, painful dystonia, fluctuations, or mental agitation, and without any oral medication. Monotherapy with A-dopamine produced greater benefits than those of adjunctive therapy added to optimized oral treatment. It is interesting to note that A-dopamine and L-dopa had a different clinical effect, since no dyskinesia or psychic excitation was observed with A-dopamine, unlike with L-dopa.
Prevalence and related factors of blood pressure regulation abnormalities in Parkinson's disease: Orthostatic hypotension and supine hypertension.
Jia J, Zeng J, Gong Y … +3 more , Zhou H, Zeng X, Zou J
J Parkinsons Dis · 2026 Jun · PMID 42240302 · Publisher ↗
BackgroundOrthostatic hypotension (OH) and supine hypertension (SH) are common in patients with Parkinson's disease (PD), contributing to disease-related morbidity and mortality. However, initial OH, a transient blood pr...
BackgroundOrthostatic hypotension (OH) and supine hypertension (SH) are common in patients with Parkinson's disease (PD), contributing to disease-related morbidity and mortality. However, initial OH, a transient blood pressure that decreases immediately after standing, is often unrecognized, and the interactions among OH, SH, and anti-hypertensive therapy remain unclear.MethodsThis single-centre retrospective observational study included 183 patients with PD who underwent an active supine-to-stand test with beat-to-beat blood pressure monitoring. Logistic regression was used to identify factors associated with OH and SH, and linear regression was performed to examine the determinants of postural blood pressure decline and changes in cerebral haemodynamics.ResultsOH occurred in 72.1% of patients, including 27.9% with symptomatic OH; SH was present in 21.9%. Female sex ( = 0.013) and anti-hypertensive therapy ( = 0.026) were associated with lower odds of OH. Older age ( = 0.017), arterial hypertension ( = 0.002), and a high Hoehn and Yahr stage ( = 0.006) were associated with higher odds of SH (AUC 0.80). Increased supine systolic and diastolic blood pressure were associated with increased postural decline (β = 0.40, < 0.001; β = 0.31, = 0.001), whereas anti-hypertensive therapy was associated with decreased postural decline. Among patients with complete middle cerebral artery monitoring data, changes in the pulsatility index were correlated with reductions in cerebral blood flow velocity (β = -11.24; = 0.002).ConclusionsThis study comprehensively characterized the prevalence and determinants of OH and SH in patients with PD. SH was associated with greater decreases in postural blood pressure, whereas anti-hypertensive therapy was associated with smaller decreases. Pulsatility index variation may serve as a physiological marker of cerebral haemodynamic adaptation during an orthostatic challenge.
Aligning incentives for open science in biomedical research: Navigating funder and institutional perspectives.
Roskams-Edris D, Riedijk S, Terzikhan N
J Parkinsons Dis · 2026 Jun · PMID 42240244 · Publisher ↗
As science evolves, so must the systems that support it and evaluate it. Inspired by UNESCO's open science definition, this paper explores how funders and institutions can move beyond the traditional metrics to define sc...
As science evolves, so must the systems that support it and evaluate it. Inspired by UNESCO's open science definition, this paper explores how funders and institutions can move beyond the traditional metrics to define scientific impact and to create a more inclusive, transparent and collaborative research ecosystem. We demonstrate through practical examples how the academic landscape is moving towards more openness as the new standard. We conclude with a discussion of challenges in implementing open science practices and recommendations for funders and institutions that will help to create a more unified framework of recognition and reward of scientific work.
Declining verbal fluency after DBS in Parkinson's disease: Mental speed or executive dysfunction?
Pennings VHM, Verwijk E, de Bie RMA … +2 more , Schuurman R, Geurtsen GJ
J Parkinsons Dis · 2026 May · PMID 42217158 · Publisher ↗
BackgroundDespite the frequent decline in verbal fluency after STN-DBS surgery, the cause of decline remains unclear.ObjectiveThis study investigates whether mental speed and executive dysfunctions are underlying mechani...
BackgroundDespite the frequent decline in verbal fluency after STN-DBS surgery, the cause of decline remains unclear.ObjectiveThis study investigates whether mental speed and executive dysfunctions are underlying mechanisms of the phonemic verbal fluency decline after STN-DBS in Parkinson's patients.MethodsNeuropsychological assessments consisting of phonemic verbal fluency, Trail Making Test (TMT), and Stroop test were conducted before and 6 months after STN-DBS in 94 Parkinson's patients in the Galaxy Trial. A Reliable Change Index (RCI) pre- versus postoperative of verbal fluency was calculated, representing the magnitude of change. Content assessment of phonemic verbal fluency resulted in content profiles (clusters and switches).ResultsA statistically significant decline in postoperative phonemic verbal fluency was found, with statistically significant declined switching, while cluster size remained stable. Postoperative, statistically significant increases in time to perform TMT-B and all Stroop subtests was found. However, phonemic verbal fluency decline was correlated to change scores of Stroop I and II only. Comparisons of declined ( = 23) and improved ( = 11) patients, according to RCI's, revealed that decliners had higher preoperative phonemic verbal fluency scores.ConclusionsPostoperative phonemic verbal fluency decline could not be explained by the proposed underlying mechanisms of mental speed and executive dysfunction. However, the significant correlation of phonemic verbal fluency decline to Stroop I and II change scores suggests other possible underlying mechanisms, like slower speech.
Cerebral metabolic trajectories alterations in multiple system atrophy: A longitudinal FDG-PET study.
Zhao Y, Lin H, Li X … +6 more , Shen Q, Wang J, Zuo C, Wang J, Ge J, Liu FT
J Parkinsons Dis · 2026 May · PMID 42206952 · Publisher ↗
Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder with different metabolic patterns in parkinsonian (MSA-P) and cerebellar (MSA-C) subtypes, but their longitudinal changes are not well und...
Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder with different metabolic patterns in parkinsonian (MSA-P) and cerebellar (MSA-C) subtypes, but their longitudinal changes are not well understood. To characterize longitudinal changes of glucose metabolism and network connectivity in MSA using F-FDG-PET for early diagnosis and disease progression tracking, we retrospectively analyzed 29 MSA patients (17 MSA-P, 12 MSA-C) and 28 healthy controls. Regional glucose uptake was assessed as standardized uptake value ratios (SUVR). We examined inter-regional connectivity via correlation analysis and modeled metabolic decline using nonlinear mixed-effects models. Clinical progression was measured using the Unified Multiple System Atrophy Rating Scale (UMSARS). MSA-P displayed progressive hypometabolism in the putamen, cerebellum, and frontal cortex, while MSA-C showed declines primarily in the cerebellum and frontal regions. Longitudinal modeling indicated a faster putaminal decline in MSA-P ( = -0.015 ± 0.006) than in MSA-C ( = 0 ± 0.011), whereas cerebellar metabolism declined over time in both groups with overlapping slopes in MSA-P ( = -0.022 ± 0.006) and MSA-C ( = -0.022 ± 0.011). Regional metabolic reductions correlated with UMSARS progression (putamen in MSA-P: = -0.59, < 0.001; cerebellum in MSA-C: = -0.62, < 0.001). Significant connectivity disruptions were noted in frontal, basal ganglia, and cerebellar-parietal circuits. Longitudinal FDG-PET reveals distinct metabolic decline patterns in MSA subtypes-putamen in MSA-P and cerebellum in MSA-C-linked to clinical severity. These findings may inform clinical practice and trial design, supporting the use of FDG-PET for biological staging, monitoring disease progression, and potentially evaluating treatment responses.
Parkinson's disease drug therapies in the clinical trial pipeline: 2015-2024.
Buff S, Pilcicka A, Pitzer K … +3 more , Fiske B, Stott SR, McFarthing K
J Parkinsons Dis · 2026 May · PMID 42187233 · Publisher ↗
BackgroundThere is an urgent need to find more effective treatments for motor and non-motor symptoms of Parkinson's disease (PD) and to ultimately discover therapies to slow, stop or reverse the condition.ObjectiveTo pro...
BackgroundThere is an urgent need to find more effective treatments for motor and non-motor symptoms of Parkinson's disease (PD) and to ultimately discover therapies to slow, stop or reverse the condition.ObjectiveTo provide an overview of PD drug therapies in Phase 1-3 clinical trials between 2015-2024 in order to highlight research findings and trends, identify opportunities for further research and funding, and provide a common ground for discussion among the patient, research and funding communities.MethodsA dataset of PD drug clinical trials registered on ClinicalTrials.gov between 2015-2024 was analyzed and classified by trial focus (symptomatic therapy or disease-modifying therapy), trial phase, therapeutic category and drug novelty.ResultsThe dataset included 444 trials, of which 42% were in Phase 1, 46% in Phase 2 and 12% in Phase 3. 63% of the trials were evaluating symptomatic therapies (ST) and 37% were testing disease-modifying therapies (DMT). 52% of the trials were exploring novel treatments, a third were testing repurposed compounds and the remainder were evaluating reformulations of existing PD drugs. 281 drug interventions were evaluated across the 444 trials.ConclusionThe pipeline of clinical trials evaluating PD drug therapies between 2015-2024 contained a diverse set of novel, repurposed and reformulated compounds across a variety of biological pathways. While additional symptomatic treatments received regulatory approval, there are still no treatments to modify the course of the disease.
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