Journal Of Parkinson's Disease[JOURNAL]
Sun
200 papers
Associations between neuropsychological profile and regional brain FDG uptake in progressive supranuclear palsy.
Doll-Lee J, Klietz M, Greten S … +14 more , Kopp B, Berding G, Brendel M, Wilkens I, Katzdobler S, Levin J, Danek A, Rogozinski S, Höglinger G, Pötter-Nerger M, Buhmann C, Buchert R, Wegner F, Alzheimer’s Disease Neuroimaging Initiative
J Parkinsons Dis · 2025 Jun · PMID 40415458 · Publisher ↗
BackgroundProgressive supranuclear palsy (PSP) is a rare neurodegenerative movement disorder clinically characterized by falls, axial rigidity, vertical supranuclear gaze palsy, bradykinesia, and cognitive decline. There...
BackgroundProgressive supranuclear palsy (PSP) is a rare neurodegenerative movement disorder clinically characterized by falls, axial rigidity, vertical supranuclear gaze palsy, bradykinesia, and cognitive decline. There is a relative lack of studies on the functional neuroimaging correlates of cognitive impairment in PSP.ObjectiveThis study investigated the relationship between regional cerebral glucose metabolism as assessed by static F-fluorodeoxyglucose positron emission tomography (FDG-PET) with global scaling and the profile of cognitive performance according to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test battery in a sample of PSP patients representative of clinical practice.Methods22 PSP patients from three tertiary movement disorder centers with CERAD testing and FDG-PET in close proximity were included retrospectively. Neuropsychological test performance was assessed for correlation with FDG uptake on a voxel-by-voxel basis with cluster-level correction for multiple testing, separately for each subtest.ResultsIn comparison to matched healthy controls, PSP patients showed reduced FDG uptake in the left inferior frontal gyrus and right angular gyrus. Reduced overall cognitive performance according to Montreal Cognitive Assessment was associated with reduced FDG uptake in the right frontal eye field. Word list learning correlated with FDG uptake in the left frontal eye field, while language fluency was linked to FDG uptake in the bilateral premotor and supplementary motor areas.ConclusionsReduction of FDG uptake in PSP primarily affects frontal brain regions and is linked to the performance in specific cognitive domains. These findings may have implications for the interpretation of FDG-PET to support the etiological diagnosis of PSP.
Association of αS-SAA kinetics with clinical scores in the clinical spectrum of Parkinson's disease.
Bellomo G, Paolini Paoletti F, Gaetani L … +5 more , Toja A, Ma Y, Farris CM, Concha-Marambio L, Parnetti L
J Parkinsons Dis · 2025 Jun · PMID 40405674 · Publisher ↗
BackgroundCerebrospinal fluid (CSF) α-synuclein seed amplification assay (αS-SAA) is a recognized biomarker of synucleinopathy. In Parkinson's disease (PD), its potential for predicting clinical outcome needs to be furth...
BackgroundCerebrospinal fluid (CSF) α-synuclein seed amplification assay (αS-SAA) is a recognized biomarker of synucleinopathy. In Parkinson's disease (PD), its potential for predicting clinical outcome needs to be further assessed.ObjectiveTo evaluate the associations between clinical outcome and αS-SAA kinetic parameters in a retrospective cohort of PD patients, also investigating whether CSF total protein content influences such associations.MethodsStudy cohort included cognitively unimpaired PD (PD-CN, n = 40), PD with mild cognitive impairment (PD-MCI, n = 44), and PD with dementia (PDD, n = 10) with available clinical assessment at baseline. Among them, n = 28 PD-CN and n = 31 PD-MCI patients had 2-year follow-up, and CSF biomarkers reflecting pathophysiological pathways other than synucleinopathy.ResultsIn PD-MCI, αS-SAA time-to-threshold (TTT) is associated with longitudinal changes in Mini-Mental State Examination. The association is stronger when accounting for CSF total protein concentration.ConclusionsαS-SAA TTT may represent a prognostic factor for cognitive decline in PD-MCI.
Mortality and causes of death in patients with Parkinson's disease in Taiwan.
Chiou SJ, Hu YH, Chen YC … +3 more , Wang DL, Elbaz A, Lee PC
J Parkinsons Dis · 2025 Jun · PMID 40405653 · Publisher ↗
BackgroundPrevious studies that examined Parkinson's disease (PD) mortality were mostly conducted in Western countries.ObjectsWe compared mortality rates and causes of death in PD patients and persons without PD from Tai...
BackgroundPrevious studies that examined Parkinson's disease (PD) mortality were mostly conducted in Western countries.ObjectsWe compared mortality rates and causes of death in PD patients and persons without PD from Taiwan over 15 years of follow-up.MethodsWithin the National Health Insurance database, we followed 50,290 incident PD patients (2003-2016) and 201,153 matched non-PD participants (controls) until 31/12/2018. We used multivariable Cox proportional-hazards regression models to compare mortality rates and causes of death in PD patients and controls. Due to non-proportionality, we performed stratification by follow-up duration (≤5/>5 years). We examined interactions between PD status participants' characteristics for all-cause mortality.ResultsPD patients had higher all-cause mortality than controls (HR = 1.40, 95% CI = 1.37-1.42); the association was stronger ( < 0.0001) after the first 5 years of follow-up (HR = 1.49 [1.46-1.53]) than before (HR = 1.34 [1.31-1.37]). The strongest associations were observed for suicide (HR = 1.79 [1.52-2.10]), dementia (HR = 1.69 [1.47-1.93]), and pneumonia (HR = 1.57 [1.49-1.65]). The association between PD and death decreased as age increased, and was stronger in patients without comorbidities, depression, and dementia than in those with.ConclusionsTaiwanese PD patients have reduced life expectancy throughout the course of disease with a stronger association after the first 5 years of follow-up. PD had a stronger impact on mortality in younger persons and in those without comorbidities. Prevention of pneumonia and suicide, and appropriate management of dementia and comorbidities would help reduce PD-related mortality. Our findings may help health authorities allocate resources to improve the management of PD patients in order to address PD-related mortality.
Incidence of antiepileptic drug use in Parkinson's disease.
Tuominen S, Tiihonen M, Paakinaho A … +4 more , Koponen M, Kaasinen V, Hartikainen S, Tolppanen AM
J Parkinsons Dis · 2025 Jun · PMID 40405650 · Publisher ↗
BackgroundAntiepileptics are used to treat epilepsy but also, e.g., neuropathic pain, essential tremor and dystonia. It is not known whether they are more commonly used in persons with Parkinson's disease (PD).ObjectiveT...
BackgroundAntiepileptics are used to treat epilepsy but also, e.g., neuropathic pain, essential tremor and dystonia. It is not known whether they are more commonly used in persons with Parkinson's disease (PD).ObjectiveTo assess the incidence of antiepileptic use in a nationwide cohort of persons with PD before and after the diagnosis and compared the findings to a matched cohort without PD.MethodsThis register-based Finnish nationwide cohort included 18365 persons diagnosed with PD between 2001-2015. Incidence of antiepileptic initiations, from 10 years before until 10 years after the PD diagnosis, was compared to an age-, sex-, and region-matched cohort without PD.ResultsAntiepileptics were more commonly initiated for persons with PD (29.3% of PD cohort and 15.2% of comparison cohort). Gabapentinoids were the most commonly initiated antiepileptics in both cohorts. A similar pattern in initiation rates was observed for both gabapentinoids and other antiepileptics, with increased incidence in the PD cohort approximately three years before the diagnosis and a significant peak around the time of PD diagnosis (the initiation rate at the time of PD diagnosis 3/100 and 1/100 person-years, for the PD and comparison cohorts, respectively). Clonazepam initiations were more common in the PD cohort (26.7% of initiations vs. 5.8% in the comparison cohort).ConclusionsThe increase in antiepileptic initiation rates before the diagnosis of PD suggests that they might be used for prodromal motor or non-motor symptoms.
Mild cognitive impairment is not predictive of dementia up to 15 years after subthalamic deep brain stimulation in Parkinson's disease.
Fjeldhøj S, Thomsen BLC, Pedersen PM … +6 more , Jensen SR, Clausen A, Karlsborg M, Jespersen B, Bergdal OK, Løkkegaard A
J Parkinsons Dis · 2025 Jun · PMID 40390641 · Publisher ↗
BackgroundCognitive impairment and dementia are common findings in patients with Parkinson's disease (PD). However, the long-term effects of subthalamic deep brain stimulation (STN-DBS) on cognition remain unclear.Object...
BackgroundCognitive impairment and dementia are common findings in patients with Parkinson's disease (PD). However, the long-term effects of subthalamic deep brain stimulation (STN-DBS) on cognition remain unclear.ObjectiveWe report short- and long-term effects of STN-DBS on cognition in PD.MethodsWe analyzed neuropsychological data before STN-DBS surgery, 3-month post-surgery, 1-year post-surgery and in a long-term follow-up (8-15 years post-surgery) to examine the effects of STN-DBS on cognition.Results81 patients with a mean disease duration of 13.0 years were examined before surgery. 50.6% were identified with mild cognitive impairment (MCI), having a mean disease duration of 14.2 years. Pre-surgical PD-MCI was not associated with clinically diagnosed dementia (PD-D) before death or before long-term follow-up (OR 0.8, 95% CI 0.3-2.2, p = 0.714), but disease duration at the time of surgery was associated with development of PD-D (OR 1.2, 95% CI 1.1-1.3, p = 0.005). Verbal fluency declined significantly 3 months after surgery, while other domains remained unaffected. In neuropsychological testing at long-term follow-up (N = 29), global cognitive impairment or dementia was found in 19 patients. The presence of depressive symptoms before surgery was associated to PD-D at long-term follow-up. Death before long-term follow-up was more common in patients with pre-surgical MCI than in patients with normal cognition.ConclusionsInfluence on cognition was described in a short- and long-term follow-up study up to 15 years after STN-DBS surgery in PD. Disease duration, but not pre-surgical MCI was associated with development of dementia. Impaired verbal fluency was observed both in a short- and long-term follow-up.
Anxiety-related attentional characteristics and their relation to freezing of gait in people with Parkinson's: Cross-validation of the Adapted Gait Specific Attentional Profile (G-SAP).
Rosenblum U, Cocks AJ, Norris M … +2 more , Kal E, Young WR
J Parkinsons Dis · 2025 Jun · PMID 40390627 · Publisher ↗
BackgroundAnxiety often exacerbates freezing of gait (FOG) in people with Parkinson's (PwP). Anxiety-related attentional processes and associated processing inefficiencies, like conscious movement processing (CMP) and ru...
BackgroundAnxiety often exacerbates freezing of gait (FOG) in people with Parkinson's (PwP). Anxiety-related attentional processes and associated processing inefficiencies, like conscious movement processing (CMP) and ruminations, can substantially impact movement control. However, their impact on FOG remains largely unexplored.ObjectiveTo validate an adapted 10-item (1-5 Likert scale) Gait-Specific Attentional Profile (G-SAP) in PwP and assess if adapted G-SAP-subscales (Physiological Arousal, CMP, Rumination, and Processing Inefficiencies) are associated with self-reported FOG frequency.MethodsWe recruited 440 PwP (M = 65.5 ± 8.7; 5.8 ± 5.0 years since diagnosis) across the UK. Participants completed the adapted G-SAP and questionnaires on demographics, medical background, and FOG frequency. We assessed adapted G-SAP's internal consistency, structural validity, and subscale scores associations with FOG frequency.ResultsThe adapted G-SAP showed acceptable internal consistency (α≥0.66) and acceptable/good model fit (comparative fit index = 0.976). Physiological Arousal and CMP subscale scores presented weaker correlations for PwP with FOG (PwP + FOG, r = 0.52) compared to PwP without FOG (PwP-FOG, r = 0.77; p = 0.006). Higher Rumination (OR: 1.323, 95%CI: [1.214-1.440]) and Physiological Arousal (OR: 1.195, 95%CI:[1.037-1.377]) were significantly associated with higher FOG frequency, controlling for age, time since diagnosis and balance/gait problems.ConclusionsThe adapted G-SAP is reliable and convenient to measure and identify potentially maladaptive anxiety-related attentional processes that may impact FOG. Results suggest that PwP who experience more worrisome thoughts and greater physiological arousal in daily life are likelier to freeze. Compared to PwP-FOG, for PwP + FOG high physiological arousal was associated with reduced goal-directed focus of attention. Future research will determine if this is a causal risk factor.
Sex-specific progression of Parkinson's disease: A longitudinal mixed-models analysis.
Hanff AM, McCrum C, Rauschenberger A … +8 more , Aguayo GA, Pauly C, Jónsdóttir SR, Tsurkalenko O, Zeegers MP, Leist AK, Krüger R, NCER-PD consortium
J Parkinsons Dis · 2025 Jun · PMID 40388933 · Publisher ↗
BackgroundDespite its relevance, the clinical progression of motor- and non-motor symptoms associated with Parkinson's disease (PD) is poorly described and understood, particularly in relation to sex-specific differences...
BackgroundDespite its relevance, the clinical progression of motor- and non-motor symptoms associated with Parkinson's disease (PD) is poorly described and understood, particularly in relation to sex-specific differences in clinical progression.ObjectiveIdentification of differential aspects in disease progression in men and women with PD.MethodsLinear mixed-model analyses of 802 people with typical PD from the Luxembourg Parkinson's study's prospective cohort (median time of follow-up = three years). We estimated the effect of time and its moderation by sex (alpha ≤ 0.05), including confidence intervals, for the following outcomes: MDS-UPDRS I-IV, Starkstein Apathy Scale, Beck Depression Inventory, Montreal Cognitive Assessment (MoCA), Sniffin' sticks, bodily discomfort, rapid eye movement sleep behavior disorder questionnaire, PD Sleep Scale (PDSS), Munich Dysphagia Test-PD, Functional Mobility Composite Score, and the MDS-based tremor and postural instability and gait disturbances scale. In addition, the marginal means illustrated the symptoms' trajectories in men and women. Men and women had similar age.ResultsOverall, we observed a slower progression (interaction effect) in women compared to men, especially for MoCA (-0.159, 95%CI [-0.272, -0.046], p = 0.006), PDSS (-0.716, 95%CI [-1.229, -0.203], p = 0.006), PIGD (0.133, 95%CI [0.025 0.241], p = 0.016), and MDS-UPDRS II (0.346, 95%CI [0.120, 0.572], p = 0.003). The finding for MDS-UPDRS II was significant (FWER of 5%) after adjustment for multiple comparisons (Bonferroni-Holm).ConclusionsNext to the further exploration of sex-specific progression, interventions, proactive monitoring and communication strategies tailored to the symptoms progression and needs of men and women need to be developed.
Decline of olfactory function in Parkinson's disease: A ten-year longitudinal study.
Roos DS, Klein M, Doty RL … +1 more , Berendse HW
J Parkinsons Dis · 2024 Oct · PMID 40383932 · Publisher ↗
BackgroundOlfactory dysfunction is a prodromal sign of Parkinson's disease (PD) present in up to 90% of patients. However, it is unclear whether or not olfactory function worsens over the course of the disease.ObjectiveI...
BackgroundOlfactory dysfunction is a prodromal sign of Parkinson's disease (PD) present in up to 90% of patients. However, it is unclear whether or not olfactory function worsens over the course of the disease.ObjectiveIn this study we examined whether the rate of decline of olfactory function in PD patients exceeds the expected age-related decline.MethodsOlfactory function was tested in 90 PD patients at baseline (age at baseline 58.3 years, 68.9% males) and an average 10 years later using the 40-item University of Pennsylvania Smell Identification Test (UPSIT). To screen for concomitant cognitive deficits as a potential confounder, the Mini-Mental State Examination (MMSE) was used.ResultsAt baseline, the mean UPSIT score was 22 points. Over the average 10-year follow-up period olfactory function decreased in 81.1% of PD patients, even in the youngest patients in whom no age-related decline was expected. The mean decrease was six UPSIT points (< 0.001), which exceeds the expected age-related decline derived from a previous study. When excluding patients with an MMSE score below 24, reflecting cognitive deficits that might interfere with olfactory test performance, UPSIT score still decreased by almost 7 points over the follow-up period.ConclusionsOlfactory function in PD declines more rapidly with increasing disease duration than can be explained by aging or cognitive decline alone. As such, olfactory function appears to be a clinical marker of disease progression in PD that can be measured non-invasively and deserves consideration as part of multimodal phenotyping to monitor disease progression.
Effects of theta burst stimulation on the Parkinsonian gait disorder and cortical gait-network activity.
Dutke J, Gehlenborg J, Heise M … +8 more , Hamel W, Gerloff C, Thomalla G, Magnus T, Engel AK, Moll CK, Gulberti A, Pötter-Nerger M
J Parkinsons Dis · 2025 Jun · PMID 40383539 · Publisher ↗
BackgroundThe Parkinsonian gait disorder and freezing of gait (FoG) are challenging symptoms of Parkinson's disease (PD).ObjectiveTo assess the effect of subthalamic theta burst deep brain stimulation (TBS-DBS) on the Pa...
BackgroundThe Parkinsonian gait disorder and freezing of gait (FoG) are challenging symptoms of Parkinson's disease (PD).ObjectiveTo assess the effect of subthalamic theta burst deep brain stimulation (TBS-DBS) on the Parkinsonian gait performance in real-world conditions and cortical activity indexed by mobile EEG.MethodsIn this monocentric, randomised, double-blind, short-term study, 12 age-matched controls (11 male, age 59 ± 8 years) and 15 PD participants (14 male, age 62 ± 9 years, disease duration 15 ± 6 years) with subthalamic stimulation (76 ± 39 months) were assessed with clinical scores (FoG-Course, MDS-UPDRS) and a standardized gait course simulating everyday life situations. Three DBS algorithms were applied in a randomized order with intertrial waiting periods of 30 min: (1) OFF-DBS; (2) cDBS; (3) TBS-DBS (interburst frequency 5 Hz, intraburst frequency 200 Hz) with regular medication. During the standardized gait course a mobile, 24-channel EEG system and 6 wearable axial kinematic sensors were used.ResultsThe primary outcome, the relative change of FoG-Course by DBS, was not superior with TBS-DBS compared to cDBS in the entire sample. Seven of fifteen PD participants rated subjectively TBS-DBS equal or better than cDBS ("TBS-preference group"). EEG recordings revealed movement-induced alpha and beta suppression in premotor and motor cortex in both cDBS and TBS-DBS conditions in PD with slightly different patterns between the DBS modes.ConclusionsIn this pilot trial, TBS-DBS showed benefits in the subjective perception of gait in a subgroup of PD patients accompanied by specific cortical network changes. TBS-DBS merits further investigation in future larger cohort studies with longer observation periods.
Intestinal biomarkers, microbiota composition, and genetic predisposition to inflammatory bowel disease as predictors of Parkinson's disease manifestation.
Chai Z, Ouyang Y, Debebe A … +12 more , Picker M, Lee WJ, Fenton S, Becker-Dorison A, Augustin-Emmerichs K, Schwiertz A, Weber SN, Lammert F, Hu J, Fang G, Unger MM, Peter I
J Parkinsons Dis · 2025 Jun · PMID 40336252 · Publisher ↗
BackgroundParkinson's disease (PD) is often accompanied by gastrointestinal symptoms. While elevated inflammatory biomarkers have been reported in PD patients compared to controls, the role of intestinal dysmotility and...
BackgroundParkinson's disease (PD) is often accompanied by gastrointestinal symptoms. While elevated inflammatory biomarkers have been reported in PD patients compared to controls, the role of intestinal dysmotility and inflammation in disease manifestation is not fully understood.ObjectiveThis study sought to determine if fecal biomarkers and genetic predisposition to intestinal inflammation could help identify PD subtypes for future targeted therapies.MethodsThe association of disease activity, assessed through United Parkinson's disease Rating Scale (UPDRS) and Non-Motor Symptoms Questionnaire (NMSQ), with constipation severity, fecal calprotectin and six short-chain fatty acid (SCFA) levels, polygenic risk scores (PRS) for inflammatory bowel disease (IBD) and PD, and microbiota diversity were investigated in 95 participants with established PD using regression analyses. Unsupervised k-means clustering was applied to stratify PD patients based on inflammatory biomarkers.ResultsHaving constipation was linked to worse mentation (UPDRSI, adj. = 0.03) and more limited daily living activities (UPDRSII, adj. = 0.03), with symptom severity linearly associated with higher disease activity (UPDRSI, adj. = 0.002; NMSQ-total, adj. = 0.02). Fecal calprotectin was elevated in those with constipation ( = 0.02) and associated with longer disease duration irrespective of the age (adj. = 0.02). Cluster analysis demonstrated that PD patients with a higher non-motor symptom UPDRSII score were more likely to have more severe constipation, lower fecal SCFA levels, lower bacterial diversity, and higher PRS-CD and PRS-IBD.ConclusionsGut dysmotility, along with pro-inflammatory intestinal profiles, and greater genetic predisposition to IBD were observed in PD patients with worse non-motor symptoms. Monitoring intestinal biomarkers may help identify PD patients for targeted interventions.
Visual hallucinations in Parkinson's disease are associated with deficits in social perception.
Albert L, Vehar N, Potheegadoo J … +2 more , Bernasconi F, Blanke O
J Parkinsons Dis · 2025 Jun · PMID 40320762 · Publisher ↗
BackgroundMost structured visual hallucinations (VH) in Parkinson's disease (PD) involve animate-social objects, yet current theories fail to account for the prominent social component of VH in PD.ObjectiveTo study socia...
BackgroundMost structured visual hallucinations (VH) in Parkinson's disease (PD) involve animate-social objects, yet current theories fail to account for the prominent social component of VH in PD.ObjectiveTo study social perception in PD patients with VH in a behavioral task and its relationship with social traits such as perceived social isolation and anthropomorphism (tendency to ascribe human-like characteristics to non-human stimuli).MethodsIn this online web-based study, 28 PD with visual hallucinations (PD-VH), 55 PD patients without hallucinations (PD-nH), and 45 age-matched healthy controls (HC) performed a visual social task (human numerosity estimation), a control task, and filled an anthropomorphism and a loneliness questionnaire.ResultsOur data reveal a deficit in social visual perception characterized by a larger overestimation bias in human numerosity estimation in PD-VH versus control PD-nH and HC. Moreover, PD-VH had higher social traits of anthropomorphism and loneliness versus control PD-nH and HC and the overestimation bias was absent for non-human control stimuli.ConclusionsThese data describe a stronger social visual deficit and higher social traits in PD patients with VH, suggesting that neurodegenerative changes in PD-VH predominantly affect structures involved in social visual perception.
Early thinking palliative care for people with Parkinson's disease: A thematic synthesis based on a systematic mixed-methods review.
Garon M, Weck C, Leta V … +19 more , Dijkstra BW, Muente C, Gentile G, Trivedi D, Groot MM, Lorenzl S, Odin P, Konitsiotis S, Pedrosa DJ, Fotiadis DI, Meinders MJ, Bloem BR, Schrag AE, Grover L, Taba P, Ray Chaudhuri K, Antonini A, Paal P, PD_Pal consortium
J Parkinsons Dis · 2025 Jun · PMID 40320755 · Publisher ↗
BackgroundParkinson's disease is a progressive neurodegenerative disorder. Awareness and the evidence supporting the merits of palliative care (PC) approaches to people with Parkinson's disease (PwP) are increasing.Objec...
BackgroundParkinson's disease is a progressive neurodegenerative disorder. Awareness and the evidence supporting the merits of palliative care (PC) approaches to people with Parkinson's disease (PwP) are increasing.ObjectiveThis review aimed to address four key questions related to PC for PwPs and their caregivers: i) What are the indicators for timely access to PC? ii) When should PC be introduced? iii) What are the current care models for providing PC? iv) What are the barriers and facilitators at the organizational level?MethodsA systematic literature search was conducted in PubMed, CINAHL, Cochrane, EMBASE, and MEDLINE (2006-2024). Six reviewers independently screened abstracts and full texts, and thematic synthesis was applied to develop analytical themes. Reporting followed PRISMA guidelines.ResultsOut of 894 studies, 70 were included. PwPs were infrequently referred to PC services, and while several referral criteria were identified, no consensus emerged. Barriers to accessing PC included insufficient information, inadequate education, difficulties determining referral timing, limited home-based care options, inconsistent provider support, and disparities linked to socioeconomic and cultural factors. Facilitators included improved care coordination and education for PwPs, caregivers, and healthcare providers. Effective PC models were identified, including home-based, hospital-based, and community-based approaches, which improved quality of life and reduced healthcare costs.ConclusionsEstablishing consensus on referral timing and criteria is essential for integrating PC into Parkinson's disease care. Overcoming barriers requires enhanced education, better care coordination, and targeted interventions to address disparities, ensuring comprehensive, patient-centred care for PwPs and their caregivers.
One-year practice effects predict long-term cognitive outcomes in Parkinson's disease.
Avila Pérez S, Koppelmans V, Duff KM … +1 more , Ruitenberg MF
J Parkinsons Dis · 2025 Jun · PMID 40302413 · Full text
Predicting which individuals with Parkinson's disease (PD) will develop cognitive deficits is challenging, but important towards selecting those individuals at higher risk of progression for personalized early interventi...
Predicting which individuals with Parkinson's disease (PD) will develop cognitive deficits is challenging, but important towards selecting those individuals at higher risk of progression for personalized early intervention and enriching samples for clinical trials of disease modifying agents. To examine whether practice effects on cognitive tests across one-year are predictive of eventual cognitive impairment (CI) and dementia (PDD) in individuals with PD. Individuals with PD ( = 549) from the PPMI database who were cognitively intact at baseline were included for analysis. The Montreal Cognitive Assessment (MoCA) was administered at baseline and during annual follow-up visits over at least five years to determine if participants remained intact (MoCA ≥ 26) or developed CI (MoCA ≤ 25) or dementia (MoCA ≤ 21). Participants also completed a neuropsychological battery at baseline and again after a one-year interval. Practice effects on the cognitive tests across one-year were quantified with standardized regression-based change scores using PPMI data from cognitively intact subjects without PD. Based on MoCA scores, 39% of patients developed CI and 10% developed PDD during the study. Linear regressions revealed smaller practice effects across one year in people with PD than in controls. Within the PD group, Cox regression analyses showed that smaller practice effects on tests of various cognitive domains were associated with an increased risk for CI. For PDD, only practice effects on a measure of processing speed significantly predicted cognitive outcomes. These findings demonstrate that practice effects have prognostic value in long-term cognitive outcomes in PD. This has important implications for clinical care and research, as one-year practice effects could help identify individuals at risk for CI and PDD and enrich samples for future clinical trials. Limitations of the present study pertain to the classification of cognitive impairment on the basis of a screening instrument (i.e., the MoCA) without evidence of the absence/presence of functional impairment, and the clinical utility of the one-year interval.
Dementia risk prediction in early Parkinson's disease: Validation and genetic integration of the Montreal Parkinson risk of dementia scale (MoPaRDS).
Szwedo AA, Dalen I, Lawson RA … +12 more , Yarnall AJ, Pedersen KF, Macleod AD, Counsell CE, Bäckström D, Forsgren L, Camacho M, Williams-Gray CH, Tysnes OB, Alves G, Maple-Grødem J, Parkinson's Incidence Cohorts Collaboration
J Parkinsons Dis · 2025 Jun · PMID 40302388 · Publisher ↗
BackgroundPrediction models for dementia in Parkinson disease (PD) are needed to better identify high-risk patients, but existing risk models often lack validation in early-stage PD, when prognosis is most challenging.Ob...
BackgroundPrediction models for dementia in Parkinson disease (PD) are needed to better identify high-risk patients, but existing risk models often lack validation in early-stage PD, when prognosis is most challenging.ObjectiveThis study aims to validate the Montreal Parkinson Risk of Dementia Scale (MoPaRDS) in six population-based cohorts of newly diagnosed PD and to evaluate if incorporating genetic factors ( and ) enhances its performance.MethodsWe calculated MoPaRDS scores for 1108 newly diagnosed PD patients, and MoPaRDS + + for the 941 patients with complete genetic data. We assessed the scores' performance in predicting dementia diagnosed over 10 years using time-dependent receiver operating characteristic (ROC) curves.ResultsOf the 1108 patients (mean age 69.5 ± 10.0 years; 61.0% men), 350 (31.6%) developed dementia. The area under the time-dependent ROC curve (AUC) was 0.79 for MoPaRDS and 0.80 for MoPaRDS + + Subdividing patients based on their MoPaRDS scores revealed annual observed risks of PDD of 39.4% (n = 8; high risk-), 11.4% (n = 176; intermediate risk-), and 5.0% (n = 942; low risk-group). With the suggested cutoff of ≥4, MoPaRDS had a sensitivity of 21.7% and specificity of 94.9%. Including the genetic items improved the sensitivity to 36.4% while maintaining comparable performance for specificity (91.5%).ConclusionsMoPaRDS demonstrates high specificity but limited sensitivity in early PD, highlighting that a one-size-fits-all approach is inadequate for predicting dementia risk in PD across different disease stages. Integrating genetic items increases sensitivity and identifies more newly diagnosed patients at higher risk of dementia, and may be a useful approach to assist dementia risk assessment in early-stage PD.
Use of β-adrenoreceptor drugs and Parkinson's disease incidence in women from the French E3N cohort study.
Nguyen TTH, Fournier A, Courtois É … +8 more , Artaud F, Tubert-Bitter P, Severi G, Lee PC, Roze E, Ahmed I, Thiébaut AC, Elbaz A
J Parkinsons Dis · 2025 Jun · PMID 40302366 · Publisher ↗
BackgroundExperimental and observational studies suggest that β-adrenoreceptor drugs (β2-agonists/β-antagonists) are associated with Parkinson's disease (PD) risk. Previous epidemiological studies may be hampered by reve...
BackgroundExperimental and observational studies suggest that β-adrenoreceptor drugs (β2-agonists/β-antagonists) are associated with Parkinson's disease (PD) risk. Previous epidemiological studies may be hampered by reverse causation/confounding.ObjectiveWe examined the association of β-adrenoreceptor drugs with PD incidence, while addressing reverse causation and confounding in the E3N cohort study (2004-2018) using a new-user design.MethodsIncident β2-agonists/β-antagonists users were identified through drug claims databases. Incident PD was ascertained using multiple sources and validated by experts. Drugs-PD associations were assessed using time-varying Cox proportional hazards models adjusted for multiple confounders. Main analyses used a 5y-exposure lag to address reverse causation; sensitivity analyses used a 2y-lag or no lag. We set up a nested case-control study to compare trajectories of β2-agonists/β-antagonists prescriptions before diagnosis using logistic mixed models.ResultsAnalyses for β2-agonists were based on 81,890 women; 15,169 started using β2-agonists and 579 developed PD. PD incidence was 36% lower (hazard ratio = 0.64, 95% confidence interval = 0.41-0.98; p-trend = 0.04 for the number of claims) in users of long-acting/ultra-long-acting β2-agonists (LABAs/ultra-LABAs) compared to never users. There was no significant association for β2-agonists overall and short-acting β2-agonists. Analyses for β-antagonists were based on 75,896 women; 13,081 started using β-antagonists and 552 developed PD. PD incidence was similar in ever and never users in analyses with a 5y-lag but was higher in ever than never users in analyses with 2y-lag or no lag.ConclusionsIncident use of LABAs/ultra-LABAs is associated with lower PD incidence in women. Conversely, the association between β-antagonists and PD in women is likely due to reverse causation.
Preparing for Parkinson's disease prevention trials: Current progress and future directions.
Bouhadoun S, Delva A, Schwarzschild MA … +1 more , Postuma RB
J Parkinsons Dis · 2026 Jul · PMID 40289581 · Publisher ↗
In recent decades, numerous clinical trials have aimed to delay or prevent Parkinson's disease (PD) progression. Despite the theoretical promise and encouraging preclinical data, none have shown clear efficacy in slowing...
In recent decades, numerous clinical trials have aimed to delay or prevent Parkinson's disease (PD) progression. Despite the theoretical promise and encouraging preclinical data, none have shown clear efficacy in slowing or preventing PD progression, related to several key limitations. Conventional motor and non-motor scales often fall short in detecting early disease changes, while the heterogeneity of PD phenotypes complicates treatment efficacy. The timing of interventions is also critical, as most trials target patients already in advanced stages of neurodegeneration. A deeper understanding of the preclinical phase and the emergence of new pathological frameworks have shifted the focus toward preventing the onset of clinical PD. Recent advances in biomarker research, including tissue, fluid, and imaging markers, are poised to transform PD research by improving patient selection, stratification, and disease progression monitoring. New biologically grounded frameworks for classifying synucleinopathies aim to distinguish biological subtypes from clinical phenotypes, enabling more targeted prevention trials. Successful PD prevention trials will require early enrollment of individuals at the highest risk, employing low-risk personalized interventions, with biomarkers or sensitive clinical markers as endpoints. Early involvement of key stakeholders will be essential to ensure that trials are timely, ethically sound, and aligned with the needs of the PD community.
From past to future: Digital approaches to success of clinical drug trials for Parkinson's disease.
Cong C, Milne-Ives M, Ananthakrishnan A … +2 more , Maetzler W, Meinert E
J Parkinsons Dis · 2026 Jul · PMID 40289580 · Publisher ↗
Recent years have seen successes in symptomatic drugs for Parkinson's disease, but the development of treatments for stopping disease progression continues to fail in clinical drug trials, largely due to the lack of clin...
Recent years have seen successes in symptomatic drugs for Parkinson's disease, but the development of treatments for stopping disease progression continues to fail in clinical drug trials, largely due to the lack of clinical efficacy of drugs. This may be related to limited understanding of disease mechanisms, data heterogeneity, poor target screening and candidate selection, challenges in determining optimal dosage levels, reliance on animal models, insufficient patient participation, and lack of drug adherence in trials. Most of the recent applications of digital health technologies and artificial intelligence (AI)-based tools focused mainly on stages before clinical drug trials. Recent applications used AI-based algorithms or models to discover novel targets, inhibitors and indications, recommend drug candidates and drug dosage, and promote remote data collection. This paper reviews the state of the literature and highlights strengths and limitations in digital approaches to drug discovery and development for Parkinson's disease from 2021 to 2024, and offers recommendations for future research and practice for the success of drug clinical trials.
Dopamine-responsive post-anoxic parkinsonism.
Liu T, Ahlskog JE, Bower J … +2 more , Kantarci O, Savica R
J Parkinsons Dis · 2025 Jun · PMID 40270087 · Publisher ↗
BackgroundParkinsonism following hypoxic ischemic damage of the basal ganglia is an uncommon phenomenon that has been infrequently reported. However, only a few cases have noted improvement of symptoms with dopaminergic...
BackgroundParkinsonism following hypoxic ischemic damage of the basal ganglia is an uncommon phenomenon that has been infrequently reported. However, only a few cases have noted improvement of symptoms with dopaminergic therapy. We report the clinical and imaging features of five patients with post-anoxic parkinsonism responsive to dopamine supplementation.ObjectiveTo describe a retrospective case series of five cases of dopamine-responsive post-anoxic parkinsonism.MethodsWe identified all the cases using the Mayo Clinic Data Management System utilizing advanced data explorer search engine for any patients evaluated for post anoxic parkinsonism and its associated acronyms from 2000-2024. Clinical features, neuroimaging, medication trials, and responses were obtained from chart review of identified patients.ResultsFive patients met the inclusion criteria. All patients underwent anoxic events followed by development of parkinsonism. Patients exhibited parkinsonism described as combinations of bradykinesia, rigidity, tremor, and postural instability. All patients underwent evaluation by a neurologist, MRI imaging, and treatment by dopaminergic agents. Of the five patients, four received carbidopa/levodopa whereas one received a dopamine agonist. All patients were clinically followed for a median of approximately 4 years and showed improvement in parkinsonism.ConclusionsParkinsonism following a hypoxic ischemic insult is a rare occurrence but response to dopaminergic therapy in those cases is even more scarcely described. Our cases series provides important implications for treatment options for patients with post anoxic parkinsonism.
The fixel GI Parkinson's research and integrated support model (PRISM).
Hey G, Amaris M, Beke M … +7 more , Walker-Pizarro N, Rogers C, Vedam-Mai V, Dorsey R, Herndon N, Okun MS, Ramirez-Zamora A
J Parkinsons Dis · 2025 May · PMID 40241494 · Publisher ↗
BackgroundThe complexity of gastrointestinal (GI) disorders associated with Parkinson's disease (PD) and the significant interactions between GI medications and the dopaminergic axis necessitates expert management. The i...
BackgroundThe complexity of gastrointestinal (GI) disorders associated with Parkinson's disease (PD) and the significant interactions between GI medications and the dopaminergic axis necessitates expert management. The integrated care model for disorders of the brain-gut interaction (DBGI) has advantages, however, has not been applied in concurrent DBGI and PD.ObjectiveTo test the hypothesis that our Parkinson's Research and Integrated Support Model (PRISM) will reduce symptom severity and improve the quality of life (QOL) in patients with GI symptoms associated with PD.MethodsPatients with refractory GI symptoms referred to the PRISM clinic were evaluated and treated by the integrated efforts of movement disorder specialists, neurogastroenterologists, dietitians, occupational therapists, speech-swallow therapists, and neuroscientists. Patients underwent a battery of GI symptoms and QOL questionnaires and personalized actionable biomarkers (motility testing and swallowing studies). Inflammatory markers and stool tests were collected. An individualized standard of care treatment was established based on the specific DBGI diagnosis uncovered during the PRISM evaluation.Results44 adult PD patients with GI complaints were evaluated. The most common symptoms included constipation (97%), dysphagia (61%), and gastroesophageal reflux (34%). Actionable biomarkers were highly positive revealing esophageal dysmotility (20/21, 95%), slow-transit constipation (40/42, 90%), intestinal methanogen overgrowth (7/8, 87%), gastroparesis (17/20, 85%), oropharyngeal dysphagia (28/44, 63%), and dyssynergic defecation (27/42, 61%). GI symptom severity and QOL significantly improved ( < 0.05) as measured by all questionnaires.ConclusionsMore severely affected patients with Parkinson's treated with the Fixel PRISM approach showed significant improvements in GI symptom frequency, severity, and QOL.
Recent advances of transcranial electrical stimulation in healthy aging and Parkinson's disease: Effects on dual tasking.
Putzolu M, Botta A, Cosentino C … +7 more , Mezzarobba S, Bonassi G, Ravizzotti E, Terranova S, Lagravinese G, Pelosin E, Avanzino L
J Parkinsons Dis · 2025 Jun · PMID 40241492 · Publisher ↗
Dual tasking involves the simultaneous execution of two actions. In the context of healthy aging and neurodegenerative disorders, such as Parkinson's disease (PD) engagement in dual tasking frequently results in impaired...
Dual tasking involves the simultaneous execution of two actions. In the context of healthy aging and neurodegenerative disorders, such as Parkinson's disease (PD) engagement in dual tasking frequently results in impaired gait or upper limb performance, thereby affecting functional independence. Transcranial electrical stimulation is a non-invasive technique able to modulate brain activity, which might represent a potential tool for reducing dual task interference. The goal of this review is to provide a comprehensive summary of the most recent findings about the use of transcranial electrical stimulation in improving dual tasking in the elderly and people with PD, including considerations about the optimal stimulation parameters. Differences in terms of stimulation protocols emerged across the included studies. Among transcranial electrical stimulation techniques, transcranial direct current stimulation (tDCS) was the most frequently employed. Currently, using tDCS to target dorsolateral prefrontal cortex either alone or in a multi-site fashion, along with a concurrent complex task, appears to be the most promising method for reducing dual task interference. Nevertheless, the lack of control over interindividual variability, the heterogeneity in outcome measures assessing dual tasking, and the variations in protocol elements like the frequency and the number of sessions prevented us from drawing definitive conclusions about the best paradigm.
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