npj Parkinson's Disease

BackgroundSensitive outcome measures are critical for evaluating the efficacy of novel treatments for Parkinson disease (PD). Recently, we demonstrated that a tremor detection algorithm could reliably detect and quantify real-life PD tremor from wearable sensor data. Here, we assess the sensitivity to change of sensor-derived daily-life tremor measures over two years in an unmedicated and medicated cohort of persons with early PD. MethodsWe used two-year continuous wrist sensor data (median wea...

BackgroundIdiopathic REM sleep behavior disorder (iRBD) and hyposmia are the strongest clinical indicators of prodromal Parkinsons disease, reflecting distinct proposed pathways of -synuclein pathology propagation. According to the body-first/brain-first model, iRBD represents a body-first phenotype with early brainstem involvement, whereas hyposmia may reflect a brain-first phenotype with early limbic involvement. We therefore hypothesized that these markers would show distinct fiber-specific w...

Body-first Lewy body disease (LBD) is hypothesized to begin in the peripheral autonomic nervous system, years before nigrostriatal involvement. Isolated REM sleep behaviour disorder (iRBD) is considered prodromal body-first LBD, but the duration of the prodromal phase remains unknown. We aimed to determine the progression rate of cardiac sympathetic denervation using [123I]meta-iodobenzylguanidine (MIBG) scintigraphy and employ the resulting curves to estimate the prodromal period of body-first ...

Importance: Dementia is common in Parkinson's disease (PD), causing greater disability than other symptoms, but varies in timing. Although visual deficits are linked with PD dementia, how these interact with genetic factors to predict PD dementia has not been characterised. Objective: To investigate whether visual deficits and genetic factors predict PD dementia. Design: Large prospective longitudinal case-control study, mean follow-up 32.7 (SD=12.3) months. Setting: Cases were recruited between...

Parkinsons disease (PD) is characterized by substantial heterogeneity in progression patterns, posing major challenges for individualized prognosis and clinical management. This study presents Structure-Function Neural Field Alignment and Multi-View Distillation (SFNFA-MVD), a novel deep learning framework that integrates structural, functional, and diffusion MRI to predict motor trajectories and identify progression subtypes of PD. SFNFA-MVD is built around two complementary components: a neura...

Olfactory decline is a well-established aspect of Parkinsons disease (PD) and is considered one of its earliest signs, often preceding motor symptoms by years to decades. However, because olfactory impairment is also common in healthy aging and other medical conditions, current olfactory tests that score performance (odor detection, discrimination, and identification) lack disease specificity. In contrast to performance scores, olfactory perceptual fingerprints are derived from odor ratings and ...

Parkinsons disease (PD) involves variable patterns of brain atrophy in different motor and cognitive regions that differ across patients in both location and progression rate. Existing clinical tools and single-modal imaging methods can be difficult to analyze how individual patients atrophy will progress. Thus, we developed and evaluated deep learning models capable of understanding the pattern of 216 features of PD patients and predicting future regional brain atrophy in individuals with PD us...

BackgroundLoss of smell commonly predates the diagnosis of Parkinsons disease (PD). However, smell loss has multiple causes, and the relationship between idiopathic anosmia (IA) and PD remains incompletely understood. ObjectivesTo assess the presence of prodromal features of PD in individuals with IA and to examine the relationship between anosmia duration and prodromal features. MethodsWithin the PREDICT-PD study, patients with IA investigated at specialist smell clinics were compared with he...

IntroductionSex has emerged as a key factor shaping serum metabolomic profiles in idiopathic Parkinsons disease (PD). However, it remains unclear whether sex differences influence circulating metabolic signatures in patients with specific PD-related gene mutations compared to age-matched healthy controls (HCs). MethodsWe conducted an untargeted 1H NMR-based metabolomic analysis of serum in a clinically defined cohort of patients with genetic forms of PD (n = 119) and age- and sex-matched HCs (n...

Environmental neurotoxins have been implicated in the pathogenesis of Parkinsons disease (PD), with Agent Orange (AO) recognized as a presumptive service-connected exposure among U.S. Veterans. However, prospective data examining potential clinical differences associated with AO exposure remain limited. We conducted a multicenter prospective cohort study of U.S. Veterans with PD to compare demographic and clinical characteristics between individuals with and without a history of AO exposure. Cl...

ObjectiveMotor decline is a hallmark of Parkinsons disease (PD) and biological aging. While epigenetic clocks measure systemic biological aging, their specific relationship with neuromotor function in the context of aging and neurodegeneration remains under-characterized. This study utilized data from the Parkinsons Progression Markers Initiative (PPMI) to examine the relationships between multiple DNA methylation-based epigenetic aging measures and motor impairment across distinct domains. Met...

Parkinsons Disease (PD) is the most prevalent neurodegenerative disorder after Alzheimers, yet its diagnosis largely relies on subjective clinical assessments. Thus, this study proposes a systematic, data-driven approach to accurately classify PD patients using heterogeneous risk factors along with efficient machine learning. Six machine learning algorithms, Support Vector Machine(SVM), Random Forest(RF), Extreme Gradient Boosting(XGBoost), Logistic Regression(LR), K-Nearest Neighbour (KNN), and...

BackgroundParkinsons disease (PD) is characterized by widespread neurodegeneration across neuromodulatory systems, profoundly affecting cortico-basal ganglia-thalamic loops. The resulting cortical alterations can be detected with electroencephalography (EEG). Emerging evidence shows that aperiodic EEG components provide biologically meaningful information that complements the periodic features traditionally examined. Therefore, dissociating periodic and aperiodic components may yield sensitive a...

Distinguishing atypical parkinsonian disorders (APS) from Parkinsons disease (PD) remains challenging due to overlapping clinical features, yet accurate differentiation is critical for prognosis and treatment. Here, we employed multi-model diffusion MRI (dMRI) analysis to characterize microstructural alterations across corticobasal syndrome (CBS), progressive supranuclear palsy-Richardson syndrome (PSP-RS) and PD, with the aim of identifying which dMRI model provides optimum differentiation. We ...

Parkinsons disease is a progressive neurological disorder characterized by motor impairments whose severity is commonly assessed using the Unified Parkinsons Disease Rating Scale (UPDRS). Although clinically established, UPDRS assessment requires in-person evaluation by trained specialists and is inherently subjective, limiting its suitability for frequent monitoring. Speech production is affected early in Parkinsons disease and provides a non-invasive modality for remote symptom assessment. In ...

BackgroundSpeech abnormalities are common in Parkinsons disease (PD). Machine learning (ML) offers potential for objective and scalable speech-based diagnostics. This study introduces an explainable ML pipeline that leverages a novel vowel articulation-based composite input to detect PD and identify phoneme-level biomarkers. MethodsTwo publicly available datasets of PD speech recordings were analyzed. Sustained vowel articulations were converted into log-mel spectrograms either individually or ...

We describe the design of the first non-pharmacological prevention trials of Parkinsons Disease worldwide: the randomised controlled Slow-SPEED trials. The three trials examine the feasibility and preliminary efficacy of a gamified, remotely administered exercise intervention vs. active control program over 18-36 months in the Netherlands (n=110), United Kingdom (n=110) and United States (n=600). Each trial focuses on a complementary prodromal subgroup: isolated/idiopathic REM sleep behavioural...

BackgroundMelanocortin 1 receptor (MC1R) is a key regulator of pigmentation. Previous studies have linked MC1R loss-of-function variants to increased risk for Parkinsons disease (PD); however, whether they are associated with PD progression remains unknown. Using data from the Parkinsons Progression Markers Initiative (PPMI) cohort, we aimed to test whether MC1R loss-of-function variants, especially those previously associated with an increased risk of PD, are associated with PD progression and ...

BackgroundAggregation of -synuclein is a central pathological feature of Parkinsons disease (PD), yet reliable and broadly applicable fluid biomarkers reflecting disease-relevant -synuclein biology remain limited. We aimed to establish acetylated -synuclein (Ac-Syn), the predominant proteoform in vivo, as a novel biomarker for PD and to evaluate its diagnostic utility based on a sensitive immunoassay. MethodsUsing a single molecule array technique capable of quantitatively detecting N-terminall...

Asymmetric arm swing reduction is a hallmark of early-stage Parkinsons disease (PD). We evaluated wrist sensor-based arm swing measures during free-living gait as digital progression biomarkers in 623 early-stage PD participants and 50 controls monitored continuously for one year (controls) or two years (PD). Biweekly measures were extracted from gait segments without other arm activities. Arm swing measures were reduced in PD, reduced on the most affected side, moderately correlated with clinic...