To investigate whether antidiabetic drugs have a biological basis to be repurposed in PD prevention, we applied a drug target Mendelian randomization framework to assess associations between genetic variation in antidiabetic drug targets and PD risk or age at onset (AAO). Instrumental variables (IVs) were derived from GWAS summary statistics on fasting glucose (FG), glycated...
Advances in deep brain stimulation lead technology have created new opportunities for multi-site network modulation, including applications for freezing of gait, but systematic strategies for trajectory planning are lacking. We evaluated trajectories targeting the subthalamic nucleus (STN) and the simultaneous engament of the substantia nigra (SN), specifically its pars...
Emerging evidence indicates that movement disorders arise from symptom-specific rather than disease-specific brain network dysfunctions that can be influenced through targeted neuromodulation. Such networks are widely mapped using normative connectome analyses from lesion and stimulation sites. Here, we used [18F]-fluorodeoxyglucose (FDG)-PET in 14 essential tremor patients...
Accurate subthalamic beta activity could guide deep brain stimulation programming in Parkinson’s disease, but bipolar recordings complicate contact selection. In 39 patients, we validated three methods to estimate pseudo-monopolar beta power. Distance-weighted methods (Euclidean, Strelow) agreed consistently with the externalized “ground-truth” beta distribution. Maximal beta...
Epidemiological studies suggest an association between Parkinson’s disease (PD) and ulcerative colitis (UC), yet the molecular programs potentially linking these disorders remain poorly defined. Here, we integrated curated disease-gene resources with publicly available blood transcriptomic datasets to identify shared molecular features across PD and UC. We identified 320 shared...
This Comment provides methodological insights and clinical perspectives on real-world outcomes of device-aided therapies in Parkinson’s disease.
The rising prevalence of Parkinson’s disease has created an urgent need for brain activity markers guiding diagnosis and treatment strategies. While abnormal basal ganglia activity is known to synchronise with specific cortical regions, the temporal dynamics and cortical network architecture of this coupling remain unclear. To address this, we analysed simultaneous...
Anxiety is a prevalent non-motor symptom of Parkinson’s disease (PD), yet treatment options remain limited. This randomized, double-blind, placebo-controlled trial evaluated the effects of a 12-week probiotic supplement containing nine bacterial strains (Bifidobacterium bifidum W23, Bifidobacterium lactis W51 and W52, Lactobacillus acidophilus W37, Levilactobacillus brevis W63...
Deep brain stimulation (DBS) improves motor function in Parkinson’s disease, yet programming remains labor-intensive and largely subjective. We evaluated a smartphone video-based kinematic framework (StimVision) for objective, within-session optimization of DBS settings and characterization of therapeutic motor signatures. Fifteen patients with subthalamic DBS performed...
Regional brain atrophy has been observed in dementia with Lewy bodies (DLB), yet determinants of regional vulnerability remain unclear. Using imaging transcriptomics, we examined whether normative gene expression patterns relate to regional atrophy in DLB. We included 164 DLB patients (49 women) and 164 age- and sex-matched healthy controls from three European centres and the...
Individuals with Parkinson’s disease (PD) often experience a misalignment between their perceived and actual balance ability, known as balance discordance, which has been associated with falls. We examined whether high-intensity balance and gait training (HiBalance) alters balance discordance in individuals with PD, and whether baseline sedentary behavior influences these changes...
We investigated the basis and clinical correlates of a negative cerebrospinal fluid (CSF) alpha-synuclein (α-syn) seed amplification assay result in patients with a clinical diagnosis of sporadic or GBA1-associated PD formulated by movement disorder specialists. Out of 473 participants with a confirmed PD diagnosis at the last follow-up, 62 (13.1%) were α-syn negative. Among them...
Cognitive domains are central to diagnosing cognitive impairment in people with Parkinson’s disease (PwPD), yet are defined by expert consensus and cross-sectional data that assume temporal stability. This study examined whether cognitive domains remain stable or reorganize dynamically over time in PwPD. Using dynamic exploratory graph analysis, we analyzed 19 cognitive test...
Parkinson’s disease (PD) is a progressive neurodegenerative disease caused by the loss of dopaminergic neurons; however, growing evidence indicates the widespread involvement of cortical regions underlying motor and non-motor symptoms. In this study, we evaluated multiparametric mapping (MPM) as a non-invasive imaging technique for the detection of microstructural brain...
5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are epigenetic modifications increasingly recognized for their roles in Parkinson’s disease (PD). In this study, we profiled 5mC and 5hmC in blood samples from individuals with PD to explore their relevance to disease status and progression. We observed significantly reduced global 5hmC levels in peripheral blood...
Several studies have investigated the prodromal factors for early diagnosis of Parkinson’s disease (PD). Instrumental activities of daily living (IADL) involve both motor and non-motor functions, and has been used as a screening tool for dementia. This study aimed to examine the association between IADL dependency and PD incidence and identify specific IADL items linked to an...
The gut microbiome is believed to play an important role in the development and onset of Parkinson’s disease (PD). While human studies report differences in gut microbiota between PD individuals and healthy controls, it is unclear whether preclinical animal models show similar patterns. We performed a systematic review and Bayesian regularised meta-analysis of preclinical PD...
Motor dysfunction in Parkinson’s disease (PD) has been linked to widespread oscillatory changes within the basal ganglia-thalamic-cortical network, particularly in the beta frequency range. However, the evolution of cortical neurophysiological alterations and their relationship to clinical progression remain poorly understood. We conducted a longitudinal resting-state...
It is postulated that microglial cells interact with dopaminergic (DA) neurons of the substantia nigra pars compacta (SNpc), playing a critical role in Parkinson’s disease (PD) neurodegeneration. However, the specific mechanisms by which microglial reactivity is triggered remain unclear. Experimental models of PD in mice indicate that phagocytosis drives the elimination of...
In Parkinson’s disease and dementia with Lewy bodies, aggregated and phosphorylated α-synuclein appears in select neurons throughout cortical and subcortical regions, but little is currently known about why certain populations are selectively vulnerable. Here, using imaging spatial transcriptomics (IST) coupled with downstream immunofluorescence for α-synuclein phosphorylated at...
Aging is the most significant risk factor for Parkinson’s disease (PD), yet its role remains underexplored. The International Network for Parkinson’s Disease Modelling and Aging (PD-AGE), funded by the Michael J. Fox Foundation, was established to address these challenges. Through collaborative efforts, the PD-AGE mouse-model working group developed a roadmap to prioritize mouse...
Parkinson’s disease (PD) is the fastest-growing neurodegenerative disease in the world1. Gastrointestinal (GI) dysfunction can occur decades before motor impairments and in up to 80% of individuals living with PD2,3,4. We investigated peripheral relationships that may underlie mechanisms along the gut–blood axis that contribute to PD progression. Single-cell multiomic spatial...