Search Results (1,559)

According to the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder among older adults, surpassed only by Alzheimer’s disease. PD is characterized by a heterogeneous combination of motor and non-motor symptoms, with involuntary movements constituting a central clinical defining feature. The prodromal phase presents substantial diagnostic challenges, as early symptoms are often mild, nonspecific, and commonly misinterpreted because overt motor signs are absent. Significantly, these early alterations can precede formal diagnosis by up to two decades, highlighting the urgent need for effective early detection strategies. In this work, we propose a functional Magnetic Resonance Imaging (fMRI)-based image-processing and machine learning framework for early detection of PD. Statistical features are extracted to train a set of 25 machine learning kernels, from which the most accurate model is selected. We then apply the Minimum Redundancy Maximum Relevance (mRMR) algorithm to identify the most descriptive fMRI frames for each subject. We introduce a hierarchical classification strategy: an initial binary classification to distinguish control subjects from prodromal + PD cases, followed by a second binary classification to discriminate between Prodromal and PD. The experimental results demonstrate a maximum precision of $96.3$% with 16 axial slices and $86.4$% with a single slice, indicating the effectiveness of the preprocessing strategy and its potential as a non-invasive biomarker for early PD detection, even with reduced input data. These findings suggest that high classification performance can be achieved with a limited number of fMRI slices, facilitating data acquisition and reducing subject burden in clinical studies. Full article

Objective: To evaluate the sustained real-world effectiveness and safety of catechol-O-methyltransferase (COMT) inhibitors added to levodopa in patients with Parkinson’s disease (PD) presenting early motor fluctuations. Methods: REONPARK is an ongoing, multicenter, prospective observational study conducted in Spain. Adult patients with PD and end-of-dose motor fluctuations for <2 years initiating a COMT inhibitor were included. Outcomes assessed at 3, 6, and 12 months included Clinician and Patient Global Impression of Change (CGI-C, PGI-C), Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Wearing-off Questionnaire (WOQ-19), Non-Motor Symptoms Scale (NMSS), Parkinson’s Disease Questionnaire-8 (PDQ-8), and safety. This article presents the 3-, 6-, and 12-month planned interim analysis of the study. Results: A total of 143 patients were included (99.3% treated with opicapone), of whom 138, 131, and 89 patients completed the 3, 6, and 12 months of follow-up, respectively. Levodopa doses remained stable in most patients (73% at 12 months). Significant and sustained improvements were observed in MDS-UPDRS Parts III and IV scores, as well as the total MDS-UPDRS score over 12 months, with greater likelihood of Part IV improvement in patients receiving <4.5 mg/kg/day of levodopa. OFF time decreased by 1.6–2.0 h from baseline. ON-time quality was maintained over time with 97.7% of patients reporting no or minimal functional impact from dyskinesia, while 47.7% of patients had no impact from motor fluctuations and 36.4% of patients no longer experienced OFF periods at 12 months. PDQ-8 scores remained stable and no overall benefit on total non-motor symptoms burden was demonstrated, despite improvements in selected domains among patients with a higher baseline non-motor symptoms burden. WOQ-19 scores improved significantly. Conclusions: In PD patients with early motor fluctuations, opicapone initiation was associated with sustained improvements in motor outcomes and reduced OFF time, and maintained the ON-time quality over 12 months, with stable levodopa dosing. Full article

Parkinson’s disease (PD) is a clinically and biologically heterogeneous neurodegenerative disorder in which variable symptom profiles, progression rates, and treatment responses likely reflect distinct but partially convergent pathogenic mechanisms. Among these, mitochondrial dysfunction recurs across both familial and sporadic PD; however, this broad concept alone cannot explain disease heterogeneity. To preserve mitochondrial homeostasis, cells rely on a complex mitochondrial quality control (MQC) system that encompasses protein import and proteostasis, redox surveillance, organellar dynamics and positioning, biogenesis, and selective elimination of damaged mitochondria. MQC also depends on coordination with other organelles, particularly the endoplasmic reticulum and lysosomes. In this review, we discuss how different layers of MQC maintain mitochondrial integrity and how these pathways are functionally coupled. We further consider how an MQC-based framework may help explain the clinical heterogeneity of PD, including selective neuronal vulnerability, subtype formation, and divergent disease progression, and how it can frame recent therapeutic advances aimed at biologically stratified intervention. Full article

Background: Parkinson’s disease (PD) is a chronic, slowly progressive, and irreversible neuropathological disorder characterized by the progressive degeneration of specific neurons responsible for producing neurotransmitters essential for motor control. Although PD primarily affects motor function, various non-motor symptoms commonly emerge during the prodromal phase. These include autonomic dysfunction, cognitive and neurobehavioral disorders, and sensory and sleep abnormalities. Notably, speech and voice alterations, particularly hypokinetic dysarthria, are frequent manifestations. This research presents a methodology to distinguish between individuals with PD and healthy controls using voice signals through speech recognition and machine learning (ML) techniques. A dataset comprising 81 voice samples (41 healthy controls and 40 PD patients) was utilized to extract two types of cepstral features: Mel-frequency cepstral coefficients (MFCCs) and subband-based cepstral coefficients (SBCs). These extracted features were used to train and evaluate three ML algorithms: Random Forest (RF), K-Nearest Neighbors (KNN), and Support Vector Machines (SVM). Results: Among the algorithms evaluated, the SVM-SBC model exhibited the highest performance, achieving an accuracy of 79%, a sensitivity of 75.5%, and an Area Under the ROC Curve (AUC-ROC) of 84%. Conclusions: This study highlights the potential of integrating cepstral features with machine learning algorithms to develop reliable, non-invasive tools for the early detection of PD. Full article

Background/Objectives: Intranasal delivery is a promising noninvasive approach to enhance central nervous system drug delivery in Parkinson’s disease (PD), potentially bypassing the blood–brain barrier and minimizing gastrointestinal side effects. This review summarizes clinical trials and translational evidence for intranasal PD therapies by treatment options and intent, highlighting key challenges in efficacy, pharmacokinetics, and safety. Methods: We reviewed human clinical trials, preclinical and pilot studies, and pharmacokinetic investigations of intranasal therapies for PD. Comparisons to established treatments were included in context. Only PD-specific clinical studies were analyzed. Therapies were grouped by rescue, antioxidant/metabolic/hormonal, and biologic or cell-based approaches, with continuous-delivery systems reviewed separately. Results: Intranasal rescue therapies, such as apomorphine, provide rapid improvement during OFF episodes (periods when the effects of PD medications fade and symptoms reappear), but tolerability issues and nasal irritation limit usage. Early-phase studies suggest intranasal delivery enables quick symptom relief and favorable pharmacokinetics, though most trials are small and focus on feasibility. New approaches include antioxidants, neurotrophic factors, gene therapy, and cell-based methods, with advanced formulations enhancing nasal retention and brain uptake. However, more translational evidence and long-term safety data are needed. Conclusions: Intranasal therapies for PD offer rapid rescue and expand options beyond standard drugs. Large, well-designed trials are needed to confirm efficacy, long-term safety, and optimal formulations. Intranasal delivery remains an emerging but potentially transformative strategy requiring further clinical research. Full article

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder causing disabling motor dysfunction and substantial socioeconomic burden. Photobiomodulation (PBM), a noninvasive red/near-infrared light therapy, has shown preclinical promise, but its clinical efficacy and safety in PD remain uncertain. Objectives: To systematically evaluate the efficacy and safety of PBM on motor outcomes in PD. Methods: This PRISMA-compliant systematic review was prospectively registered in PROSPERO (CRD420261411269). Databases were searched through May 2026. Randomized and non-randomized trials in adults with PD were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias (RoB 2.0; ROBINS-I). Where data permitted, random-effects meta-analyses used mean difference (MD) with REML estimation and Hartung–Knapp–Sidik–Jonkman confidence intervals. Results: Eight trials (n = 279) were included, exhibiting substantial heterogeneity in wavelength, device type, stimulation sites, and dosimetry. PBM was safe and well tolerated, with only minor adverse effects. Meta-analysis of four RCTs found no significant effect on MDS-UPDRS-III (MD = −1.37 points, 95% CI: −5.55 to 2.80; I² = 20.6%) or TUG (MD = −0.52 s, 95% CI: −5.03 to 3.99; I² = 55.1%). An exploratory TMWT meta-analysis (k = 2) yielded MD = −0.65 s (95% CI: −1.78 to 0.49; I² = 0.0%), with direction consistently favoring PBM. Individual effect sizes ranged from negligible (d = 0.03–0.06) to small-to-moderate (d = 0.41). Conclusions: PBM appears safe, feasible, and acceptable in PD, but current evidence does not support clinically meaningful motor benefits. Heterogeneous protocols, small samples, and absent target-engagement biomarkers limit definitive interpretation. Well-powered standardized trials with mechanistic endpoints are needed. Full article

Heritability in Parkinson’s disease (PD) may be driven by rare variants (RVs), but genetic data for Chinese cohorts remain limited. We investigated the relationship between RVs and the risk and phenotype of PD by performing targeted exome sequencing of 29 PD candidate genes in 311 late-onset, sporadic Chinese PD patients and 699 local controls. A total of 174 RVs (that were likely deleterious using in silico prediction tools) were identified in 27 of the 29 genes sequenced. Mean RV burden was higher (1.178 vs. 0.478, p = 1.26 × 10⁻²⁴) and HLA-DRB5 p.Val104ArgfsTer26 was enriched in PD patients (0.207 vs. 0.000, p < 0.0003) compared with controls. Gene-based RV carrier status in PD patients was then examined for correlation with phenotypic characteristics. The RV carrier status of LRRK2 and HLA-DRB5 was associated with tremor, SREBF1 with gait disturbance, and SYNJ1 and SCARB2 with motor fluctuations. Earlier onset age and neuropsychiatric symptoms were associated with GBA1 variants. Olfactory deficit, autonomic disturbance, anxiety and depression were associated with variants in SLC44A1, HLA-DRB5, and SCARB2 respectively. Our results demonstrated a prominent RV burden in Chinese PD and illustrated the importance of genetic influence on the risk and phenotype of sporadic PD. Further studies are warranted to correlate these genes with putative pathogenic pathways. Full article

Objectives: Non-pharmacological therapies are a cornerstone of Parkinson’s disease (PD) treatment, but there is not enough evidence of their benefit when delivered altogether online. Our objective was to analyze the efficacy and safety of an online comprehensive care therapy program (OL-CCTP) in people with PD (PwP). Material and methods: This was a proof-of-concept experimental, prospective, 6-month interventional study comparing a PD treatment group (PwP-T) with a control group (PwP-C). The OL-CCTP included group sessions of physical therapy/therapeutic exercise, nutrition, speech therapy, cognitive stimulation, and psychological support (126 sessions over 6 months). The primary outcome was the change in quality of life at 6 months, as measured by the PDQ-39 questionnaire. Mood (Beck Depression Inventory-II [BDI-II]), the non-motor symptom burden (Non-Motor Symptoms Scale [NMSS]), and disability (Schwab and England Activities of Daily Living Scale [ADLS]) were also assessed. Results: Sixty patients (36 PwP-T and 24 PwP-C) completed the assessments. A reduction of 12.9% (from 78.4 ± 17.9 to 68.3 ± 18.7; p < 0.0001) was observed in the PDQ-39 total score in the PwP-T group (p < 0.0001), compared to 1.5% (from 77.8 ± 22.2 to 76.6 ± 27.9; p = 0.438) in the PwP-C group (p = 0.009). The BDI-II and NMSS scores decreased significantly by 13.1% (p = 0.001) and 20.3% (p = 0.046), respectively, in the PwP-T group but not in the PwP-C group. There were no significant changes in ADLS in either group. No adverse events were reported. Conclusions: After 6 months of OL-CCTP, an improvement of 12.9% was observed in the quality of life of patients with PD. Full article

Neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) develop over decades, yet their earliest pathogenic drivers remain poorly understood. Epidemiological and experimental animal studies suggest that disturbances in oral sensorimotor regulation, particularly within trigeminal proprioceptive pathways, may contribute to neural dysfunction long before clinical symptoms emerge. The mesencephalic trigeminal nucleus (MesV), the only primary sensory neuron population located entirely within the central nervous system (CNS), links oral proprioception with brainstem and forebrain networks. Chronic occlusal mismatch, impaired mastication, sleep bruxism, and sleep-disordered breathing may generate persistent sensorimotor prediction errors that destabilize MesV-centered circuits and subsequently recruit the locus coeruleus (LC), the brain’s principal noradrenergic stress nucleus. This review proposes an oral–brain axis model in which chronic MesV-related prediction error signaling engages LC-dependent stress systems, leading to neuroimmune activation, locus coeruleus–asparagine endopeptidase (LC-AEP) pathway engagement, and downstream proteinopathic processes. Sustained LC activity may facilitate microglial priming, reactive astrocytosis, and neuroinflammatory signaling, creating conditions that favor LC-AEP pathway activation and downstream tau pathology. Epidemiological studies associate tooth loss, reduced occlusal support, and impaired mastication with increased dementia risk, while experimental models of prodromal PD demonstrate early trigeminal sensory-processing abnormalities preceding motor symptoms. Together, these findings support the hypothesis that chronic disturbances in oral sensorimotor homeostasis may increase neurodegenerative vulnerability. This framework identifies potential biomarkers and preventive targets, suggesting that modulation of oral function and neuroimmune pathways may help reduce neurodegenerative risk before irreversible neuronal loss occurs. Full article

Parkinson’s disease (PD) is a neurodegenerative disorder caused by the loss of dopaminergic neurons. Its symptoms affect both motor functions—such as bradykinesia, rigidity, resting tremor, and postural instability—and non-motor functions, including neuropsychiatric issues, sleep disorders, and constipation. Drawing on the literature, the following topics were developed and presented: Pathophysiology; Treatment; Neuropsychiatric and Cognitive Function; Sleep Challenges; Exercise and Movement; Striving for Wellness; and Obstacles/Paths Forward. These seven categories form the foundation of this review, which centers on four main areas related to PD: dopamine biology and pathophysiology; management of key motor and non-motor symptoms; strategies for achieving wellness; and unresolved issues in PD. The complexity of PD’s clinical features is highlighted by describing patient–healthcare provider interactions, elucidating disease mechanisms, managing motor and non-motor symptoms, highlighting the benefits of exercise, emphasizing the importance of sleep, addressing mental health challenges and cognitive changes, fostering a hopeful and resilient mindset, potentially slowing disease progression, treating comorbidities, and promoting overall wellness. Although there have been tremendous advances in the basic science and clinical management of PD in recent years, PD remains incurable. Thus, we describe several roadblocks that have hindered progress in understanding PD. Only by integrating historical insights with the latest PD advances can we acquire the knowledge needed to change the disease’s trajectory. Finally, this review aims to provide a meaningful summary for healthcare professionals (and students) caring for patients with PD. Full article

Background and Clinical Significance: Parkinson’s disease (PD) is a progressive neurodegenerative disorder for which nonpharmacological neuromodulatory approaches are being explored as adjunctive strategies. Deep transcranial magnetic stimulation (dTMS) using an H-coil can engage broader and deeper cortical networks than conventional focal coils, although anatomically distant structures are expected to be influenced through network modulation rather than direct electromagnetic stimulation. Case Presentation: We describe a five-patient exploratory case series evaluating clinical measures and cerebral perfusion before and three months after high-frequency dTMS targeting the supplementary motor area (SMA). Clinical outcomes included the Unified Parkinson’s Disease Rating Scale (UPDRS) Parts I-IV, Non-Motor Symptoms Scale (NMSS), Hoehn–Yahr stage, and Timed Up and Go test. Antiparkinsonian medication regimens and doses remained unchanged during the three-month follow-up. Cerebral perfusion was assessed using single-photon emission computed tomography (SPECT) and statistical parametric mapping. No clinical outcome reached nominal statistical significance at follow-up; given the sample size, this should be interpreted as limited statistical power rather than evidence of no effect. At an exploratory voxel-wise threshold of p < 0.001, uncorrected, SPECT identified a 28-voxel cluster of increased regional cerebral blood flow in the right cerebellar cortex (peak MNI coordinates: 22, −38, −44; t = 5.96; z = 3.11). Conclusions: These observations are hypothesis-generating and may reflect network-level modulation of SMA–cerebellar circuitry. Because only five patients were included, no sham-controlled arm was available, and the imaging analysis used an uncorrected exploratory threshold, causal or efficacy claims cannot be made. Larger sham-controlled studies with standardized dose-to-imaging timing, formal neuropsychological assessment, individualized targeting, and prespecified corrected imaging analyses are warranted. Full article

Parkinson’s disease (PD) is a multisystem disorder in which gastrointestinal dysfunction often precedes motor symptoms, yet the molecular links between peripheral stress and central neurodegeneration remain unclear. We investigated whether genes commonly dysregulated in PD and a classic model of intestinal inflammation (IBD) might reveal conserved stress-responsive molecules relevant to brain pathology. Shared gene signatures between PD and inflammatory bowel disease (IBD) were identified from peripheral blood transcriptomes using weighted gene co-expression network analysis (WGCNA). Hub genes were prioritized via protein–protein interaction (PPI) analysis and evaluated for expression consistency in independent brain tissue transcriptomic datasets. Single-cell RNA sequencing (scRNA-seq) of the PD substantia nigra was used to define the cellular context of the key hub gene, and CellChat analysis assessed intercellular communication changes. Immunofluorescence validation was performed in an MPTP-induced PD mouse model. We identified 79 shared genes and 6 hub genes, among which only HSP90AA1 showed consistent upregulation across independent PD transcriptomic validation datasets. Functional enrichment highlighted inflammation-related pathways. Because peripheral immune infiltration showed only minor changes, we further investigated the cellular context of HSP90AA1 within the PD brain. ScRNA-seq analysis of the PD substantia nigra demonstrated that HSP90AA1 was expressed across multiple cell populations. Integration with transcriptional regulatory analysis identified TP53 as a potential upstream regulator, and the strongest TP53–HSP90AA1 co-expression and cellular colocalization signals were observed in astrocytes, prompting further astrocyte-focused investigation. CellChat analysis revealed altered intercellular communication patterns in PD substantia nigra, including changes in synapse-associated ligand–receptor interaction signatures, particularly involving NCAM-related pathways. In the MPTP-induced PD mouse model, immunofluorescence identified astrocytic HSP90α upregulation, and increased nuclear p53 signal in astrocytes, accompanied by dopaminergic neuron loss. Conclusion: Astrocytic upregulation of HSP90AA1 is associated with altered synapse-related intercellular communication patterns in the PD substantia nigra, potentially involving a predicted TP53 associated regulatory component. These findings, validated in an MPTP mouse model, identify HSP90AA1 as a candidate stress-responsive hub linking peripheral inflammatory states with astrocyte-associated molecular alterations in PD, providing a framework for further experimental investigation. Full article

Background/Objectives: Gastrointestinal dysmotility (GID) is a frequent non-motor manifestation of Parkinson’s disease (PD). However, its peripheral electrophysiological characteristics, as well as the underlying neural mechanisms within the brain–gut axis, remain insufficiently understood. This study aimed to delineate spatiotemporal abnormalities in gastrointestinal pacing activity in PD and to explore their associations with cerebral functional connectivity (FC). Methods: Multichannel electrogastroenterography (EGEG) recordings, including both preprandial and postprandial states from gastric (leads 1–4) and intestinal (leads 5–8) regions, were obtained from patients with PD and healthy controls (HCs), alongside resting-state functional MRI (rs-fMRI). The striatal–thalamic circuit was selected as the seed region for FC analysis. Between-group differences in EGEG-derived spatiotemporal metrics were assessed using analysis of covariance (ANCOVA), while FC differences were examined using two-sample t-tests. Partial correlation analyses were conducted to evaluate associations among neuroimaging measures, aberrant gastrointestinal electrophysiological indices, and clinical variables. Regional specificity of correlations was further tested by comparing dependent correlation coefficients. In addition, multivariate brain–gut connectivity was assessed using partial canonical correlation analysis (pCCA) with 1000 permutation tests. Results: Relative to HCs, PD patients exhibited a significant reduction in the proportion of normal slow waves in both gastric and intestinal regions during preprandial and postprandial states (pFDR < 0.05). FC analysis revealed increased connectivity between the left thalamus and right insula in PD, whereas interhemispheric connectivity of the caudate nuclei and putamina was significantly reduced. Additionally, FC between the left pallidum and left precentral gyrus was attenuated in the PD group. Partial correlation analysis demonstrated a positive association between postprandial normal slow-wave fraction and interhemispheric caudate connectivity (r = 0.63, pFDR = 0.047). Furthermore, left thalamus–right insula connectivity correlated with both total Non-Motor Symptoms Scale (NMSS) scores (r = 0.57, pFDR = 0.042) and gastrointestinal subscale scores (r = 0.63, pFDR = 0.037). At the multivariate level, pCCA revealed a strong association between lentiform nucleus connectivity and preprandial gastric slow-wave rhythms (canonical r = 0.892, p = 0.004). Conclusions: In PD, caudate nucleus FC shows a preferential association with gastric rather than intestinal electrophysiological activity. Multivariate analyses further demonstrate a significant network-level association between lentiform nucleus connectivity and baseline gastric pacing rhythms, extending regional findings to a broader network interaction. Together, these results provide multimodal correlational evidence reflecting parallel central and peripheral alterations in PD, highlighting synchronized alterations in central networks and peripheral gastrointestinal rhythmicity. Full article

Dietary patterns increasingly influence research on neurodegenerative diseases, with attention shifting from isolated nutrients to integrative nutritional models. The Amazonian Diet, a biodiversity-based dietary pattern rich in native fruits, seeds, freshwater fish, and cassava-derived foods, is naturally enriched in bioactive compounds including polyphenols, anthocyanins, carotenoids, methylxanthines, selenium, vitamins, and unsaturated fatty acids. This review aimed to investigate the potential relevance of key foods derived from the Amazonian Diet to Parkinson’s disease (PD) by integrating compositional nutritional analysis, multivariate analytical approaches, and mechanistic evidence synthesis. In Stage 1, the composition of 36 Amazonian foods was analyzed using TBCA and FAO data, followed by hierarchical clustering analysis (Ward’s linkage, Euclidean distance). Distinct compositional patterns were identified, highlighting foods with high bioactive diversity, relevant lipid composition, and dietary fiber. In Stage 2, an integrative literature review (PubMed/MEDLINE, SciELO) of in vitro, in vivo, observational, and clinical studies suggested that açaí berry, guaraná, cocoa/cacao, camu-camu, and Brazil nuts contain nutrients and bioactive compounds that intersect with biological pathways implicated in PD, including oxidative stress, mitochondrial dysfunction, and neuroinflammation. However, this review does not evaluate the effects of the Amazonian Diet on PD incidence, progression, symptoms, levodopa response, or biomarkers. Full article

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder with a well- documented prodromal phase during which non-motor symptoms appear years before motor onset. Seborrheic dermatitis (SD) is a chronic inflammatory skin disease that is significantly more prevalent in PD patients than in the general population. The biological mechanisms underlying this association have not been integrated into a single framework. Objectives: This narrative review aims to synthesise the available evidence on the molecular, genetic, and pathophysiological mechanisms linking SD and PD. Methods: A literature search was conducted across PubMed/MEDLINE, Scopus and ScienceDirect, supplemented by manual searches in OMIM and GeneCards. Results: Four major biological links between SD and PD have been proposed. First, alpha-synuclein deposits are detectable in cutaneous nerve fibres and autonomic fibres innervating sebaceous glands in PD patients and their pattern has been associated with disease subtype and progression. Second, dysfunction in ceramide and sphingolipid metabolism, associated with variants in GBA1, LRRK2, and ZNF750, has been linked to impaired lysosomal function and skin barrier integrity in both brain and skin tissue. Third, Malassezia, a commonly associated organism and possible trigger in susceptible hosts, produces metabolites that activate neuroinflammatory pathways relevant to PD and PD patients show altered Malassezia species composition on their skin. Fourth, NLRP3 inflammasome activation, which can be triggered by ceramide accumulation and fungal metabolites, has been proposed as a shared inflammatory mechanism that may operate in both keratinocytes and dopaminergic neurons. Conclusions: SD and PD appear to share overlapping genetic, lipidomic, microbial, and neuroinflammatory features. These associations are consistent with, but do not yet prove, a common pathological basis rather than a coincidental one. SD may therefore represent a potential prodromal feature or risk marker of PD. Future research should examine whether targeted intervention in high-risk SD patients can delay or modify PD onset. Full article