Movement Disorders最新文献

{"title":"Video-Based Data-Driven Models for Diagnosing Movement Disorders: Review and Future Directions.","authors":"Rafael Martínez-García-Peña,Lisette H Koens,George Azzopardi,Marina A J Tijssen","doi":"10.1002/mds.30327","DOIUrl":"https://doi.org/10.1002/mds.30327","url":null,"abstract":"Movement disorders are abnormal, involuntary movements that can heavily impact a person's quality of life. In clinical practice, diagnosis and severity assessments rely mainly on visual clinical inspections (ie, on subjective expert opinion). With clinical videos commonly acquired as part of examinations, novel data-driven models have emerged that use machine learning (ML) and deep learning (DL) algorithms to capture human actions and recognize their characteristics, showing promise as new tools in clinical workflows. This review seeks to provide a comprehensive examination of video-based, data-driven models for movement disorders, including tremor, dystonia, myoclonus, chorea, tics, Parkinson's disease, and ataxia. We explore literature from 2006 to 2024 in a variety of scientific databases, with different video modalities including red-green-blue video of different frame rates, depth video, marker-based approaches, multi-perspective approaches, and multimodal video. We discover a significant trend in studies favoring pose estimation methods, with newer studies incorporating real-time methods and end-to-end DL architectures, and usability is steadily increasing and rapidly approaching expert-level performance. Likewise, we present the main limitations in the current approaches, such as limited public sources of data, lack of standardized metrics, and patient privacy. Taking inspiration from other fields, in medicine and otherwise, we propose possible future research directions including explainable artificial intelligence techniques, privacy-preserving devices and modeling techniques, and better metric guidelines. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"15 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Waveform-Based Analysis of Head Tremor Using a Marker-Less Tracking Algorithm with 2D-Video: Evaluation of Sinusoidality and Rhythmicity.","authors":"Jung Hwan Shin,Seungmin Lee,Kyung Ah Woo,Hyder A Jinnah,Aasef Shaikh,Mark Hallett,Sanjay Pandey,Rick C Helmich,Marie Vidailhet,Victor Fung,Alfonso Fasano,Han-Joon Kim,Beomseok Jeon","doi":"10.1002/mds.30322","DOIUrl":"https://doi.org/10.1002/mds.30322","url":null,"abstract":"BACKGROUND AND OBJECTIVETremor is defined as involuntary, rhythmic, and sinusoidal movements. However, differentiating different types of tremors remains challenging due to overlapping features and the subjective nature of clinical evaluations. This study aimed to introduce a novel, video-based waveform analysis to objectively measure two fundamental tremor characteristics, rhythmicity and sinusoidality.METHODSBased on waveforms derived from video-based analysis tracking the patients' nose tip, we defined the coefficient of variation of interpeak intervals (CVIPI) as the measure of rhythmicity index and the slope-fold ratio as the sinusoidality index. For convergent validation, we prospectively enrolled 13 cervical dystonia (CD) patients with head tremor and simultaneously recorded tremor data using both video-based and gyroscope-based methods. Additionally, we applied the algorithm to archived videos of 28 CD and 22 essential tremor (ET) cases with head tremor to analyze individual and group tremor characteristics.RESULTSVideo-based indices demonstrated excellent agreement with gyroscope-based measurements for peak frequency (intraclass correlation coefficient [ICC] = 0.99) and the sinusoidality index (ICC = 0.93), while the rhythmicity index showed good reliability (ICC = 0.86). In the application study, CD cases showed significantly lower rhythmicity and sinusoidality than ET cases, forming distinct data-driven clusters between CD and ET. The accuracy of these clusters to the clinical diagnosis was 82.1% and 63.6% for CD and ET, respectively.CONCLUSIONSVideo-based analysis of tremor waveforms offers an objective evaluation of rhythmicity and sinusoidality, providing a tool for the objective description of tremor syndromes. Distinct yet overlapping waveform features in ET and CD, analyzed with video analysis, highlight the variability of tremor syndromes. © 2025 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Metabolomics Profiles in Prodromal and Clinical Parkinson's Disease.","authors":"Mario H Flores-Torres,Xiaojing Peng,Sarah Jeanfavre,Clary Clish,Ying Wang,Marjorie L McCullough,Brian Healy,Michael A Schwarzschild,Kjetil Bjornevik,Alberto Ascherio","doi":"10.1002/mds.30308","DOIUrl":"https://doi.org/10.1002/mds.30308","url":null,"abstract":"BACKGROUNDThe long prodromal phase of Parkinson's disease (PD) and the link the disease has with metabolic factors suggest that metabolomics could help identify affected individuals at early stages.OBJECTIVEThe goal was to examine whether plasma metabolomic profiles could identify individuals in the prodromal and clinical phase of PD.METHODSWe quantified and compared the plasma metabolomic profiles of 922 individuals with PD who provided blood samples at a median of 11 years before (n = 809) or 2 years after (n = 113) disease diagnosis to that of matched controls, all selected from three established cohort studies (Nurses' Health Study, Health Professionals Follow-up Study, and Cancer Prevention Study II). We used conditional logistic regression models and machine learning techniques to identify metabolites predicting prodromal and clinically manifest PD.RESULTSSeveral metabolites, especially amino acids, acyl-carnitines, and other lipids were nominally associated with PD since the years leading to disease diagnosis. Metabolites proposed as biomarkers of foods or care products tended to be associated with a higher PD risk closer to disease diagnosis. Metabolites reflecting higher intake of coffee, smoking, and acetaminophen tended to be associated with a lower PD risk over the course of the disease. Metabolomic profiles in prodromal samples were unable to accurately predict future clinical PD.CONCLUSIONSMetabolic pathways related to the metabolism of amino acids and lipids may be involved in PD progression. Metabolomic differences may also result from behavioral changes and medical management, emphasizing the need to consider prodromal and clinical data in future studies. © 2025 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"37 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Dysfunction of the Amygdala and Nucleus Basalis Underlies Visual Hallucinations in Parkinson's Disease.","authors":"Anna Ignatavicius,Lachlan Churchill,Jack Anderson,Ajay Konuri,Claire O'Callaghan,Simon J G Lewis,Elie Matar","doi":"10.1002/mds.70011","DOIUrl":"https://doi.org/10.1002/mds.70011","url":null,"abstract":"BACKGROUNDVisual hallucinations (VHs) are a common feature of Parkinson's disease (PD) believed to arise from disruptions to the functional architecture supporting sensory integration and attentional control. Across synucleinopathies, increased pathological burden in the amygdala and deficits in cholinergic modulation have been linked to VHs. However, the interaction of these changes and their combined contribution to the neurobiological mechanisms underlying hallucinatory phenomena remain poorly understood.OBJECTIVESTo investigate the convergent impact of amygdala and cholinergic dysfunction on VHs in PD.METHODSSeventy patients with PD, including 30 with and 40 without VHs, underwent structural and resting-state functional magnetic resonance imaging. Seed-based analyses were performed to examine whether altered functional connectivity between the bilateral amygdala and the cholinergic nucleus basalis of Meynert (NBM) with cortical networks involved in attention and visual processing is related to the presence of VHs.RESULTSPatients with VHs exhibited reduced amygdala connectivity with the visual network and reduced left amygdala connectivity with both dorsal and ventral attentional networks compared with those without VHs. Furthermore, mediation analyses indicated that the association between amygdala-attentional network dysconnectivity and VHs was at least partially explained by functional interactions between the left NBM and the ventral attention network. These functional alterations were not associated with amygdala or NBM volumes, suggesting they may occur independently of measurable gray matter atrophy.CONCLUSIONSOur findings demonstrate that VHs are associated with a network signature of impaired functional connectivity linking the amygdala, cholinergic dysfunction, and cortical networks associated with attention and perception. These results highlight the interplay between distinct but related neural circuitries and provide new insights into the pathophysiological mechanisms of VHs in PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"20 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive Phenotyping of Parkinson's Disease Patients Via Digital Analysis of Spoken Word Properties.","authors":"Franco J Ferrante,Daniel Escobar Grisales,María Fernanda López,Pamela Lopes da Cunha,Lucas Federico Sterpin,Jet M J Vonk,Pedro Chaná Cuevas,Claudio Estienne,Eugenia Hesse,Lucía Amoruso,Juan Rafael Orozco Arroyave,Adolfo M García","doi":"10.1002/mds.70005","DOIUrl":"https://doi.org/10.1002/mds.70005","url":null,"abstract":"BACKGROUNDCognitive symptoms are highly prevalent in Parkinson's disease (PD), often manifesting as mild cognitive impairment (MCI). Yet, their detection and characterization remain suboptimal because standard approaches rely on subjective impressions derived from lengthy, univariate tests.OBJECTIVEWe examined whether digital analysis of verbal fluency predicts cognitive status in PD.METHODSWe asked 464 Spanish speakers with PD to complete taxonomic (animal), thematic (supermarket), and phonemic (/p/) fluency tasks. We quantified six response properties: semantic variability, granularity, concreteness, length, frequency, and phonological neighborhood. In Study 1, these properties were fed to a ridge regressor to predict Mattis Dementia Rating Scale (MDRS) scores and subscores. In Study 2, we used the same properties to compare (via a generalized linear model) and classify (via random forest) between 123 patients with and 124 without MCI.RESULTSIn Study 1, predicted MDRS scores and subscores strongly correlated with actual ones, adjusting for clinical and cognitive variables (R = 0.51, P < 0.001). In Study 2, MCI patients' words were less semantically variable, less concrete, and shorter, adjusting for clinical and cognitive variables (P-values < 0.05). Machine learning discrimination between patients with and without MCI was robust in the validation set (area under the curve [AUC] = 0.76), with good generalization to unseen pre-surgical (AUC = 0.68) and post-surgical (AUC = 0.72) samples, surpassing MDRS scores (AUC = 0.54). Results were consistently driven by semantic variability, granularity, and concreteness.CONCLUSIONSDigital word property analysis predicts cognitive symptom severity and distinguishes between cognitive phenotypes of PD, enabling scalable neuropsychological screenings. © 2025 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"6 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Neuroinflammatory and Anti-Inflammatory Effects of the NLRP3 Inhibitor NT-0796 in Subjects with Parkinson's Disease.","authors":"Nicholas Clarke,Peter Thornton,Valérie Reader,Nicola Lindsay,Zsofia Digby,Bianca Mullen,Michelle Gorman,Eric Jacobson,Grant Langdon,Hilary Johnstone,Alistair Wheeler,Alan P Watt","doi":"10.1002/mds.30307","DOIUrl":"https://doi.org/10.1002/mds.30307","url":null,"abstract":"BACKGROUNDInhibition of Nod-like receptor protein 3 (NLRP3) inflammasome within the central nervous system (CNS) is a promising therapeutic target for the treatment of Parkinson's disease (PD).OBJECTIVESThis phase 1b open-label study was conducted in elderly healthy volunteers (HV) and PD patients. The study was designed to assess safety and tolerability and to evaluate the central and systemic pharmacokinetic profile and anti-inflammatory effects of a total daily dose of 300 mg NT-0796 (oral 150 mg suspension capsule formulation every 12 h).METHODSFour elderly HV and 10 subjects with PD received 150 mg open-label NT-0796 every 12 h for either 7 or 28 days, respectively. Blood and cerebrospinal fluid (CSF) were collected via serial sampling or lumbar punctures for pharmacokinetic and biomarker analyses. Standard safety parameters were monitored throughout.RESULTSNT-0796 was safe and well tolerated with minimal adverse events. A reduced peak-to-trough ratio along with moderately higher exposure than the solution formulation (used in the first-in-human study) was observed, along with significant CSF exposure in elderly HV and subjects with PD. NT-0796 drove reductions in systemic inflammatory markers including high-sensitivity C-reactive protein, fibrinogen, interleukin (IL)-6, and IL-18. Furthermore, reductions in neuroinflammation, including IL-1β, were indicative of NT-0796's target engagement within the central nervous system (CNS) of subjects with PD.CONCLUSIONSCNS inhibition of NLRP3 with NT-0796 reduced neuroinflammation over a sustained 28-day dosing period and demonstrates the potential for long-term dosing of NT-0796 in future studies of patients with neurodegeneration. © 2025 NodThera Limited. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"53 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probabilistic Mapping of Magnetic Resonance-Guided Focused Ultrasound (MRgFUS) Thalamotomy Targets in Essential Tremor and Tremor-Dominant Parkinson's Disease: Insights from a German Cohort.","authors":"Jonas Krauss,Neeraj Upadhyay,Veronika Purrer,Valeri Borger,Marcel Daamen,Hannah Weiland,Angelika Maurer,Carsten Schmeel,Alexander Radbruch,Markus Essler,Ullrich Wüllner,Henning Boecker","doi":"10.1002/mds.70003","DOIUrl":"https://doi.org/10.1002/mds.70003","url":null,"abstract":"Precise targeting in magnetic resonance-guided focused ultrasound (MRgFUS) is critical for effective tremor control in essential tremor and tremor-dominant Parkinson's disease, as small deviations can reduce efficacy or cause side effects. In our cohort, sweetspots were identified at Montreal Neurological Institute (MNI) coordinates x = -12.4, y = -17.5, z = -1.7 (ET) and x = -13.4, y = -19.8, z = -3.0 (TDPD).","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"95 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on Schwarz et al. “EFNB3 Frameshift Variant in Weimaraner Dogs with a Condition Resembling a Congenital Mirror Movement Disorder”","authors":"Oriane Trouillard PhD,&nbsp;Quentin Welniarz PhD,&nbsp;Aurélie Méneret MD, PhD,&nbsp;Caroline Dubacq PhD,&nbsp;Emmanuel Roze MD, PhD","doi":"10.1002/mds.70001","DOIUrl":"10.1002/mds.70001","url":null,"abstract":"&lt;p&gt;We read with great interest the recent publication reporting the study of Weimaraner dog siblings with a hopping gait,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; that is, a loss of the left–right alternation of limb movements during locomotion. This phenotype was caused by a homozygous pathogenic variant in &lt;i&gt;EFNB3&lt;/i&gt; encoding ephrin B3. In humans, lack of motor control lateralization results in mirror movements (MM). Therefore, the authors suggested that &lt;i&gt;EFNB3&lt;/i&gt; could be a new candidate gene in patients with congenital mirror movements (CMM). To investigate a potential role of &lt;i&gt;EFNB3&lt;/i&gt;, we analyzed exome sequencing data from 59 CMM index cases with no pathogenic variant in the known CMM causative genes. We did not identify any variants in the &lt;i&gt;EFNB3&lt;/i&gt; gene. Thus, this gene does not appear to be involved in CMM.&lt;/p&gt;&lt;p&gt;This finding is not unexpected because a hopping gait is not equivalent to MM.&lt;sup&gt;2&lt;/sup&gt; The hopping gait results from a dysfunction of the central pattern generators within the spinal cord. MMs are rather related to anatomical and functional abnormalities of supra-spinal structures, such as abnormal bilateral corticospinal tract (CST) projections to the spinal cord and/or abnormal interhemispheric interactions.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Several lines of evidence support this hypothesis. In mice, a hopping gait was associated with mutations in &lt;i&gt;Dcc&lt;/i&gt;, the gene encoding a netrin-1 receptor&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; and &lt;i&gt;Epha4&lt;/i&gt;, the gene encoding the ephrin-B3 receptor.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Both genes are involved in the guidance at the midline of the CST and commissural spinal neurons. In knock-out mice for &lt;i&gt;Dcc&lt;/i&gt; or &lt;i&gt;Epha4&lt;/i&gt;, both the CST and spinal circuitry are affected. It is thus difficult to disentangle the respective contribution of these structures to the hopping gait.&lt;span&gt;&lt;sup&gt;3, 4&lt;/sup&gt;&lt;/span&gt; Strikingly, conditional deletion of any of these two genes restricted to the spinal cord is sufficient to produce a hopping gait.&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt; Their respective deletion in the CST does not alter stereotypic locomotion.&lt;span&gt;&lt;sup&gt;3, 4&lt;/sup&gt;&lt;/span&gt; In particular, deletion of Epha4 within the neocortex results in aberrant bilateral CST projections to the spinal cord while the spinal circuitry is unaffected. These mutants have a normal stereotypic locomotion.&lt;span&gt;&lt;sup&gt;4, 6&lt;/sup&gt;&lt;/span&gt; By contrast, they have abnormal bilateral reaching behavior and a hopping gait specifically during adaptive locomotion that requires supra-spinal control,&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; a phenotype that reflects human MM. Last, mutations of the &lt;i&gt;Dmrt3&lt;/i&gt; gene, encoding a transcription factor involved in the development of commissural spinal interneurons, are associated with the ability to produce alternated gait in horses.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; &lt;i&gt;Dmrt3&lt;/i&gt; mutations are present in horse breeds that are able to produce alternated gait at intermediate speeds, without transition to gallop, in which limb movements are symm","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 9","pages":"2023-2024"},"PeriodicalIF":7.6,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://movementdisorders.onlinelibrary.wiley.com/doi/epdf/10.1002/mds.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144792147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: “EFNB3 Frameshift Variant in Weimaraner Dogs with a Condition Resembling a Congenital Mirror Movement Disorder”","authors":"Cleo Schwarz DVM,&nbsp;Florian Bartenschlager DVM, PhD, DECVP,&nbsp;Olivia Kershaw DVM, DECVP,&nbsp;Judith Braun DVM,&nbsp;Julien Guevar DVM, MVM, DECVN, MRCVS,&nbsp;Vidhya Jagannathan PhD,&nbsp;Jörg T. Epplen MD,&nbsp;Wencke Reineking DVM,&nbsp;Wolfgang Baumgärtner DVM, PhD, DECVP, DACVP (Hon.),&nbsp;Kailash P. Bhatia MD, FRCP,&nbsp;Achim D. Gruber DVM, PhD, DECVP,&nbsp;Tosso Leeb PhD","doi":"10.1002/mds.70000","DOIUrl":"10.1002/mds.70000","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 9","pages":"2025-2026"},"PeriodicalIF":7.6,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired Glymphatic Clearance, Measured Using Diffusion Tensor Image Analysis Along the Perivascular Space (DTI-ALPS), is Linked to Poor Cognitive Outcomes in Parkinson's Disease.","authors":"Angeliki Zarkali,George Thomas,Ross Paterson,Naomi Hannaway,Ivelina Dobreva,Amanda J Heslegrave,Elena Veleva,Henrik Zetterberg,Rimona S Weil","doi":"10.1002/mds.30325","DOIUrl":"https://doi.org/10.1002/mds.30325","url":null,"abstract":"BACKGROUNDImpaired glymphatic clearance may contribute to pathological accumulations in Parkinson's (PD), but how it interacts with other processes causing dementia remains unclear. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) has been proposed as an indirect proxy for glymphatic clearance.OBJECTIVESTo clarify DTI-ALPS' relationship with cognition in PD, and its relationship with established imaging markers.METHODSWe assessed DTI-ALPS in 98 PD patients (31 PD poor outcomes: dementia, mild cognitive impairment, frailty, or death within a 3-year follow-up; 67 PD good outcomes) and 28 controls. We assessed DTI-ALPS' relationship to cognition, white matter (fiber cross-section), cortical thickness, iron accumulation (quantitative susceptibility mapping [QSM]), and plasma markers [phosphorylated tau-181 (p-tau181 and neurofilament light (NfL)] cross-sectionally and longitudinally).RESULTSDTI-ALPS was lower in PD-poor outcomes compared with PD good outcomes and controls (P = 0.005) with further longitudinal reductions only in PD poor outcomes (group × time interaction: β = -0.013, P = 0.021). Lower DTI-ALPS was associated with lower fiber cross-section in PD, at baseline and longitudinally but with different spatial distribution from white matter changes relating to PD cognition. There was no correlation between baseline DTI-ALPS and plasma p-tau181 (P = 0.642), NFL (P = 0.448), or baseline cortical thickness. Lower DTI-ALPS was associated with accelerated cortical thinning within left precentral gyrus and changes in brain iron distribution.CONCLUSIONSPD patients who develop poor outcomes show lower DTI-ALPS, potentially reflecting impaired glymphatic clearance. DTI-ALPS correlated with white matter integrity and brain iron accumulation. However, both showed different spatial distribution than that seen in PD dementia, suggesting DTI-ALPS captures a distinct contribution to cognitive decline. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"32 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}