NPJ Parkinson's Disease最新文献

{"title":"A systematic exploration of unexploited genes for oxidative stress in Parkinson's disease.","authors":"Takayuki Suzuki, Hidemasa Bono","doi":"10.1038/s41531-024-00776-1","DOIUrl":"10.1038/s41531-024-00776-1","url":null,"abstract":"<p><p>Human disease-associated gene data are accessible through databases, including the Open Targets Platform, DisGeNET, miRTex, RNADisease, and PubChem. However, missing data entries in such databases are anticipated because of curational errors, biases, and text-mining failures. Additionally, the extensive research on human diseases has led to challenges in registering comprehensive data. The lack of essential data in databases hinders knowledge sharing and should be addressed. Therefore, we propose an analysis pipeline to explore missing entries of unexploited genes in the human disease-associated gene databases. Using this pipeline for genes in Parkinson's disease with oxidative stress revealed two unexploited genes: nuclear protein 1 (NUPR1) and ubiquitin-like with PHD and ring finger domains 2 (UHRF2). This methodology enhances the identification of underrepresented disease-associated genes, facilitating easier access to potential human disease-related functional genes. This study aims to identify unexploited genes for further research and does not include independent experimental validation.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"10 1","pages":"160"},"PeriodicalIF":6.7,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996292","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":"MRI subtypes in Parkinson’s disease across diverse populations and clustering approaches","authors":"Anna Inguanzo, Rosaleena Mohanty, Konstantinos Poulakis, Daniel Ferreira, Barbara Segura, Franziska Albrecht, J-Sebastian Muehlboeck, Tobias Granberg, Henrik Sjöström, Per Svenningsson, Erika Franzén, Carme Junqué, Eric Westman","doi":"10.1038/s41531-024-00759-2","DOIUrl":"https://doi.org/10.1038/s41531-024-00759-2","url":null,"abstract":"<p>Parkinson’s disease (PD) is clinically heterogeneous, which suggests the existence of subtypes; however, there has been no consensus regarding their characteristics. This study included 633 PD individuals across distinct cohorts: unmedicated de novo PD, medicated PD, mild-moderate PD, and a cohort based on diagnostic work-up in clinical practice. Additionally, 233 controls were included. Clustering based on cortical and subcortical gray matter measures was conducted with and without adjusting for global atrophy in the entire PD sample and validated within each cohort. Subtypes were characterized using baseline and longitudinal demographic and clinical data. Unadjusted results identified three clusters showing a gradient of neurodegeneration and symptom severity across the entire sample and the individual cohorts. When adjusting for global atrophy eight clusters were identified in the entire sample, lacking consistency in individual cohorts. This study identified atrophy-based subtypes in PD, emphasizing the significant impact of global atrophy on subtype number, patterns, and interpretation in cross-sectional analyses.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"8 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992007","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":"Risk willingness in multiple system atrophy and Parkinson’s disease understanding patient preferences","authors":"Alexander Maximilian Bernhardt, Marc Oeller, Isabel Friedrich, Emre Kocakavuk, Eliana Nachman, Kevin Peikert, Malte Roderigo, Andreas Rossmann, Tabea Schröter, Lea Olivia Wilhelm, Tino Prell, Christoph van Riesen, Johanna Nieweler, Sabrina Katzdobler, Markus Weiler, Heike Jacobi, Tobias Warnecke, Inga Claus, Carla Palleis, Stephan Breimann, Björn Falkenburger, Moritz Brandt, Andreas Hermann, Jost-Julian Rumpf, Joseph Claßen, Günter Höglinger, Florin Gandor, Johannes Levin, Armin Giese, Annette Janzen, Wolfgang Hermann Oertel","doi":"10.1038/s41531-024-00764-5","DOIUrl":"https://doi.org/10.1038/s41531-024-00764-5","url":null,"abstract":"<p>Disease-modifying therapeutics in the α-synucleinopathies multiple system atrophy (MSA) and Parkinson’s Disease (PD) are in early phases of clinical testing. Involving patients’ preferences including therapy-associated risk willingness in initial stages of therapy development has been increasingly pursued in regulatory approval processes. In our study with 49 MSA and 38 PD patients, therapy-associated risk willingness was quantified using validated standard gamble scenarios for varying severities of potential drug or surgical side effects. Demonstrating a non-gaussian distribution, risk willingness varied markedly within, and between groups. MSA patients accepted a median 1% risk [interquartile range: 0.001–25%] of sudden death for a 99% [interquartile range: 99.999–75%] chance of cure, while PD patients reported a median 0.055% risk [interquartile range: 0.001–5%]. Contrary to our hypothesis, a considerable proportion of MSA patients, despite their substantially impaired quality of life, were not willing to accept increased therapy-associated risks. Satisfaction with life situation, emotional, and nonmotor disease burden were associated with MSA patients’ risk willingness in contrast to PD patients, for whom age, and disease duration were associated factors. An individual approach towards MSA and PD patients is crucial as direct inference from disease (stage) to therapy-associated risk willingness is not feasible. Such studies may be considered by regulatory agencies in their approval processes assisting with the weighting of safety aspects in a patient-centric manner. A systematic quantitative assessment of patients’ risk willingness and associated features may assist physicians in conducting individual consultations with patients who have MSA or PD by facilitating communication of risks and benefits of a treatment option.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"25 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986361","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":"CSF markers of neurodegeneration Alzheimer’s and Lewy body pathology in isolated REM sleep behavior disorder","authors":"Amaia Muñoz-Lopetegi, Simone Baiardi, Mircea Balasa, Angela Mammana, Gerard Mayà, Marcello Rossi, Mónica Serradell, Corrado Zenesini, Alice Ticca, Joan Santamaria, Sofia Dellavalle, Carles Gaig, Alex Iranzo, Piero Parchi","doi":"10.1038/s41531-024-00770-7","DOIUrl":"https://doi.org/10.1038/s41531-024-00770-7","url":null,"abstract":"<p>We investigated the biomarker profile of neurodegeneration, Alzheimer’s and Lewy body pathology in the CSF of 148 polysomnography-confirmed patients with isolated REM sleep behavior disorder (IRBD), a condition that precedes Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). We assessed misfolded α-synuclein (AS) by RT-QuIC assay, amyloid-beta peptides (Aβ₄₂ and Aβ₄₀), phosphorylated tau (p-tau), and total tau (t-tau) by CLEIA and neurofilament light chain (NfL) by ELISA. We detected AS in 75.3% of patients, pathologically decreased Aβ₄₂/Aβ₄₀ ratio in 22.5%, increased p-tau in 15.5%, increased t-tau in 14.9%, and elevated NfL in 14.7%. After a mean follow-up of 2.48 ± 2.75 years, 47 (38.1%) patients developed PD (<i>n</i> = 24) or DLB (<i>n</i> = 23). At CSF collection, AS positivity [HR 4.05 (1.26–12.99), <i>p</i> = 0.019], mild cognitive impairment [3.86 (1.96–7.61), <i>p</i> &lt; 0.001], and abnormal DAT-SPECT [2.31 (1.09–4.91), <i>p</i> &lt; 0.030] were independent predictors of conversion to PD and DLB. Among the other CSF markers, only elevated p-tau/Aβ₄₂ was predictive of conversion, although only to DLB and not as an independent variable. In IRBD, CSF AS assessment by RT-QuIC provides an added value in defining the risk of short-term conversion to PD and DLB independent of clinical and instrumental investigations. Positive Alzheimer's disease (AD) pathology markers and elevated NfL occur in a subgroup of patients, but p-tau/Aβ₄₂ is the only marker that predicts short-term conversion to DLB. Longer follow-up is needed to assess if AD biomarkers predict the later development of PD and DLB in IRBD.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"32 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986290","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":"Loss-of-function variants in ITSN1 confer high risk of Parkinson’s disease","authors":"Astros Th. Skuladottir, Vinicius Tragante, Gardar Sveinbjornsson, Hannes Helgason, Arni Sturluson, Anna Bjornsdottir, Palmi Jonsson, Vala Palmadottir, Olafur A. Sveinsson, Brynjar O. Jensson, Sigurjon A. Gudjonsson, Erna V. Ivarsdottir, Rosa S. Gisladottir, Arni F. Gunnarsson, G. Bragi Walters, Gudrun A. Jonsdottir, Thorgeir E. Thorgeirsson, Gyda Bjornsdottir, Hilma Holm, Daniel F. Gudbjartsson, Patrick Sulem, Hreinn Stefansson, Kari Stefansson","doi":"10.1038/s41531-024-00752-9","DOIUrl":"https://doi.org/10.1038/s41531-024-00752-9","url":null,"abstract":"<p>Parkinson’s disease (PD) is a debilitating neurodegenerative disorder and its rising global incidence highlights the need for the identification of modifiable risk factors. In a gene-based burden test of rare variants (8647 PD cases and 777,693 controls) we discovered a novel association between loss-of-function variants in <i>ITSN1</i> and PD. This association was further supported with burden data from the Neurodegenerative Disease Knowledge Portal and the Accelerating Medicines Partnership Parkinson’s Disease Knowledge Platform. Our findings show that Rho GTPases and disruptions in synaptic vesicle transport may be involved in the pathogenesis of PD, pointing to the possibility of novel therapeutic approaches.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"13 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986359","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":"Diagnostic accuracy and predictors of alpha-synuclein accumulation in the gastrointestinal tract of Parkinson’s disease","authors":"Chaewon Shin, Seong-Ik Kim, Sung-Hye Park, Jong-Min Kim, Jee-Young Lee, Sun Ju Chung, Jae Woo Kim, Tae-Beom Ahn, Kye Won Park, Jung Hwan Shin, Chan Young Lee, Hyuk-Joon Lee, Seong-Ho Kong, Yun-Suhk Suh, Han-Joon Kim, Han-Kwang Yang, Beomseok Jeon","doi":"10.1038/s41531-024-00766-3","DOIUrl":"https://doi.org/10.1038/s41531-024-00766-3","url":null,"abstract":"<p>The only characteristic of alpha-synuclein (AS) accumulation in the gastrointestinal (GI) tract of Parkinson’s disease (PD) found in pathological studies is the “rostrocaudal gradient,” which describes the more frequent presence of AS accumulation in the upper GI tract than in the lower GI tract. This study aimed to determine the diagnostic accuracy and identify predictors of AS accumulation in the GI tract of PD patients. The frequency of AS accumulation in the GI tract was compared between PD patients (<i>N</i> = 97) who underwent radical GI surgery for cancer and individually matched controls (<i>N</i> = 94). We evaluated AS accumulation in the neural structures using phosphorylated AS immunohistochemistry. A multivariable logistic regression analysis was conducted to determine the predictors of AS accumulation in the GI tract of PD patients. The frequency of AS accumulation was significantly higher in PD patients (75.3%) than in controls (8.5%, <i>p</i>-value &lt; 0.001). The sensitivity and specificity of the full-layer evaluation were 75.3% and 91.5%, respectively. When the evaluation was confined to the mucosal/submucosal layer, the sensitivity and specificity were 46.9% and 94.7%, respectively. The rostrocaudal gradient of AS accumulation was found in PD patients. The duration from symptom onset to surgery was significantly longer in PD patients with AS accumulation (4.9 ± 4.9 years) than in PD patients without AS accumulation (1.8 ± 4.1 years, <i>p</i>-value = 0.005). Both disease duration and rostrocaudal gradient independently predicted the presence of AS accumulation in the GI tract of PD patients. Our study suggests PD-related AS accumulation in the GI tract follows a temporally increasing but spatially static progression pattern.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"379 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986362","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":"rTMS improves dysphagia by inhibiting NLRP3 inflammasome activation and caspase-1 dependent pyroptosis in PD mice","authors":"Peiling Huang, Ziman Zhu, Wenshan Li, Rong Zhang, Yijia Chi, Weijun Gong","doi":"10.1038/s41531-024-00775-2","DOIUrl":"https://doi.org/10.1038/s41531-024-00775-2","url":null,"abstract":"<p>High incidence, severe consequences, unclear mechanism, and poor treatment effect happened in Parkinson’s disease-related dysphagia. Repetitive transcranial magnetic stimulation is an effective treatment for dysphagia in Parkinson’s disease. However, the therapeutic effect and underlying mechanism of repetitive transcranial magnetic stimulation for dysphagia in Parkinson’s disease are still unknown. Neuroinflammation has been proven to be associated with dysphagia in Parkinson’s disease, and NLRP3 inflammasome activation and pyroptosis are common neuroinflammatory processes. Therefore, we compared swallowing quality, NLRP3 inflammasome activation, and caspase-1 dependent pyroptosis among NS control, repetitive transcranial magnetic stimulation control, sham repetitive transcranial magnetic stimulation control, and L-Dopa control mice by tongue muscle tone detection, immunohistochemistry, immunofluorescence, western blotting, co-immunoprecipitation, and quantitative PCR. The results showed that NLRP3 inflammasome activation and caspase-1-dependent pyroptosis were involved in dysphagia in MPTP-induced Parkinson’s disease mice model. Repetitive transcranial magnetic stimulation and L-dopa inhibited the above two pathways to alleviate dopaminergic neuronal damage and improve the quality of dysphagia. Repetitive transcranial magnetic stimulation (1 Hz, 1 time/3 days, 6 weeks) had the same effect on dysphagia as L-Dopa treatment (25 mg/kg/day, 6 weeks). Finally, we conclude that repetitive transcranial magnetic stimulation will be the preferred option for the treatment of dysphagia in Parkinson’s disease in certain conditions such as motor complications secondary to L-Dopa and L-Dopa non-response dysphagia.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"2014 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986360","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":"Multimodal neuroimaging to characterize symptom-specific networks in movement disorders.","authors":"Elizabeth G Ellis, Garance M Meyer, Valtteri Kaasinen, Daniel T Corp, Nicola Pavese, Martin M Reich, Juho Joutsa","doi":"10.1038/s41531-024-00774-3","DOIUrl":"10.1038/s41531-024-00774-3","url":null,"abstract":"<p><p>Movement disorders, such as Parkinson's disease, essential tremor, and dystonia, are characterized by their predominant motor symptoms, yet diseases causing abnormal movement also encompass several other symptoms, including non-motor symptoms. Here we review recent advances from studies of brain lesions, neuroimaging, and neuromodulation that provide converging evidence on symptom-specific brain networks in movement disorders. Although movement disorders have traditionally been conceptualized as disorders of the basal ganglia, cumulative data from brain lesions causing parkinsonism, tremor and dystonia have now demonstrated that this view is incomplete. Several recent studies have shown that lesions causing a given movement disorder occur in heterogeneous brain locations, but disrupt common brain networks, which appear to be specific to each motor phenotype. In addition, findings from structural and functional neuroimaging in movement disorders have demonstrated that brain abnormalities extend far beyond the brain networks associated with the motor symptoms. In fact, neuroimaging findings in each movement disorder are strongly influenced by the constellation of patients' symptoms that also seem to map to specific networks rather than individual anatomical structures or single neurotransmitters. Finally, observations from deep brain stimulation have demonstrated that clinical changes, including both symptom improvement and side effects, are dependent on the modulation of large-scale networks instead of purely local effects of the neuromodulation. Combined, this multimodal evidence suggests that symptoms in movement disorders arise from distinct brain networks, encouraging multimodal imaging studies to better characterize the underlying symptom-specific mechanisms and individually tailor treatment approaches.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"10 1","pages":"154"},"PeriodicalIF":6.7,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982930","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":"Standardized wireless deep brain stimulation system for mice","authors":"Alexander Grotemeyer, Tobias Petschner, Robert Peach, Dirk Hoehl, Torsten Knauer, Uwe Thomas, Heinz Endres, Robert Blum, Michael Sendtner, Jens Volkmann, Chi Wang Ip","doi":"10.1038/s41531-024-00767-2","DOIUrl":"https://doi.org/10.1038/s41531-024-00767-2","url":null,"abstract":"<p>Deep brain stimulation (DBS) has emerged as a revolutionary technique for accessing and modulating brain circuits. DBS is used to treat dysfunctional neuronal circuits in neurological and psychiatric disorders. Despite over two decades of clinical application, the fundamental mechanisms underlying DBS are still not well understood. One reason is the complexity of in vivo electrical manipulation of the central nervous system, particularly in rodent models. DBS-devices for freely moving rodents are typically custom-designed and not commercially available, thus making it difficult to perform experimental DBS according to common standards. Addressing these challenges, we have developed a novel wireless microstimulation system for deep brain stimulation (wDBS) tailored for rodents. We demonstrate the efficacy of this device for the restoration of behavioral impairments in hemiparkinsonian mice through unilateral wDBS of the subthalamic nucleus. Moreover, we introduce a standardized and innovative pipeline, integrating machine learning techniques to analyze Parkinson’s disease-like and DBS-induced gait changes.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"11 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980973","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":"A worldwide study of white matter microstructural alterations in people living with Parkinson’s disease","authors":"Conor Owens-Walton, Talia M. Nir, Sarah Al-Bachari, Sonia Ambrogi, Tim J. Anderson, Ítalo Karmann Aventurato, Fernando Cendes, Yao-Liang Chen, Valentina Ciullo, Phil Cook, John C. Dalrymple-Alford, Michiel F. Dirkx, Jason Druzgal, Hedley C. A. Emsley, Rachel Guimarães, Hamied A. Haroon, Rick C. Helmich, Michele T. Hu, Martin E. Johansson, Ho Bin Kim, Johannes C. Klein, Max Laansma, Katherine E. Lawrence, Christine Lochner, Clare Mackay, Corey T. McMillan, Tracy R. Melzer, Leila Nabulsi, Ben Newman, Peter Opriessnig, Laura M. Parkes, Clelia Pellicano, Fabrizio Piras, Federica Piras, Lukas Pirpamer, Toni L. Pitcher, Kathleen L. Poston, Annerine Roos, Lucas Scárdua Silva, Reinhold Schmidt, Petra Schwingenschuh, Marian Shahid-Besanti, Gianfranco Spalletta, Dan J. Stein, Sophia I. Thomopoulos, Duygu Tosun, Chih-Chien Tsai, Odile A. van den Heuvel, Eva van Heese, Daniela Vecchio, Julio E. Villalón-Reina, Chris Vriend, Jiun-Jie Wang, Yih-Ru Wu, Clarissa Lin Yasuda, Paul M. Thompson, Neda Jahanshad, Ysbrand van der Werf","doi":"10.1038/s41531-024-00758-3","DOIUrl":"https://doi.org/10.1038/s41531-024-00758-3","url":null,"abstract":"<p>The progression of Parkinson’s disease (PD) is associated with microstructural alterations in neural pathways, contributing to both motor and cognitive decline. However, conflicting findings have emerged due to the use of heterogeneous methods in small studies. Here we performed a large diffusion MRI study in PD, integrating data from 17 cohorts worldwide, to identify stage-specific profiles of white matter differences. Diffusion-weighted MRI data from 1654 participants diagnosed with PD (age: 20–89 years; 33% female) and 885 controls (age: 19–84 years; 47% female) were analyzed using the ENIGMA-DTI protocol to evaluate white matter microstructure. Skeletonized maps of fractional anisotropy (FA) and mean diffusivity (MD) were compared across Hoehn and Yahr (HY) disease groups and controls to reveal the profile of white matter alterations at different stages. We found an enhanced, more widespread pattern of microstructural alterations with each stage of PD, with eventually lower FA and higher MD in almost all regions of interest: Cohen’s d effect sizes reached <i>d</i> = −1.01 for FA differences in the fornix at PD HY Stage 4/5. The early PD signature in HY stage 1 included higher FA and lower MD across the entire white matter skeleton, in a direction opposite to that typical of other neurodegenerative diseases. FA and MD were associated with motor and non-motor clinical dysfunction. While overridden by degenerative changes in the later stages of PD, early PD is associated with paradoxically higher FA and lower MD in PD, consistent with early compensatory changes associated with the disorder.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"72 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915209","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}