NPJ Parkinson's Disease最新文献_第3页

Longitudinal assessment of the association between pesticide exposure and lifestyle with Parkinson’s disease motor severity 农药暴露和生活方式与帕金森病运动严重程度之间关系的纵向评估

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-06-12 DOI: 10.1038/s41531-025-01010-2

Theresa Lüth, Amke Caliebe, Carolin Gabbert, Sebastian Sendel, Björn-Hergen Laabs, Inke R. König, Christine Klein, Joanne Trinh

{"title":"Longitudinal assessment of the association between pesticide exposure and lifestyle with Parkinson’s disease motor severity","authors":"Theresa Lüth, Amke Caliebe, Carolin Gabbert, Sebastian Sendel, Björn-Hergen Laabs, Inke R. König, Christine Klein, Joanne Trinh","doi":"10.1038/s41531-025-01010-2","DOIUrl":"https://doi.org/10.1038/s41531-025-01010-2","url":null,"abstract":"Longitudinal investigations on the relationship between lifestyle exposures and motor severity are lacking. In this longitudinal study, we included patients with idiopathic Parkinson’s disease (iPD) (N = 5139) and LRRK2-related PD (N = 81) from PPMI-Online and Fox Insight. Motor aspects were followed for up to five years. We investigated the association between environmental exposure, lifestyle factors and motor aspect severity over time by applying linear mixed effects models. In LRRK2-PD, black tea consumption was associated with less severe motor aspects (β = −0.51, p = 0.028). In patients with iPD, pesticide exposure was associated with more severe motor aspects over time in PPMI-Online (β = 0.23, p = 3.56 × 10−9). Lastly, caffeinated soda was associated with more severe motor aspects in patients with iPD from PPMI-Online (β = 0.15, p = 3.84 × 10−8) and Fox Insight (β = 0.09, p = 0.031). We suggest that pesticide exposure and lifestyle factors may affect motor severity in patients with LRRK2-PD and iPD, demonstrating the impact on patients even after disease onset.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"26 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278721","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}

引用次数: 0

Clinical correlates of data-driven subtypes of deep gray matter atrophy and dopamine availability in early Parkinson’s disease 数据驱动的深部灰质萎缩亚型与早期帕金森病多巴胺可用性的临床相关性

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-06-12 DOI: 10.1038/s41531-025-01037-5

Yoonsang Oh, Joong-Seok Kim, Gilsoon Park, Sang-Won Yoo, Dong-Woo Ryu, Hosung Kim

{"title":"Clinical correlates of data-driven subtypes of deep gray matter atrophy and dopamine availability in early Parkinson’s disease","authors":"Yoonsang Oh, Joong-Seok Kim, Gilsoon Park, Sang-Won Yoo, Dong-Woo Ryu, Hosung Kim","doi":"10.1038/s41531-025-01037-5","DOIUrl":"https://doi.org/10.1038/s41531-025-01037-5","url":null,"abstract":"Recent machine-learning techniques may be useful to identify subtypes with distinct spatial patterns of biomarker abnormality in the various neurodegenerative diseases. Using the Subtype and Stage Inference (SuStaIn) technique, we categorized data-driven subtypes of PD by examining the deep gray matter volume and dopamine availability and compared cardiac denervation, cognition, and motor symptoms between these subtypes. The SuStaIn algorithm revealed two distinctive subtypes, which were well replicated in an external dataset. Subtype 1 was characterized by lower dopamine availability apparent at early inferred stages, severe cardiac denervation, mild cognitive dysfunction in the early stage, and patterns suggesting accelerated motor and cognitive dysfunction associated with later stages. In contrast, subtype 2 showed patterns indicative of earlier brain atrophy, mild cardiac denervation, and severe cognitive dysfunction apparent at early inferred stages, with no significant correlation between motor and cognitive status and SuStaIn stage. These findings suggest that the machine-learning model can identify heterogeneity in PD biomarker profiles, offering insights into potential region and stage-specific patterns of biomarker abnormality and their clinical implications.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"10 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278723","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}

引用次数: 0

Lipid profiling of Parkinson’s disease brain highlights disruption in Lysophosphatidylcholines, and triacylglycerol metabolism 帕金森病脑脂质分析强调溶血磷脂酰胆碱和三酰甘油代谢的破坏

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-06-11 DOI: 10.1038/s41531-025-01023-x

Ali Yilmaz, Nadia Ashrafi, Romana Ashrafi, Sumeyya Akyol, Nazia Saiyed, Ieva Kerševičiūtė, Migle Gabrielaite, Juozas Gordevicius, Stewart F. Graham

引用次数: 0

Glymphatic dysfunction evidenced by DTI-ALPS is related to obstructive sleep apnea intensity in newly diagnosed Parkinson’s disease DTI-ALPS证明的淋巴功能障碍与新诊断帕金森病的阻塞性睡眠呼吸暂停强度有关

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-06-11 DOI: 10.1038/s41531-025-01018-8

Jiri Nepozitek, Stanislav Marecek, Veronika Rottova, Simona Dostalova, Tomas Krajca, Jiri Keller, Karel Sonka, Petr Dusek

{"title":"Glymphatic dysfunction evidenced by DTI-ALPS is related to obstructive sleep apnea intensity in newly diagnosed Parkinson’s disease","authors":"Jiri Nepozitek, Stanislav Marecek, Veronika Rottova, Simona Dostalova, Tomas Krajca, Jiri Keller, Karel Sonka, Petr Dusek","doi":"10.1038/s41531-025-01018-8","DOIUrl":"https://doi.org/10.1038/s41531-025-01018-8","url":null,"abstract":"Glymphatic dysfunction potentially contributes to Parkinson’s disease (PD) via impaired clearance of metabolic waste products. Obstructive sleep apnea (OSA) can disturb sleep, which is necessary for proper glymphatic function, and is frequent in PD. We investigated the glymphatic function in de novo PD and its relation to OSA. Fifty-four PD patients (mean age 58.9 ± 12.2 years) and 32 controls (mean age 59.4 ± 8.3 years) underwent polysomnography and 3 T magnetic resonance imaging of the brain. Diffusion tensor imaging along the perivascular space (DTI-ALPS) was calculated using atlas-based automatic regions of interest selection. In PD, ALPS-index negatively correlated with apnea-hypopnea index (rho = −0.41; p = 0.002), oxygen desaturation index (rho = −0.38; p = 0.006), sleep stage N1 (rho = −0.42; p = 0.002), and arousal index (rho = −0.24; p = 0.018), while in controls, no such correlations were observed. Glymphatic dysfunction is related to OSA severity in de novo PD but not in controls. We suggest that OSA may contribute to neurodegeneration via glymphatic impairment in PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"4 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260399","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}

引用次数: 0

L-Dopa-induced changes in aperiodic bursts dynamics relate to individual clinical improvement in Parkinson’s disease 左旋多巴诱导的非周期性爆发动力学变化与帕金森病个体临床改善有关

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-06-10 DOI: 10.1038/s41531-025-01024-w

Hasnae Agouram, Matteo Neri, Marianna Angiolelli, Damien Depannemaecker, Jyotika Bahuguna, Antoine Schwey, Jean Régis, Romain Carron, Nicole Malfait, Alexandre Eusebio, Emmanuel Daucé, Pierpaolo Sorrentino

{"title":"L-Dopa-induced changes in aperiodic bursts dynamics relate to individual clinical improvement in Parkinson’s disease","authors":"Hasnae Agouram, Matteo Neri, Marianna Angiolelli, Damien Depannemaecker, Jyotika Bahuguna, Antoine Schwey, Jean Régis, Romain Carron, Nicole Malfait, Alexandre Eusebio, Emmanuel Daucé, Pierpaolo Sorrentino","doi":"10.1038/s41531-025-01024-w","DOIUrl":"https://doi.org/10.1038/s41531-025-01024-w","url":null,"abstract":"Parkinson’s disease (PD) is a neurodegenerative disease characterized by severe motor symptoms, transiently alleviated by medication (e.g. levodopa), and widespread brain activity alterations that remain poorly understood at a large scale level. To address this issue, we used resting-state STN-DBS and motor EEG data from 11 PD patients before and after levodopa treatment. Neuronal avalanches, i.e., brief, widespread bursts of activities, were detected and compared across the two conditions. Interestingly, we noted shorter and smaller avalanches in the OFF-condition and fewer, longer, and larger avalanches in the ON-condition. We then computed the avalanche transition matrices to track the contact-wise patterns of avalanche spread. We found a significantly higher probability of avalanche spread within and between the STN and motor cortex in the ON-condition. Furthermore, increased propagation of avalanches correlated with clinical improvement. Our study identifies potential biomarkers for electrophysiological changes in PD through cross-modality assessment of aperiodic activities.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"24 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260290","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}

引用次数: 0

A new LRRK2 variant in a family with Parkinson’s disease affects binding to RAB8A 帕金森病患者家族中的一种新的LRRK2变体影响与RAB8A的结合

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-06-07 DOI: 10.1038/s41531-025-00989-y

Lydia Vela-Desojo, Alba Pascual, Victor Montal, Carmen Guerrero, Mireia Osuna-López, Victor Guallar, Francesc Palau, Janet Hoenicka

{"title":"A new LRRK2 variant in a family with Parkinson’s disease affects binding to RAB8A","authors":"Lydia Vela-Desojo, Alba Pascual, Victor Montal, Carmen Guerrero, Mireia Osuna-López, Victor Guallar, Francesc Palau, Janet Hoenicka","doi":"10.1038/s41531-025-00989-y","DOIUrl":"https://doi.org/10.1038/s41531-025-00989-y","url":null,"abstract":"Pathogenic variants in the LRRK2 gene affecting catalytic domains are the most common genetic cause of Parkinson’s disease (PD). Nevertheless, LRRK2 variants at the armadillo (ARM) domain would indirectly affect the protein’s activity by interacting with RAB proteins. We present a family with PD recurrence segregating the new LRRK2 allele at the ARM domain, p.[Leu.119Pro;Leu488Pro]. Clinical exams were conducted on nine relatives. Neuropathology of the index case showed loss of substantia nigra neurons and Alzheimer’s disease-type lesions. In silico analysis of the p.[Leu.119Pro;Leu488Pro] LRRK2 variant predicted alterations in ARM tertiary structure and binding affinity. These predictions were supported by functional genomics using recombinant LRRK2WT and LRRK2Leu119Pro;Leu488Pro. We found increased interaction between LRRK2Leu119Pro;Leu488Pro and RAB8A, but not with RAB10. Additionally, docking studies revealed stronger affinity of LRRK2Leu119Pro;Leu488Pro for RAB8A (P < 0.0001) and allosteric properties beyond the mutated residues. We propose p.[Leu119Pro;Leu488Pro] as a cause of familial PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"18 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236982","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}

引用次数: 0

EGFR phosphorylates DNAJB1 to suppress α-synuclein aggregation in Parkinson’s disease EGFR磷酸化DNAJB1抑制帕金森病α-突触核蛋白聚集

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-06-07 DOI: 10.1038/s41531-025-01006-y

Yun-Yu Huang, Sue-Jane Lin, Wei-Yu Chiang, Yuan-Teng Chang, Chan-Chih Yang, Chia-Yu Liao, Ya-Lan Chang, Chin-Hsien Lin, Shu-Chun Teng

引用次数: 0

Brain-clinical biotyping in patients with idiopathic REM sleep behavior disorder 特发性REM睡眠行为障碍患者的脑临床生物分型研究

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-06-07 DOI: 10.1038/s41531-025-01012-0

Shi Tang, Bei Huang, Yanlin Wang, Yaping Liu, Jing Wang, Li Zhou, Siyi Gong, Yuhua Yang, Joey WY Chan, Steven WH Chau, Winnie CW Chu, Jill Abrigo, Jean-François Gagnon, Yun Kwok Wing

{"title":"Brain-clinical biotyping in patients with idiopathic REM sleep behavior disorder","authors":"Shi Tang, Bei Huang, Yanlin Wang, Yaping Liu, Jing Wang, Li Zhou, Siyi Gong, Yuhua Yang, Joey WY Chan, Steven WH Chau, Winnie CW Chu, Jill Abrigo, Jean-François Gagnon, Yun Kwok Wing","doi":"10.1038/s41531-025-01012-0","DOIUrl":"https://doi.org/10.1038/s41531-025-01012-0","url":null,"abstract":"Idiopathic REM sleep behavior disorder (iRBD) is a prodromal stage of α-synucleinopathies including Parkinson’s disease (PD), yet its clinical heterogeneity remains underexplored. This study aimed to identify novel brain-clinical biotypes in iRBD by integrating structural MRI and clinical assessments. We included 172 patients with video-polysomnography-confirmed iRBD and 126 controls who underwent multimodal MRI and clinical evaluation. Similarity Network Fusion was used to integrate cortical thickness, surface area, subcortical volume, and clinical data, followed by spectral clustering to identify iRBD biotypes. Two distinct biotypes were identified: Biotype 1 showed widespread cortical-subcortical-cerebellar atrophy, functional hypoconnectivity, more motor and cognitive deficits with higher prodromal PD risk; Biotype 2 demonstrated increased surface area in limbic and parietal regions, cortical-cerebellar hyperconnectivity, and preserved neurocognitive function. These findings underscore the presence of distinct neurobiological subtypes in iRBD, highlighting the need for longitudinal monitoring to clarify their trajectories and implications for disease progression.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"70 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237421","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}

引用次数: 0

Peripheral inflammation’s variable impact on cognitive and symptomatic outcomes in Parkinson’s disease: a longitudinal and cross-sectional analysis 外周炎症对帕金森病认知和症状结局的可变影响：纵向和横断面分析

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-06-07 DOI: 10.1038/s41531-025-01019-7

Peikun He, Yanyi Li, Zhiheng Huang, Yuyuan Gao, Qingrui Duan, Yihui Qiu, Shujun Feng, Ruiyun Huang, Liangxu Gong, Guixian Ma, Yuhu Zhang, Lin Shi, Lijuan Wang, Kun Nie

{"title":"Peripheral inflammation’s variable impact on cognitive and symptomatic outcomes in Parkinson’s disease: a longitudinal and cross-sectional analysis","authors":"Peikun He, Yanyi Li, Zhiheng Huang, Yuyuan Gao, Qingrui Duan, Yihui Qiu, Shujun Feng, Ruiyun Huang, Liangxu Gong, Guixian Ma, Yuhu Zhang, Lin Shi, Lijuan Wang, Kun Nie","doi":"10.1038/s41531-025-01019-7","DOIUrl":"https://doi.org/10.1038/s41531-025-01019-7","url":null,"abstract":"Increasing evidence supported a link between peripheral inflammation and Parkinson’s disease (PD). However, the role of peripheral inflammation in the progression of PD clinical symptoms remained unclear. This study evaluates peripheral inflammation using serum differential leukocyte counts and their derived ratios. A total of 170 PD patients were retrospectively enrolled from Guangdong Provincial People’s Hospital (GDPH) and 68 from PPMI. Partial correlation analysis showed that neutrophil-to-lymphocyte ratio (NLR) negatively correlated with MoCA in GDPH but not in PPMI. Moreover, peripheral inflammation was shown to correlate with white matter integrity. The result of the longitudinal analysis showed that higher baseline NLR predicted worsening in letter number sequencing (LNS) score. Path analysis indicated that white matter integrity significantly mediated the relationship between NLR and cognitive change in the LNS score from Year 5 to baseline. Peripheral inflammation is associated with global cognition and white matter integrity in PD and predicts cognitive decline.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"6 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237135","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}

引用次数: 0

Optimizing wrist-worn wearable compliance with insights from two Parkinson’s disease cohort studies 根据两项帕金森病队列研究的见解优化腕戴式可穿戴设备的依从性

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2025-06-06 DOI: 10.1038/s41531-025-01016-w

Marjan J. Meinders, Laura Heathers, King Chung Ho, Laura Russell, Chris Li, Bastiaan R. Bloem, William J. Marks Jr, Ritu Kapur

{"title":"Optimizing wrist-worn wearable compliance with insights from two Parkinson’s disease cohort studies","authors":"Marjan J. Meinders, Laura Heathers, King Chung Ho, Laura Russell, Chris Li, Bastiaan R. Bloem, William J. Marks Jr, Ritu Kapur","doi":"10.1038/s41531-025-01016-w","DOIUrl":"https://doi.org/10.1038/s41531-025-01016-w","url":null,"abstract":"Wearable technologies enable real-time, continuous, noninvasive data collection, where long-term compliance is essential. The Personalized Parkinson Project (PPP) and the Parkinson’s Progression Markers Initiative (PPMI) utilized the Verily Study Watch. Participants, including people diagnosed with Parkinson’s disease (PD), prodromal PD, and healthy controls, were instructed to wear the watch for up to 23 h daily without data displaying or reporting data back to the participant. Compliance measures and user experiences were evaluated. A centralized support model identified barriers to data collection and enabled proactive outreach. Median daily wear time was 21.9 h for PPP and 21.1–22.2 h per day for PPMI over 2 years. Participants were highly motivated contributing to PD research. These results highlight strategies for achieving strong engagement without providing individual data. This approach offers valuable insights for study designs where returning data to participants could introduce bias or affect the data integrity.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"9 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228975","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}

引用次数: 0