Parkinsonism & related disorders最新文献

{"title":"Comparative pharmacokinetics of levodopa–carbidopa intestinal gel infusion and foslevodopa–foscarbidopa continuous subcutaneous infusion therapies in advanced Parkinson's disease","authors":"Yohei Mukai ,&nbsp;Junko Takei ,&nbsp;Juri Nomoto ,&nbsp;Motohiro Okumura ,&nbsp;Shinji Oda ,&nbsp;Tasuku Ishihara ,&nbsp;Yuka Hama ,&nbsp;Hotake Takizawa ,&nbsp;Toru Yamakawa ,&nbsp;Fumiko Furukawa ,&nbsp;Jun Shinmi ,&nbsp;Shoya Inagawa ,&nbsp;Shuho Namatame ,&nbsp;Yuji Takahashi","doi":"10.1016/j.parkreldis.2026.108197","DOIUrl":"10.1016/j.parkreldis.2026.108197","url":null,"abstract":"<div><h3>Introduction</h3><div>Levodopa–carbidopa intestinal gel therapy (LCIG) and foslevodopa–foscarbidopa continuous subcutaneous infusion therapy (FOCS) are device-aided therapies for advanced Parkinson's disease. Comparative real-world pharmacokinetic (PK) data remain limited. This study aimed to compare overall plasma levodopa exposure between LCIG and FOCS.</div></div><div><h3>Methods</h3><div>Patients who initiated LCIG or FOCS, completed dose optimization, and underwent a standardized levodopa challenge were evaluated. Plasma levodopa concentrations and motor states were assessed repeatedly over 420 min. Overall concentrations were compared using a linear mixed-effects model. Steady-state concentration (SSConc; 300–420 min) and its relationship with body-surface-area–adjusted infusion rate were examined. Time to On and the plasma concentration at On transition (On-Conc) were analyzed.</div></div><div><h3>Results</h3><div>Mean plasma levodopa concentrations tended to be higher with FOCS, although the group effect was not significant (geometric mean ratio: 1.38; p = 0.060). SSConc was higher with FOCS (12.85 ± 2.78 vs. 9.23 ± 1.61 nmol/mL). Both therapies showed linear SSConc–dose relationships, with a steeper slope for FOCS. LCIG produced a faster transition to the On state (median 45 vs. 150 min), whereas On-Conc was similar between groups (approximately 10 nmol/mL). In the FOCS group, baseline Off occurred only when nighttime infusion rates were ≤74 % of daytime rates.</div></div><div><h3>Conclusion</h3><div>LCIG and FOCS show distinct PK profiles despite similar overall concentrations. LCIG provides a rapid rise in levodopa levels and earlier On onset, whereas FOCS yields higher SSConc values and greater dose–concentration efficiency, informing titration approaches, nighttime infusion settings, and individualized selection of continuous infusion-based dopaminergic therapy.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"144 ","pages":"Article 108197"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Motor-planning cerebello-cerebral network alterations in PRRT2-related paroxysmal kinesigenic dyskinesia","authors":"Weihao Liao ,&nbsp;Yingying Zhang ,&nbsp;Jiechuan Ren ,&nbsp;Xiang Huang ,&nbsp;Qiuxing Lin ,&nbsp;Kailing Huang ,&nbsp;Yuming Li ,&nbsp;Peiwen Liu ,&nbsp;Danyang Cao ,&nbsp;Wenhao Li ,&nbsp;Xiuli Li ,&nbsp;Tianhua Yang ,&nbsp;Qiyong Gong ,&nbsp;Dongmei An ,&nbsp;Dong Zhou","doi":"10.1016/j.parkreldis.2026.108195","DOIUrl":"10.1016/j.parkreldis.2026.108195","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Emerging preclinical evidence suggests that the cerebellum plays a critical role in paroxysmal kinesigenic dyskinesia (PKD) associated with proline-rich transmembrane protein 2 (<em>PRRT2</em>) mutations. This study aimed to investigate the role of cerebello-cerebral network in PKD patients with <em>PRRT2</em> mutations (PKD-M) and PKD patients with no <em>PRRT2</em> mutations (PKD-N).</div></div><div><h3>Methods</h3><div>Resting-state functional magnetic resonance imaging scan was performed on 105 PKD patients (47 PKD-M and 58 PKD-N) and 62 healthy controls (HC). For seed-based functional connectivity (FC) analysis, the cerebellum was parcellated into 10 function-related regions through a functional atlas of the human cerebellum obtained by a multi-domain task battery. The cerebello-cerebral FC and regional homogeneity (ReHo) were examined using one-way analysis of covariance and two-sample <em>t</em>-test in PKD-M, PKD-N and HC.</div></div><div><h3>Results</h3><div>PKD-M had increased FC between a motor-planning related cerebellar region (region 4) and the middle cingulate gyrus, compared to HC. While PKD-M had decreased FC between this region and the lingual gyrus, compared to HC. PKD-M had increased FC between another cerebellar region (region 8) and the right inferior temporal gyrus/right superior frontal gyrus, compared to PKD-N. Additionally, PKD-M had decreased ReHo in the pons and the cerebellum anterior lobe and increased ReHo in the right inferior temporal gyrus, compared to HC.</div></div><div><h3>Conclusions</h3><div><em>PRRT2</em> mutations may cause abnormalities in a motor-planning cerebello-cerebral network, which likely play a major role in the pathogenesis of PKD-M.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"144 ","pages":"Article 108195"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of cardiovascular disease on Parkinson's disease: Findings from the PPMI study","authors":"Mehrbod Vakhshoori ,&nbsp;Niloofar Bondariyan ,&nbsp;Jacob Jones ,&nbsp;Zoltan Mari ,&nbsp;Farzin Pedouim ,&nbsp;Khashayar Dashtipour","doi":"10.1016/j.parkreldis.2026.108210","DOIUrl":"10.1016/j.parkreldis.2026.108210","url":null,"abstract":"<div><h3>Background</h3><div>Parkinson's disease (PD) is a neurodegenerative disorder in which age is the strongest risk factor, but the role of cardiovascular disease (CVD) remains unclear. This study examines the impact of CVD history on PD onset and progression.</div></div><div><h3>Methods</h3><div>We conducted a cross-sectional analysis using data from the Parkinson's Progression Markers Initiative (PPMI), involving 1109 participants (924 PD patients and 185 healthy controls). The correlation of CVD history with PD and its progression (motor and non-motor symptoms assessed with Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS I-IV), autonomic dysfunction assessed with Scales for Outcomes in PD–Autonomic Dysfunction (SCOPA-AUT), and cognitive impairment assessed with Montreal Cognitive Assessment (MoCA)) was evaluated using regression models.</div></div><div><h3>Results</h3><div>Participants had a mean age of 62.84 ± 9.64 years (61 % male), with no significant group differences in CVD history (P = 0.382). CVD history was not associated with PD occurrence, even after matched comparison. PD participants were predominantly early-stage with a mean follow-up of 4.84 ± 4.67 years. CVD history showed no association with autonomic or cognitive outcomes but was associated with a higher risk of motor complications (MDS-UPDRS IV: OR:3.34, 95 %CI:1.38–8.63, P = 0.009), with no effects on other MDS-UPDRS categories; progression-based analyses likewise showed no impact on autonomic or cognitive function (P &gt; 0.05).</div></div><div><h3>Conclusions</h3><div>CVD history does not independently predict PD incidence or autonomic or cognitive progression but may increase the risk of motor complications. These findings should be interpreted cautiously due to the predominance of early-stage PD patients and small subgroup sizes, and require further validation.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"144 ","pages":"Article 108210"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lifting the veil: Interpreting phenotypic fluidity in functional movement disorders","authors":"Saar Anis,&nbsp;Megan Zelinsky,&nbsp;Umar Shuaib,&nbsp;Xin Xin Yu","doi":"10.1016/j.parkreldis.2026.108221","DOIUrl":"10.1016/j.parkreldis.2026.108221","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"144 ","pages":"Article 108221"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring regional BOLD fluctuations to understand the pathophysiology of mild cognitive impairments in individuals with Parkinson's disease","authors":"Narayan D. Chaurasiya ,&nbsp;Taylor Davis ,&nbsp;Gaurav N. Rathi ,&nbsp;Jessica ZK. Caldwell ,&nbsp;Aaron Ritter ,&nbsp;Zoltan Mari ,&nbsp;Virendra R. Mishra","doi":"10.1016/j.parkreldis.2026.108177","DOIUrl":"10.1016/j.parkreldis.2026.108177","url":null,"abstract":"<div><h3>Introduction</h3><div>This study investigated whether z-standardized fractional amplitude of low-frequency fluctuations (zfALFF) and z-standardized regional homogeneity (zKcc ReHo) capture functional brain alterations associated with mild cognitive impairment (MCI) in Parkinson's disease (PD) and their relationships with clinical and cognitive measures.</div></div><div><h3>Methods</h3><div>Forty-seven participants (16 healthy controls [HC], 31 with PD) were recruited, with MCI identified using Litvan's criteria. After preprocessing, 45 participants were analyzed: HC (n = 15), PD with normal cognition (PD-NC, n = 12), and PD with MCI (PD-MCI, n = 18). Voxelwise zfALFF and zKcc ReHo maps were examined using nonparametric regression (PALM) for group differences and associations with disease duration, medication dose (LEDD), motor severity (UPDRS-III ON), and cognitive domains, adjusting for demographic and brain volume factors (FDR p &lt; 0.05).</div></div><div><h3>Results</h3><div>PD-MCI showed reduced zfALFF and zKcc ReHo in frontoparietal and midline regions linked to executive and default mode networks, while PD-NC exhibited increased activity and synchrony in subcortical–frontal and occipital areas. In PD-MCI, LEDD correlated positively with both metrics in frontostriatal and occipitotemporal regions; UPDRS-ON correlated positively with zKcc ReHo. In PD-NC, UPDRS-ON correlated positively with zfALFF in attention-related areas. Cognitive analyses indicated executive attention coupling in PD-NC and memory-related changes in PD-MCI.</div></div><div><h3>Conclusions</h3><div>zfALFF and zKcc ReHo reveal stage-specific alterations in neural activity and synchrony in PD that reflect disease severity and cognitive vulnerability, highlighting their promise as complementary neuroimaging biomarkers<strong>.</strong></div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"144 ","pages":"Article 108177"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145904015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On thin ice: sequence effect drifts toward freezing of gait","authors":"Ihtsham U. Haq","doi":"10.1016/j.parkreldis.2026.108182","DOIUrl":"10.1016/j.parkreldis.2026.108182","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"144 ","pages":"Article 108182"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amantadine: a first option for symptomatic relief in young-onset Parkinson's disease?","authors":"Hyeyoung Park ,&nbsp;Bastiaan R. Bloem ,&nbsp;Beomseok Jeon","doi":"10.1016/j.parkreldis.2026.108215","DOIUrl":"10.1016/j.parkreldis.2026.108215","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"144 ","pages":"Article 108215"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parkinson's disease with and without history of Agent Orange exposure: A prospective study of US Veterans","authors":"Vivikta Iyer ,&nbsp;Cole Zweber ,&nbsp;Ian Zurlo ,&nbsp;Pedram Golnari ,&nbsp;Katrina Prantzalos ,&nbsp;Brenna M. Lobb ,&nbsp;Dakota Clarke ,&nbsp;James T. Boyd ,&nbsp;Satya S. Sahoo ,&nbsp;Curtis Tatsuoka ,&nbsp;Deepak K. Gupta ,&nbsp;Amie L. Hiller","doi":"10.1016/j.parkreldis.2026.108220","DOIUrl":"10.1016/j.parkreldis.2026.108220","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"144 ","pages":"Article 108220"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuromelanin-sensitive MRI as a biomarker for individualized deep brain stimulation in Parkinson's disease: Associations between substantia nigra imaging and therapeutic outcomes","authors":"Yinling Zhou ,&nbsp;Yindi Zhang ,&nbsp;Guo Li ,&nbsp;Wei Zhang","doi":"10.1016/j.parkreldis.2026.108205","DOIUrl":"10.1016/j.parkreldis.2026.108205","url":null,"abstract":"<div><h3>Background</h3><div>Deep brain stimulation (DBS) of the subthalamic nucleus (STN) effectively treats advanced Parkinson's disease (PD), yet motor and non-motor outcomes vary considerably. Neuromelanin-sensitive MRI (NM-MRI) visualizes dopaminergic neuron loss in the substantia nigra pars compacta (SNc) and may serve as a predictive biomarker.</div></div><div><h3>Objectives</h3><div>To explore quantitative associations between preoperative NM-MRI SNc characteristics and postoperative clinical improvement in PD patients undergoing STN-DBS.</div></div><div><h3>Methods</h3><div>In this prospective cohort study, 33 PD patients scheduled for bilateral STN-DBS and 16 age-matched healthy controls were enrolled. Clinical outcomes at 3 months post-surgery included percentage improvement in Unified PD Rating Scale Part III (UPDRS-III), PD Questionnaire-39 (PDQ-39), and levodopa equivalent daily dose (LEDD). High-resolution T1-weighted and NM-sensitive sequences were acquired at 3.0 T; SNc volume and signal-to-noise ratio (SNR) were calculated after manual region-of-interest delineation.</div></div><div><h3>Results</h3><div>Contralesional SNc volume and SNR were significantly reduced versus ipsilesional sides (both P &lt; 0.001) and controls (P = 0.043 and P = 0.031). Contralesional SNc volume correlated moderately with UPDRS-III improvement (r = 0.508, P = 0.003), whereas SNR correlated strongly with PDQ-39 improvement (r = 0.599, P &lt; 0.001). Multivariable regression confirmed contralesional volume as an independent predictor of motor response and SNR of quality-of-life response. ROC analysis yielded AUCs of 0.785 for volume predicting good motor outcome and 0.724 for SNR predicting good quality-of-life outcome, increasing to 0.800 and 0.786 when combined with Hoehn-Yahr stage.</div></div><div><h3>Conclusion</h3><div>Preoperative NM-MRI-derived SNc volume and SNR are robust, non-invasive biomarkers for predicting motor and quality-of-life responses to STN-DBS, supporting personalized patient selection and precision neuromodulation in Parkinson's disease. Larger longitudinal studies are warranted.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"144 ","pages":"Article 108205"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrocephalus should not be a mandatory exclusion criterion in PSP: Emerging pathologic and clinical evidence urges reconsideration","authors":"Halil Onder","doi":"10.1016/j.parkreldis.2026.108183","DOIUrl":"10.1016/j.parkreldis.2026.108183","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"144 ","pages":"Article 108183"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}