Journal of neural transmission (Vienna, Austria : 1996)最新文献

{"title":"Development and clinical translation of smartphone-based digital biomarkers for Parkinson's disease: a structured review.","authors":"Onanong Phokaewvarangkul, Suppakorn Yamutai, Roongroj Bhidayasiri, Peerapon Vateekul, Decho Surangsrirat, Walter Maetzler, Andrea Pilotto, Chaewon Shin, Genko Oyama","doi":"10.1007/s00702-026-03269-y","DOIUrl":"https://doi.org/10.1007/s00702-026-03269-y","url":null,"abstract":"<p><p>Diagnosis of Parkinson's disease (PD) remains a major clinical challenge, particularly in the prodromal and early clinically evident stages, when symptoms are subtle and phenotypically overlap with other mimicking disorders. The widespread availability of smartphones equipped with inertial, acoustic, touchscreen, and geolocation sensors has enabled the emergence of smartphone-based digital biomarkers that capture continuous, real-world motor and non-motor manifestations of PD. To critically review the validation state, construct validity, clinical applications, and potential for longitudinal monitoring of smartphone-derived digital biomarkers for early PD detection and for differential diagnosis from mimicking disorders, while addressing methodological, regulatory, and implementation challenges. This manuscript reviews the current evidence on smartphone-based active and passive digital assessments for the early diagnosis and screening of PD. We examine clinical validation and implementation, as well as advances in technological processing, multimodal digital phenotyping, and machine learning models, for the early detection and screening of PD. Smartphone-derived digital markers demonstrate promising capability for detecting several symptoms and support early diagnosis of PD. A total of 30 studies showed significant correlations of such markers with established clinical scales and suggested utility in differentiating PD from other Parkinsonian syndromes and prodromal PD patients. Six major categories based on the clinical assessment were identified: 8 studies with voice-based assessment, 6 with touchscreen-based assessment, 4 with video-recording assessment, 4 with inertial measurement unit-based assessment, 7 with multimodal assessment approaches, and 1 with questionnaire-based smartphone assessment. However, substantial limitations persist, including device and protocol heterogeneity, limited external validation, small datasets, algorithmic bias, inadequate explainability, and inconsistent reporting standards. Smartphone-based digital biomarkers offer a promising approach to improving diagnostic accuracy in PD and are emerging as a frontier in precision neurology and scalable PD care. However, these findings have several limitations and should be interpreted with caution. Future research should prioritise multicentre longitudinal validation, multimodal integration, explainable AI, and real-world deployment to establish clinically actionable digital biomarkers for early PD detection and differential diagnosis.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of immersive gamification technology on the physical function of people with Parkinson's disease: a scoping review.","authors":"Maria Eliza R Aguila, Khervin Ian M Guitones, Martina Ysabel B Arellano, Mitchelet B Rivera, Isabela Marie B Evangelista, Mark Justine B Tanglao, Jeremy Russell P Ting, Angelic J Rabano, Christian Alfredo K Cruz, Ben Anthony A Lopez, Jaime D L Caro, Michael L Tee, Cherica A Tee, Veeda Michelle M Anlacan, Roland Dominic G Jamora","doi":"10.1007/s00702-026-03271-4","DOIUrl":"https://doi.org/10.1007/s00702-026-03271-4","url":null,"abstract":"<p><p>Conventional rehabilitation effectively manages physical impairments in Parkinson's disease (PD), but reduced motivation limits long-term adherence. Immersive gamification technology systems (ImGTS) offer an engaging, safe, and potentially effective approach to improve physical function. However, the scope and characteristics of current evidence remain unclear. This scoping review mapped the literature on the effects of ImGTS on physical function in people with PD. A Boolean search of six databases was conducted in March 2025, supplemented by backward snowballing, to identify all eligible English-language studies indexed up to the date of the search that involved people with PD and evaluated ImGTS for physical function outcomes. Data on study characteristics, population, intervention, comparison, outcomes, and key findings were charted using a standardized form. Screening, data charting, and methodological quality assessment were conducted independently by five reviewers, with disagreements resolved through consensus. Findings were synthesized narratively with descriptive statistics. Twenty-nine studies were included: randomized controlled trials (n = 10, 34.5%), pre-post intervention studies (n = 10, 34.5%), within-subject trials (n = 6, 20.7%), and cross-over trials (n = 3, 10.3%). Most of these studies had low (n = 18, 62.0%) to moderate (n = 10, 34.5%) risk of bias. Games were task-based, goal-oriented, recreational, and multi-level. Balance (n = 17, 58.6%) and gait (n = 16, 55.2%) consistently improved, whereas effects on upper extremity strength, coordination, and function were more variable. Similar platforms were often classified differently in terms of immersiveness, highlighting inconsistent reporting. ImGTS show promise for improving physical function in PD, but evidence is limited by methodological heterogeneity and inconsistent definitions. Future studies should adopt standardized definitions, robust study designs, and context-appropriate ImGTS frameworks.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The lived experience of Parkinson's disease in the Philippines: challenges, cultural constructs, and caregiving impacts.","authors":"Franzis Mari G Lawas, Jucelyn Hernani, Gerard Saranza, Dexter Dimaano, Joshua Emmanuel Abejero, Maritzie R Eribal, Maria Teresa Cañete, Marianne S Macias, Redentor Durano","doi":"10.1007/s00702-026-03270-5","DOIUrl":"https://doi.org/10.1007/s00702-026-03270-5","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms. Although its global burden is rising, PD remains underrecognized in low- and middle-income countries like the Philippines, where access to diagnosis, treatment, and support systems is limited. This research addresses the gap between clinical outcomes and the realities of patient care, thereby enabling the development of healthcare policies and the enhancement of healthcare delivery that meet the needs of both patients and caregivers. This study aims to explore the lived experiences of PD patients and their caregivers in Cebu Province, Philippines. A phenomenological qualitative design was employed. Data were gathered through structured and unstructured interviews and focus group discussions (FGDs) conducted during a Parkinson's Awareness event in April 2025. A total of 43 patients (mean age: 66.7 years, mostly male) and 32 caregivers (mean age: 53.8 years, mostly female) participated. Caregivers included family members/relatives and paid hired caregivers who provided ongoing assistance to persons living with Parkinson's disease. Given their differing relationships to the patient and care responsibilities, caregiver accounts were interpreted within this heterogeneous caregiving context. Thematic analysis, which was conducted manually, was guided by the constant comparative method and a standardized codebook. Five major themes emerged: (1) Acceptance and emotional adjustment to diagnosis; (2) Navigating treatment and healthcare systems; (3) Daily and emotional challenges; (4) Shifting family dynamics and caregiving roles; and (5) Limited community and institutional support. Filipino cultural values (hiya, kapwa, and pakikisama) significantly shaped caregiving responses and help-seeking behaviors. PD care in the Philippines is marked by psychological burden, caregiver strain, and systemic healthcare gaps. Culturally sensitive, multidisciplinary approaches are urgently needed, including expanded caregiver support, mental health services, and improved access to specialized care. MeSH Terms: Parkinson's Disease, caregivers, qualitative research, Philippines, Health Services Accessibility, family, caregiver burden, cultural constructs, social support, activities of daily living, quality of life.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuronal death and accumulation of lipid droplets and glycogen granules within retinal pigment epithelium under the influence of mTOR and autophagy.","authors":"Michela Ferrucci, Gloria Lazzeri, Roberto Pinelli, Francesca Biagioni, Violet Vakunseh Bumah, Maria A Giambelluca, Carla L Busceti, Paola Lenzi, Francesco Fornai","doi":"10.1007/s00702-026-03172-6","DOIUrl":"10.1007/s00702-026-03172-6","url":null,"abstract":"<p><p>In the course of age-related macular degeneration (AMD) the retinal pigment epithelium undergoes a number of cytopathological alterations that are generated by a dysfunction of specific metabolic pathways. In detail, these include lipid and glycogen accumulation along with dismantling of specific proteins from the plasma membrane. In the present study we analyzed whether 3-methyladenine (3-MA), a classic autophagy inhibitor, may reproduce the pathobiochemical and structural alterations occurring in AMD. Different doses of 3-MA produce a loss of cell viability with lipids and glycogen accumulation, which were quantified by ultrastructural morphometry. This was concomitant with displacement and suppression of autophagy-related proteins along with increased activity of mTOR. A dismantling of phenotype-specific proteins composing tight junctions was observed as well. All these alterations were reverted by the phytochemical autophagy stimulator curcumin which was shown to act as a powerful mTOR inhibitor with an efficacy that was like the classic mTOR inhibitor rapamycin. When these compounds activating autophagy/inhibiting mTOR were administered alone, a beneficial effect was observed even in control cells. The occurrence of 3-MA-induced retinal degeneration was found to be associated with a remarkable aggregation of p62 which is reminiscent of central neurodegenerative disorders, and it was fully prevented by curcumin similarly to rapamycin. These protective effects concern cell viability, altered glycogen and lipid accumulation, and ultrastructural alterations. The present work contributes to understanding degeneration in AMD while extending key biochemical steps to neurodegenerative disorders. The use of natural phytochemicals and light-induced by-products may be used for therapeutic purposes.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2443-2477"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CogStrat: web-based tools for predicting incident cognitive impairment in cognitively normal older adults.","authors":"Adolfo Jiménez-Huete, Jimmy Santiago Ulloa Bravo, Antonio Martín-Bastida, Teresa Rognoni, Genoveva Montoya-Murillo, María Cruz Rodríguez-Oroz, Mario Riverol","doi":"10.1007/s00702-026-03163-7","DOIUrl":"10.1007/s00702-026-03163-7","url":null,"abstract":"<p><p>Early identification of individuals at increased risk of cognitive impairment is crucial for timely intervention. We developed and evaluated Cox proportional hazards models and translated them into web-based applications to predict incident cognitive impairment in cognitively normal older adults using clinical data, with optional biomarker inputs. Data were drawn from cognitively unimpaired participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Models included demographic and neuropsychological variables, with optional genetic, neuroimaging, and fluid (plasma and CSF) biomarkers. Performance was assessed using the C-index, calibration slope, and decision curve analysis, with internal validation via bootstrap resampling. Key models were externally validated in the Harvard Aging Brain Study. The ADNI sample comprised 729 participants (median age 73 years; 45% male). A clinical model including age, education, Montreal Cognitive Assessment, and delayed word recall showed acceptable discrimination (C-index 0.721; CI 0.672-0.772) and strong calibration (slope 0.940). Adding biomarkers improved performance, with the highest discrimination observed for a model including FDG and florbetapir PET uptake (C-index 0.805; CI 0.759-0.886). Discrimination remained stable after internal and external validation, while calibration was weaker for most plasma biomarkers. Five web applications (CogStrat) were developed using clinical data alone or combined with hippocampal volume, CSF tau/Aβ42, plasma neurofilament light chain, or FDG and florbetapir PET. These tools provide individualized risk group classifications, 5-year risk estimates, and 10-year cumulative incidence curves. CogStrat translates prognostic models into freely accessible, interactive tools that support risk stratification of cognitive impairment in cognitively normal older adults.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2371-2385"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148038842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-dependent association of uric acid levels with depressive symptoms in adults: NHANES 2007-2018.","authors":"Cong Yao, Guoshuai Luo, Meng Zhang, Yunsheng Fu, Xin Liu, Zonglin Li, Zipeng Chen, Jie Li","doi":"10.1007/s00702-026-03197-x","DOIUrl":"10.1007/s00702-026-03197-x","url":null,"abstract":"<p><p>Serum uric acid levels may influence depressive symptoms. Our study aimed to investigate the age-dependent association between serum uric acid levels and depressive symptoms in adults, using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Weighted multivariate logistic regression models were employed to assess the association between uric acid levels and depressive symptoms. A rolling window model (20-year window) was applied to explore age-related trends in odds ratios (ORs), leading to age stratification: < 40 years and ≥ 40 years. The ORs of uric acid in the two age groups were calculated using two different multinomial logistic regression models that adjusted for age, gender, race and no variables, respectively. Finally, we applied the Games-Howell test to compare the differences in bootstrap ORs between different uric acid groups. No significant association was found between uric acid and depressive symptoms in subjects aged below 40. Among subjects aged 40 and above, the moderate uric acid levels (315.2-374.7 µmol/L) were associated with lower odds of depressive symptoms (OR = 0.78, 95% CI 0.63-0.98, P < 0.05). After adjustment, the high uric acid levels (≥ 374.7 µmol/L) were associated with higher odds of depressive symptoms (OR = 1.31, 95% CI 1.04-1.67, P < 0.05). A trend of increasing ORs with higher uric acid levels was observed. High uric acid levels (≥ 374.7 µmol/L) were associated with increased odds of depressive symptoms in individuals aged ≥ 40 years.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2305-2315"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148274561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous whole retinal degeneration in aged Beclin1 heterozygous mice.","authors":"Francesca Biagioni, Maurizio Forte, Flavio di Nonno, Carla Letizia Busceti, Roberto Pinelli, Violet Vakunseh Bumah, Michela Ferrucci, Gloria Lazzeri, Sebastiano Sciarretta, Giacomo Frati, Francesco Fornai","doi":"10.1007/s00702-026-03166-4","DOIUrl":"10.1007/s00702-026-03166-4","url":null,"abstract":"<p><p>Retinal degenerative diseases range from rare inherited forms to common multifactorial disorders such as age-related macular degeneration, which is the leading cause of blindness in developed countries. Recent evidence identifies impaired autophagy as a key pathogenetic mechanism. In the disease process alterations of the outer retina start from the retinal pigment epithelium (RPE), to progress downstream in the inner retina leading to widespread whole retinal degeneration. Recent studies indicate that among autophagy-related proteins Beclin1 plays a relevant effect in sustaining retinal integrity, since it is induced by light exposure and it is placed at the intersection between mitophagy, lipophagy, and glycophagy, which are involved during retinal degeneration. The present study was carried out by profiting of BECN1 heterozygous aged mice (BECN+/-), where RT-PCR and western blotting analysis confirmed the loss of both the primary transcript (BECN1) and protein (Beclin1) in the whole retina. Multiple converging techniques indicate a marked degeneration of RPE and photoreceptor layer, where a dismantling of proteins forming tight junction was documented. Inner retinal degeneration was extended within outer and inner nuclear layer. In the inner retina the expression of the detrimental protein alpha synuclein was increased concomitantly with a defect of autophagy markers. The study indicates a seminal role of Beclin1 in maintaining retinal integrity and it defines the vulnerability of various retinal layers in the spreading of Beclin1-dependent retinal degeneration. The potential of increasing the expression of Beclin1 through photobiomodulation is discussed, since it supports retinal integrity when amber/red light-induced stimulation occurs.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2395-2416"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147849115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Higher serum uric acid associates with better cognitive performance and survival in Caribbean parkinsonism.","authors":"Tanicia Mameri, Regine Edragas, Annick Chavonnet, Benoit Tressieres, Loic Dragin, Angela Lackmy, Véronique Pelonde-Erimee, Stanie Gaete, Regine Hierso, Pierre Pouget, Emmanuel Roze, Patrick Pierre Michel, Annie Lannuzel","doi":"10.1007/s00702-026-03229-6","DOIUrl":"10.1007/s00702-026-03229-6","url":null,"abstract":"<p><p>Reduced serum uric acid (UA) has been identified as a risk factor for Parkinson's disease (PD), prompting investigation into its relevance in atypical Parkinsonism (AP). Serum UA levels were measured in a prospective Caribbean cohort (ClinicalTrials.gov: NCT03368300, 03/08/2012) comprising patients with PD (n = 90), AP (n = 167), and healthy controls (n = 124), and associations with clinical variables were assessed. Serum UA levels were significantly lower in patients with PD and AP than in controls (p = 0.004). Across the entire cohort, patients with low UA levels had higher adjusted odds of poor neuropsychological performance, defined as Mini-Mental State Examination score < 24 (OR = 4.7), Mattis Dementia Rating Scale score < 137 (OR = 2.97), and Frontal Assessment Battery score < 13 (OR = 2.79). Survival analyses also revealed significant differences across sex-specific UA tertiles (p = 0.044). In AP, low and intermediate UA levels were associated with higher mortality (p = 0.035). Lower serum UA levels, however, were not associated with overall disease severity or functional dependence. Our findings provide further evidence supporting the relevance of UA to the pathogenesis of neurodegenerative parkinsonism. They may also offer opportunities for risk stratification and the investigation of UA-related interventions in patients with Caribbean parkinsonism.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2661-2670"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148883398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polygenic risk meets early trauma: toward a neuropsychodevelopmental model of schizophrenia.","authors":"Antonio Del Casale, Paolo Girardi, Jan Francesco Arena, Claudio Cantelmi, Martina Nicole Modesti, Liliana Bronzatti, Ludovica Zanini, Giorgio Veneziani, Emanuele Giraldi, Sofia Mazzani, Maurizio Simmaco, Carlo Lai, Grazia Spitoni, Giacomo Ciocca","doi":"10.1007/s00702-026-03263-4","DOIUrl":"10.1007/s00702-026-03263-4","url":null,"abstract":"<p><p>Advances in psychiatric genetics have substantially reshaped current models of schizophrenia-spectrum disorders, shifting the focus from single risk factors to polygenic liability and its interaction with environmental adversity. Polygenic risk scores (PRS) provide a quantitative index of genetic vulnerability; however, how this liability interfaces with early-life stress-particularly childhood trauma-across neurodevelopment remains insufficiently conceptualized. Accumulating evidence indicates that the interplay between polygenic risk and childhood trauma influences not only the likelihood of psychosis onset but also the emergence of specific symptom dimensions during clinical high-risk states and early stages of illness. Yet, existing theoretical frameworks tend to consider genetic predisposition and environmental exposure as parallel or additive processes, offering limited insight into their developmental convergence. In this Perspective, we examine current neurodevelopmental models of schizophrenia and integrate them within a unified framework, proposing that polygenic liability, environmental exposures (including early trauma), and psychological processes interact dynamically and bidirectionally across sensitive developmental windows, shaping distinct neuropsychodevelopmental trajectories. Integrating polygenic, environmental, and developmental domains within a unified neuropsychodevelopmental framework may help explain clinical heterogeneity, with important implications for early identification, risk stratification, and personalized preventive strategies.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2757-2768"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and state-dependent patterns of non-motor fluctuations in Parkinson's disease.","authors":"Shweta Prasad, Tarunya Nagaraj, Shubha Gs Bhat, Mahima Bhardwaj, Shyam Sundar Aramugham, Keshav J Kumar, Pooja Mailankody, Rohan R Mahale, Vikram V Holla, Nitish Kamble, Ravi Yadav, Pramod Kumar Pal","doi":"10.1007/s00702-026-03222-z","DOIUrl":"10.1007/s00702-026-03222-z","url":null,"abstract":"<p><p>Parkinson's disease (PD) has non-motor symptoms (NMS), many of which fluctuate with motor states. These non-motor fluctuations (NMF) can remain under-characterized, particularly in relation to age at onset. Early-onset PD (EOPD) and late-onset PD (LOPD) may exhibit distinct fluctuation patterns, potentially reflecting differences in neurochemical vulnerability. To characterize the prevalence, distribution, and state dependence of NMF in a large PD cohort using the Non-Motor Fluctuation Assessment (NoMoFA) questionnaire, and to compare NMF profiles between EOPD and LOPD. In this study 484 patients meeting MDS-PD criteria were recruited at a tertiary centre and NMS/NMF were collected using NoMoFA. Symptoms were classified as static or fluctuating, with OFF state, ON state, or mixed-state worsening. Group comparisons used chi-square tests for categorical variables and independent-sample t-tests for continuous variables and multivariate binary logistic regression was performed to identify independent predictors of NMF. A substantial proportion of NMS demonstrated fluctuation. Emotional and sensory symptoms showed the highest fluctuating burden, with OFF-state worsening predominating. Pain fluctuated in 44.5% of symptomatic patients, almost entirely during OFF. Excessive daytime sleepiness showed more ON-state worsening. EOPD exhibited significantly higher fluctuating emotional symptoms whereas LOPD showed greater prevalence of static autonomic symptoms. NMF presence was associated with significantly higher Parkinson's Disease Questionnaire-39 (PDQ-39) scores across multiple domains, particularly mobility, activities of daily living (ADL), emotional well-being, and bodily discomfort (p < 0.001). NMF are common, clinically significant, and predominantly related to the OFF state. Distinct NMF patterns in EOPD vs. LOPD suggest differing pathophysiological contributions. Female gender and dyskinesia were independent predictors of NMF after multivariate adjustment.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2609-2621"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148371738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}