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

{"title":"Update on sleep disorders in advanced Parkinson's disease: a narrative review.","authors":"Emmanuel Roze, Monika Rudzinska, Tove Henriksen, Eero Pekkonen, Michal Minar, Artur Druzdz, Bo Biering-Sørensen, Anders Johansson, Smaranda Leu-Semenescu","doi":"10.1007/s00702-025-02994-0","DOIUrl":"https://doi.org/10.1007/s00702-025-02994-0","url":null,"abstract":"<p><p>Multiple types of sleep disorders are encountered in patients with Parkinson's disease (PD) and are often underreported and underdiagnosed. They include circadian disorders, insomnia, excessive daytime sleepiness, rapid-eye-movement-sleep behavioral disorder, restless legs syndrome, and obstructive sleep apnea. The prevalence of sleep problems increases early in the disease course, and sleep quality deteriorates overall as patients age and the disease progresses. At advanced stages of PD, there is a reciprocal link between sleep problems and PD manifestations: sleep problems tend to exacerbate motor and non-motor symptoms, while worsening of motor and non-motor conditions have a detrimental effect on sleep quality. As the disease advances, sleep disorders have a growing negative influence on the quality of life of both patients and family caregivers. The causes of sleep disorders in this setting are neurodegeneration of key brain structures involved in sleep, motor and non-motor manifestations interfering with sleep, and drugs interfering with sleep. Treatment can include optimisation of antiparkinsonian treatment, reduction or removal of drugs interfering with sleep, treatment of non-motor manifestations interfering with sleep, pharmacological treatment of specific sleep disorders, and non-pharmacological approaches. Efforts should be made to raise awareness among patients, families, students, physicians, charities, funders, and policy makers regarding the prevalence and consequences of sleep disorders in advanced PD.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763010","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":"Far from being the end of the road: taking a closer look at neuropalliative care in Parkinson's disease.","authors":"Manon Auffret, Fran Borovecki, Beatrice Heim, Wolfgang H Jost, Per Odin, Fabrizio Stocchi, Maja Trost, Marc Vérin","doi":"10.1007/s00702-025-02989-x","DOIUrl":"https://doi.org/10.1007/s00702-025-02989-x","url":null,"abstract":"<p><p>Parkinson's disease (PD) is now recognized as a multisystem, heterogeneous neurodegenerative disease with fluctuating trajectories and complex symptom profiles. Despite therapeutic advances, many patients (particularly women and those in late stages) and their caregivers face substantial unmet needs across physical, psychological, social, and spiritual domains, which highlight the need for a more integrative care model. Palliative care, defined as holistic, person-centered care for individuals with life-limiting illnesses, is increasingly recognized as particularly relevant in PD, from early to terminal stages. However, its implementation in neurology remains limited, notably due to persistent misconceptions, and delayed or absent referrals. This narrative review therefore aims to equip PD care teams with a clearer understanding of palliative care principles and their applicability to PD, by synthesizing emerging evidence in neuropalliative care, and providing practical recommendations for integration into routine neurological practice. Building on the specificities of quality of care for chronic conditions, optimal neuropalliative care in PD involves regular (re)assessment of symptoms and priorities, effective management of the chronic-palliative interface, good communication, continuity of care (including neurological care until the end of life), and a multidisciplinary network of professionals working both in the community and in specialized clinics, while leaving room for the involvement of caregivers. Far from being \"the end of the road\", neuropalliative care is a strategic and compassionate response to the evolving complexity of PD, which ultimately enhances quality of life, supports families, and reinforces the neurologist's pivotal role in longitudinal, person-centered care.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746864","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":"Assessing the effects of methylphenidate in proliferation and Wnt activity of neuronal stem cells from attention deficit/hyperactivity disorder patients.","authors":"Cristine Marie Yde Ohki, Natalie Monet Walter, Lukasz Smigielski, Audrey Bender, Michelle Rickli, Susanne Walitza, Edna Grünblatt","doi":"10.1007/s00702-025-02988-y","DOIUrl":"https://doi.org/10.1007/s00702-025-02988-y","url":null,"abstract":"<p><p>As the most common neurodevelopmental and mental disorder around the world, attention-deficit/hyperactivity disorder (ADHD) affects primarily children and adolescents. Both genetic (polygenicity) and environmental variables interplay in the etiology of this disorder. The Wnt signaling pathway, which regulates proliferation and differentiation during neurodevelopment, has been implicated in ADHD. Clinically, individuals with ADHD may exhibit delays in structural and functional brain development. Available evidence suggests that methylphenidate (MPH) treatment can potentially improve these delays. However, the molecular and cellular mechanisms underlying ADHD and the therapeutic targets of MPH are not yet completely elucidated. In a pilot investigation, the proliferation of neural stem cells (NSCs) derived from induced pluripotent stem cells (iPSCs) was significantly lowered in ADHD male patients. Yet, we did not observe any variations in proliferation rates during the iPSC stage. To extend the earlier results, we increased the sample size to include females, explored whether MPH may improve NSC proliferation in ADHD and clarified the role of the Wnt pathway. To do so, iPSC and NSC proliferation from five ADHD patients and five controls was assessed. The results corroborated our previous findings of decreased proliferation in ADHD NSCs. Conversely, ADHD NSC proliferation was modestly regulated by MPH treatment at 10 nM, which also showed modulatory effects on Wnt signaling in this group. Interestingly, no increase in proliferation was seen when DKK1 blocked Wnt signaling before MPH treatment. These findings suggest MPH regulates the canonical Wnt pathway and may partially explain ADHD-related neurodevelopmental abnormalities and MPH-specific benefits.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736638","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":"Silent destruction: hidden muscle wasting and body decline in early Huntington's disease.","authors":"Marina Peball, Pia Schörghuber, Federico Carbone, Anne Zinganell, Franziska Di Pauli, Katarína Schwarzová, Atbin Djamshidian, Klaus Seppi, Beatrice Heim","doi":"10.1007/s00702-025-02991-3","DOIUrl":"https://doi.org/10.1007/s00702-025-02991-3","url":null,"abstract":"<p><p>Huntington´s Disease (HD) is an autosomal dominant, neurodegenerative disorder with characteristic motor, behavioural, and cognitive impairment. Mutant Huntingtin may also affect peripheral tissue. We aimed to assess skeletal muscle (SMM) and fat mass, sarcopenia (EWGSOP2), and malnutrition in HD patients in early disease stages compared to age- and sex-matched healthy subjects. Body composition was evaluated by bioelectrical impedance analysis. The Unified HD Rating Scale and cognitive assessments were used for clinical characterization. Twenty early-stage HD patients (45% females) with a median age of 57 years, body mass index of 22 kg/m², Total Motor Score of 17 points, and Total Functional Capacity of 10 points were included consecutively and prospectively. Confirmed sarcopenia (15%, n = 3) was uncommon. Appendicular SMM index was reduced in 60% (n = 12) and body fat mass in 35% (n = 7). SMM reduction was significantly associated with low weight (p = 0.049) and body fat (p = 0.048). Patients in disease-stage2 (n = 11) had a lower weight (p = 0.009) and body fat (p = 0.008) than patients in disease-stage1 (n = 9; i.e., patients without functional decline). Weight was also lower (p = 0.011) when compared to 20 healthy controls (45% females; median age 56 years). Fifty-five % of HD patients were at risk for malnutrition or malnourished (Mini Nutritional Assessment). The latter correlated with weight (r_s = 0.724, p < 0.001), SMM (r_s = 0.473, p = 0.035), body fat mass (r_s = 0.611, p = 0.004), motor symptoms (r_s = - 0.519, p = 0.019), independence (r_s = 0.450, p = 0.046), and executive function (r_s = 0.526, p = 0.017). Reduction of muscle or fat mass and malnutrition are common even in early-stage HD, which may contribute to progressive wasting and dependence.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736640","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":"Motor and non-motor fluctuations in Parkinson's disease: the knowns and unknowns of current therapeutic approaches.","authors":"Martin Regensburger, Ilona Csoti, Wolfgang H Jost, Zacharias Kohl, Stefan Lorenzl, David J Pedrosa, Paul Lingor","doi":"10.1007/s00702-025-02990-4","DOIUrl":"https://doi.org/10.1007/s00702-025-02990-4","url":null,"abstract":"<p><p>Neurodegeneration in Parkinson's disease is chronically progressive, and no disease-modifying therapies have been approved so far. Fluctuations emerge in eventually all people with Parkinson's disease, and may lead to a high burden of motor and non-motor disability and significantly impair participation if they are inadequately treated. In recent years, the range of therapeutic options has expanded considerably. While different types of oral dopaminergic substances are initially applied to control fluctuations, additional routes of administration now encompass sublingual, inhalative, subcutaneous and transdermal applications. Different choices exist for on-demand and continuous pump therapies, as well as for deep brain stimulation. In this narrative review, we summarize the state of the art in the identification and treatment of motor and non-motor fluctuations in Parkinson's disease. Moreover, we discuss practical aspects of managing fluctuations, address yet unresolved questions and we offer insights into upcoming clinical developments.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736639","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":"Declining incidence of Parkinson's disease in Israel (2002-2021).","authors":"Yacov Balash, Tamar Zohar, Ronit Gilad, Anda Eilam, Amos D Korczyn","doi":"10.1007/s00702-025-02984-2","DOIUrl":"https://doi.org/10.1007/s00702-025-02984-2","url":null,"abstract":"<p><p>The results of investigations of the trends of the incidence of Parkinson's disease (PD) over time in numerous developed countries showed that aging and increasing life expectancy are leading to an increase in both. We investigated the crude and age-adjusted incidence rates (AAIRs) of PD based upon registry data of Israel's largest health maintenance organization between 2002 and 2021 according to joinpoint regression. We applied an age-period analysis to further identify patterns of AAIR changes, and calculated longitudinal age curves of PD rates (\"local drift\") as well as annual change of the expected age-specific and expected age-adjusted AAIR (\"net drift\"). The overall AAIR of PD declined from 57 ± 1.0 to 20.3 ± 0.5 per 100,000 over 20 years, representing a 2.8-fold decrease. The PD incidence decreased more rapidly among females (average annual percent changes [AAPC] - 5.3%, 95% confidence interval [CI] - 6.0-4.6, p < 0.001) than among males (AAPC - 4.5, 95%CI - 5.3-3.7, p < 0.001). AAIRs peaked at 209.9 (CI: 193.0-228.5) per 100,000 at a median age of 77.5 vs. 374.9 (CI: 350.9-400.5) years in females and at a median age of 82.5 years in males. AAIRs gradually declined in males to 63.3 (CI: 52.2-84.1) per 100,000 and in females to 29.7 (CI: 21.4-41.1) per 100,000 for the 97.5-year-old group in both sexes. This first assessment of the trends of the incidence of PD in Israel documented its progressive decline from 2002 to 2021, especially among the very elderly. This decline may reflect refined diagnostic capabilities and enhanced health, quality of life and environmental conditions in Israel.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693099","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":"Association of blood pressure variability with white matter hyperintensities and nigrostriatal dopaminergic deficits in drug-naïve Parkinson's disease.","authors":"Hiromasa Matsuno, Tadashi Umehara, Masahiro Mimori, Masakazu Ozawa, Tomotaka Shiraishi, Asako Onda, Keiko Bono, Shusaku Omoto, Renpei Sengoku, Hidetomo Murakami, Yasuyuki Iguchi","doi":"10.1007/s00702-025-02985-1","DOIUrl":"https://doi.org/10.1007/s00702-025-02985-1","url":null,"abstract":"<p><p>Blood pressure variability, white matter brain lesions and degeneration of nigrostriatal dopaminergic neurons may be associated with each other in patients with Parkinson's disease (PD). We examined the coefficient of variation of systolic blood pressure (CV-sBP) in 122 drug-naïve patients with newly diagnosed PD. The association of CV-sBP with degree of white matter hyperintensities and striatal specific binding ratio (SBR) of ¹²³I-2 carbomethoxy-3-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (¹²³I-FP-CIT) were examined taking cardiovascular risk factors into account. The results showed that patients with higher CV-sBP were older (r = 0.362, p < 0.001) and had severer periventricular hyperintensities (PVH) (r = 0.261, p = 0.002), deep and subcortical white matter hyperintensities (DSWMH) (r = 0.237, p = 0.004) and lower striatal SBR (right SBR: r = - 0.269, p = 0.002, left SBR: r = - 0.341, p < 0.001). Patients with severer PVH or DSWMH had lower striatal SBR (PVH: r = - 0.317, p < 0.001, DSWMH: r = - 0.350, p < 0.001). CV-sBP was significantly associated with left striatal SBR (β =-0.264, p = 0.008), especially left caudate SBR (β = - 0.181, p = 0.044) after controlling for age, sex, motor severity, hypertension, diabetes, and DSWMH grade. In conclusion, higher blood pressure variability was associated with greater dopaminergic degeneration in the left striatum, independently of white matter hyperintensity grade. Whether this association reflects dopaminergic neuronal loss or structural alterations in the striatum remains unclear.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677187","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 link between Wnt-related, stress-related, and circadian genes in the dermal fibroblasts of individuals with attention-deficit hyperactivity disorder.","authors":"Denise Palm, Lukasz Smigielski, Adriana Uzoni, Oliver Tucha, Johannes Thome, Edna Grünblatt","doi":"10.1007/s00702-025-02986-0","DOIUrl":"https://doi.org/10.1007/s00702-025-02986-0","url":null,"abstract":"<p><p>Attention-deficit/hyperactivity disorder (ADHD) has been associated with circadian rhythm disturbances, altered stress responses, and, in neural stem cells from ADHD patients, aberrant Wnt signaling. However, little is known about how these molecular pathways interact. This study aimed to investigate rhythmic expression of circadian, Wnt signaling, and stress-related genes in the context of ADHD. Human dermal fibroblasts were obtained via skin biopsy from participants diagnosed with ADHD (n = 13) and healthy controls (n = 13). Fibroblast cultures were synchronized using dexamethasone, with samples collected every 4 h over 28 h. Gene expression of Wnt signaling, stress-related, and circadian clock genes was quantified by qRT-PCR. Harmonic regression was applied to estimate rhythmicity (amplitude and phase), followed by mixed-effects modeling and likelihood ratio tests to assess between-group differences and gene-gene associations. Circular statistics (Rayleigh test, Watson two-sample test, circular correlations) were employed to test the uniformity and synchronicity of phase distributions. BMAL1, CRY1, PER2, PER3, and DKK1 exhibited significant rhythmicity within each group. DKK3 was rhythmic only in the ADHD group. Although between-group differences did not reach statistical significance, BMAL1 and CRY1 expression peaked later, while PER2 and PER3 expression peaked earlier in the ADHD group. Depending on data filtering, gene-gene rhythmicity associations included CRY1-SIRT1, PER3-FOXO1, and CLOCK-CTNNB1 in ADHD subjects, as well as CLOCK-DKK1 (ADHD) and BMAL1-DKK1 in controls. The phase and amplitude of core clock genes were correlated with donors' ADHD symptoms and subjective sleep measures. Our data indicate ADHD is associated with subtly altered circadian gene expression and distinct integration of Wnt signaling and stress-related pathways, supporting the hypothesis of broader molecular dysregulation underlying ADHD.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677189","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":"Correction: Neural autoantibodies in psychiatric disorders are associated with antibodies against viral pathogens: a retrospective study of 619 patients.","authors":"Niels Hansen, Vincent Buschatzky, Anne Katharina Bastin, Kristin Rentzsch, Bianca Teegen, Daniel Luedecke, Thomas Skripuletz, Hannah Benedictine Maier, Stefan Bleich, Jürgen Gallinat, Hermann Esselmann, Ildiko Rita Dunay, Inga Zerr, Dirk Fitzner, Jens Wiltfang, Alexandra Neyazi, Björn Hendrik Schott, Berend Malchow","doi":"10.1007/s00702-025-02973-5","DOIUrl":"https://doi.org/10.1007/s00702-025-02973-5","url":null,"abstract":"","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677188","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":"Cognitive disorders and parkinson's disease: a literature review.","authors":"Roland Dominic G Jamora, Liamuel Giancarlo V Untalan, Donna Mae Lyn B Santiago, Louis C S Tan","doi":"10.1007/s00702-025-02983-3","DOIUrl":"https://doi.org/10.1007/s00702-025-02983-3","url":null,"abstract":"<p><p>Parkinson's Disease (PD) is a movement disorder characterized by tremors, rigidity, and bradykinesia, accompanied by several non-motor symptoms, with cognitive impairment as one of the most debilitating. This narrative review of literature aims to provide a general overview on the defining features, pathologic changes, and management principles of cognitive changes in PD. A literature review was conducted by searching the terms \"Cognition\" OR \"Cognitive Decline\", AND \"Parkinson's Disease\" in PubMed, Scopus, and Google Scholar. Mild cognitive impairment (PD-MCI) and dementia (PDD) have been well-defined with consensus criteria. Recent researches have focused on pathophysiologic changes, identifying patterns of atrophy, as well as corresponding neurochemical insults. These have been primarily targeted in the existing pharmacologic literature, with evidence for non-pharmacologic therapies still lacking. Cognitive changes in PD range from a spectrum of mild cognitive impairment (PD-MCI) to dementia (PDD). Evidence exists for clinical and pathologic mechanisms which guide current and future therapeutic principles. Current trends of research are focused on the potential of discovering preventive therapies strengthens the need for more high-level evidence in the future.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661739","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}