Neurodegenerative disease management最新文献

This case report describes a 54-year-old Chinese woman with progressive gait instability, speech slowing, and cerebellar ataxia. Initial symptoms included mild bradykinesia and frequent backward falls. Neurological evaluation revealed supranuclear gaze palsy, hyporeflexia, and cerebellar dysfunction (SARA 26/40). Differential diagnoses included MSA, SCA, and PD. Genetic testing excluded SCA, while advanced imaging ruled out other disorders. The patient met criteria for probable PSP-C, a rare PSP subtype marked by cerebellar ataxia. [¹⁸F]PM-PBB3 tau PET imaging demonstrated abnormal tau accumulation in the striatum, thalamus, midbrain, and pons, consistent with PSP-C neuropathology. This case underscores the diagnostic utility of tau PET in distinguishing PSP-C from overlapping conditions and provides novel imaging evidence in an Asian cohort. Findings highlight the potential of noninvasive tau-targeted imaging for early detection and management of PSP-C.

Background and objectives: Gut microbiota dysbiosis is increasingly implicated in Parkinson's disease (PD). This study aimed to find gut microbiota diversity and composition of PD patients in Central Kerala population, India.

Methods: 16 PD patients were enrolled and their spouse formed the controls. Fecal Microbiome analysis was performed by 16S rRNA amplicon sequencing.

Results: Seven microbial species significantly contributed to the differences in beta diversity between the PD and control groups (p = 0.007). On network analysis Bifidobacterium longum, Bacteroides fragilis, Blautia obeum and Roseburia faecis represented the PD group communities and Ruminococcus bromii and Ruminococcus gnavus represented the controls. Faecalibacterium prausnitzii and Ruminococcus gnavus enhanced centrality in the spouse control network and Bifidobacterium longum, Eubacterium biforme, and Roseburia faecis in PD group.

Conclusions: This study offers initial evidence for identifying PD associated gut microbiome alterations in the Kerala population to be further explored with larger and more detailed longitudinal study.

Background: Routine clinical evaluations offer limited insight into daily variability and disease progression in Parkinson's disease (PD). While wearable devices are increasingly used to improve patient monitoring, evidence of their effectiveness remains scarce.

Objective: To assess the efficacy of integrating a telemonitoring system into standard clinical procedures, highlighting its role in enabling efficient, patient-centered treatment adjustments.

Methods: Thirty-five PD patients were monitored for 6 months using a telemonitoring device alongside standard care. Disease progression was assessed via MDS-UPDRS part III (UPDRS-p3) and device-reported outcomes (dUPDRS) at baseline and follow-up. Physicians provided feedback on telemedicine utility.

Results: UPDRS-p3 scores improved by 1.9-5.63 points. Changes in UPDRS-p3 strongly correlated with dUPDRS (r = 0.82). Sixty-two percent of patients had treatment modifications, 36% of which occurred remotely.

Conclusion: Telemonitoring supported clinical decisions, detected subtle symptom changes, and offered valuable insights for improving motor symptoms and patient management.

Background: Inflammation is known in atypical parkinsonism (AP), but the role of autoimmunity is unclear. This study evaluates immune system modifications suggesting autoimmunity in AP.

Methods: Included patients with AP diagnosed at Amrita Institute of Medical Sciences, Kochi (December 2018-May 2019), and age- and sex-matched controls. Fifteen immune parameters, including T regulatory cells, RORγt, and cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IL-21, IL-22, IL-23, TNF, IFN-γ, GM-CSF, NF-κB, TGF-β), were assessed in peripheral blood (flow cytometry and ELISA).

Results: Twenty-six cases (mean age 67.8 ± 7.5 years; 16 males) and 15 controls (mean age 68.1 ± 3.5 years; 10 males) studied. Diagnoses included progressive supranuclear palsy (n = 15), multiple system atrophy (n = 1), frontotemporal dementia with parkinsonism (n = 2), and unspecified AP (n = 8). AP cases had significantly higher RORγt (p = 0.041), IL-6 (p = 0.004), TNF (p = 0.020), IL-10 (p = 0.027), and IL-4 (p = 0.048).

Conclusions: Elevated RORγt and cytokines suggest immune dysregulation and possible autoimmune mechanisms in AP, warranting further investigation.

Background: Inflammation is implicated in neurodegeneration, but the causal link between multiple sclerosis and Alzheimer's disease remains unclear.

Objective: To investigate the genetic relationship between MS and AD using Mendelian Randomization and assess downstream molecular effects.

Methods: Two-sample MR was conducted using GWAS summary statistics, with IVW and MR Egger methods. Sensitivity analyses assessed pleiotropy and heterogeneity. eQTL and KEGG pathway analyses explored gene expression and functional relevance.

Results: Sixty-four SNPs from European MS GWAS were selected for MR analysis; an African American dataset showed no significant SNPs. IVW and MR-Egger indicated a positive causal association between MS and AD (p < 0.05). Pleiotropy (Egger β = -0.017, p = 0.002) was addressed using robust methods. eQTL analysis identified 41 genes, with KEGG enrichment implicating Th1/Th2 and Th17 differentiation pathways.

Conclusion: MS may increase AD risk via shared T-cell - mediated immunogenetic mechanisms.

Aim: To evaluate the survival rates in well-characterized cohorts of frontotemporal dementia (FTD) subtypes - behavioral variant (bvFTD), progressive nonfluent aphasia (PNFA), and semantic dementia (SD) - and both typical (amnestic) and atypical (aphasic: logopenic progressive aphasia [LPA]) presentations of Alzheimer's disease (AD).

Patients & methods: Three hundred and twenty-one participants (54 bvFTD, 26 PNFA, 22 SD, 20 LPA, 32 AD, 167 controls) were recruited. Patients underwent a comprehensive baseline assessment and annual reviews. Survival data were analyzed using Kaplan-Meier curves and Cox proportional hazard models.

Results: Median survival from symptom onset was longest in SD (11.9 years) and shortest in LPA (7 years). Median survival for the bvFTD, PNFA, and AD groups was 8.7, 8.6, and 10 years, respectively. SD survival was significantly longer than PNFA and AD. Female sex was associated with shorter survival in LPA. Shorter symptom duration at baseline assessment was related to shorter survival in bvFTD, SD, LPA, and AD. Lower overall cognition in bvFTD, LPA, and AD, and worse functional outcomes in SD and AD at baseline were associated with shorter survival.

Conclusions: Our findings demonstrate distinct survival patterns across FTD and AD subtypes. Demographic and presenting clinical features provide valuable prognostic insights for survival.

L-3,4-dihydroxyphenylalanine (Levodopa)-induced dyskinesia remains a condition for which there are few therapeutic options available. Fortunately, the past 5 years have seen the completion of several clinical trials, some of which yielded positive and encouraging results. Here, we performed a review of the clinical trials that were completed or for which outcomes were disclosed within the past 5 years. Promising results were obtained in Phase II trials with the serotonin type 1A (5-HT_1A) agonist befiradol, the dopamine D₃ receptor antagonist mesdopetam and the phosphodiesterase inhibitor CPL500036. In contrast, the metabotropic glutamate 4 (mGlu₄) receptor negative allosteric modulator foliglurax and JM-010 (a combination of the 5-HT_1A partial agonist buspirone and the and the 5-HT type 1B and 1D [5-HT_1B/1D] agonist zolmitriptan) did not meet their endpoints in Phase II studies. Lastly, robot-assisted Repetitive Transcranial Magnetic Stimulation (rTMS) of the pre-supplementary motor area may be a promising non-pharmacological approach to alleviate dyskinesia.

Parkinson's disease (PD) is a progressive neurodegenerative disorder marked by motor dysfunction and complex gait abnormalities. Traditional linear methods often fail to capture the intricate movement patterns in PD. This review highlights Multiscale Entropy (MSE) as a promising tool for assessing gait dynamics, offering deeper insights into movement variability across multiple temporal scales. MSE distinguishes healthy and pathological gait patterns, enhancing early diagnosis and disease monitoring. Advances in wearable sensors, artificial intelligence, and machine learning have boosted MSE's clinical relevance by enabling real-time, personalized gait assessments. Despite these benefits, MSE faces challenges such as computational demands and the need for high-resolution data. Addressing these limitations through large-scale studies, standardized protocols, and integration of emerging technologies may support broader clinical adoption and the development of a robust normative database.

Background: The peak prevalence of multiple sclerosis (MS) is shifting to older patients. Using real-world data, we describe outcomes among older (≥60 years) and younger patients treated with interferon beta-1a or no disease-modifying therapy (no-DMT).

Methods: Assessments over 24 months included annualized relapse rates (ARRs), patient-reported disability outcomes, and MS Performance Test (MSPT) outcomes.

Results: The study included 767 interferon-treated and 2783 no-DMT patients. ARR over 24 months was lower for the older and younger interferon-treated patients than the no-DMT patients. Mean change in Patient-Determined Disease Steps (PDDS) from baseline-24 months was -0.13 (1.08) in older interferon-treated patients vs 0.20 (1.30) in older no-DMT patients.

Conclusion: Over 24 months ARR remained low and disability progression was stable for interferon-treated patients aged ≥ 60 years.

Aims: Understanding the holistic experience of patients with early Alzheimer's disease (AD) and their care partners is important to identify unmet needs. This study aimed to describe and compare patient-care partner dyad experiences and perspectives in early AD.

Patients & methods: Experiences of patients and their care partners (dyads) were explored using a survey, qualitative interviews, and social media listening. Each dyad completed a 25-minute quantitative online survey exploring their perceptions of symptoms, comorbidity impact, financial burden, and preferred treatment characteristics. Data were analyzed descriptively and comparatively.

Results: 150 patient-care partner dyads completed the survey. Patients and care partners frequently reported memory-related issues and cognitive challenges (68% and 77%, respectively); approximately 19% of responses were discordant, with patients often under-reporting symptoms. Managing comorbidities worsened overall well-being of patients (41%) and care partners (40%). Treatments slowing AD progression (patients: 99%; care partners: 96%) and improving symptoms (patients: 95%; care partners: 93%) were important. Approximately 26% of respondents experienced significant negative financial impacts.

Conclusions: Patients and care partners perceived early AD impacts similarly whereas some symptoms were perceived differently. There was a shared desire for disease-modifying treatments. Limited financial impact may reflect preserved functionality and limited use of disease-modifying treatments.