Neurodegenerative disease management最新文献

Neurodevelopmental disorders (NDDs), including autism spectrum disorder, attention deficit/hyperactivity disorder, intellectual disability, and Down syndrome, are increasingly examined through the lens of aging. Emerging evidence indicates that individuals with NDDs may exhibit accelerated or atypical brain aging, characterized by cognitive decline and increased vulnerability to neurodegenerative conditions such as Alzheimer's and Parkinson's disease. This narrative review synthesizes current findings on biological mechanisms implicated in altered aging trajectories, with emphasis on oxidative stress, chronic neuroinflammation, mitochondrial dysfunction, and cellular senescence. These processes, detectable from early development, mirror pathways involved in neurodegeneration, suggesting shared molecular cascades that increase susceptibility to early aging. Biomarker studies report telomere shortening, elevated plasma glial fibrillary acidic protein and neurofilament light chain levels, and deviations in neuroimaging-derived brain age, supporting the hypothesis of altered biological aging in NDDs. However, the limited number of longitudinal lifespan studies, along with marked heterogeneity in etiology, clinical profiles, and comorbidities, constrains causal inference. Psychosocial and environmental factors, including chronic stress, social exclusion, medical comorbidities, and lifestyle influences, further shape aging outcomes. Integrating biological, behavioral, and environmental markers is essential to advance monitoring and inform early interventions aimed at promoting healthier cognitive and functional aging in neurodivergent populations.

Along with bradykinesia and rigidity, tremor is one of the cardinal motor symptoms of Parkinson's disease (PD), often the first symptom to be noticed by the patient and their relatives. While bradykinesia and rigidity usually respond to dopaminergic therapies, tremor is often refractory to these medications and can cause significant disability in many patients. This variability of response appears to be related to different mechanisms/neurochemical abnormalities underlying the occurrence of tremor in PD patients.Here, we will discuss types of tremors in PD, the current understanding of the neurochemistry underlying Parkinsonian tremor, as possible targets for treatment, and the role of imaging and wearable devices to improve tremor management in these patients. We will summarize pharmacological strategies and more complex approaches, such as Deep Brain Stimulation and Magnetic Resonance guided Focussed Ultrasound, currently used in the management of PD patients with tremor. The role of non-pharmacological strategies will also be appraised.

Aim: The aim of this manuscript was to investigate possible handwriting alterations focusing on micrographia in PD patients with STN-DBS in distinct stimulation conditions.

Methods: All consecutive PD patients with STN-DBS therapy who visited our movement disorder center between October 2023 and December 2023 and agreed to participate in the study were enrolled. Extensive clinical assessments including various scales were performed. The MDS-UPDRS-III-stimulation-'off' and 'on' scores were evaluated. The handwriting parameters including letter area, writing time and pressure were measured on a digital graphic tablet using an electronic pen. In addition to these parameters, indices related to micrographia were measured under four stimulation conditions (bilateral, left, right, no stimulation).

Results: Overall, we included 20 patients with a mean age of 56.7 ± 11.4 years (F/M = 7/13). The comparisons of the handwriting parameters did not reveal any significant differences between the distinct stimulation conditions. Writing duration showed strong correlations with the HAM-A score (CC = 0.662, p = 0.007) and the HDRS score (CC = 0.642, p = 0.005).

Conclusion: No stimulation-related dynamic changes were observed in handwriting kinematics in patients with STN-DBS. These findings might give perspectives regarding the pathophysiology of micrographia in PD as well as mechanisms underlying the efficacy of STN-DBS.

Aim: This systematic review study aimed to evaluate the impact of TES on cognitive dysfunction in MS patients, aiming to consolidate current knowledge and explore its clinical applicability.

Methods: A PRISMA-compliant search of MEDLINE, Scopus, and EMBASE identified randomized controlled trials (RCTs) and quasi-experimental studies assessing TES's impact on cognitive outcomes in MS. Data from nine studies were pooled using random-effects models, with subgroup analyses by stimulation type.

Results: Meta-analysis revealed a small-to-moderate pooled effect of TES on cognitive function (standardized mean difference [SMD] = 0.62, 95% CI: 0.36-0.88, p < 0.001), though substantial heterogeneity was observed (I² = 87.82%). Subgroup analysis showed tDCS improved cognitive outcomes (SMD = 0.32, p = 0.04), while tACS demonstrated a larger but non-significant effect (SMD = 1.39, p = 0.16). TES was generally safe, with transient side effects (e.g. scalp discomfort) reported.

Conclusion: TES shows promise as an effective and safe intervention for cognitive dysfunction in MS patients. While improvements were observed in various cognitive domains, outcome variability underscores the need for further research to refine stimulation protocols.

Aim: To examine the longitudinal loss of independence (LOI) in Parkinson disease (PD) and introduce event visualization as a research tool.

Methods: Early-stage PD patients seen by a movement disorders specialist from 2003-2020 were included. LOI, defined as needing help with activities of daily living (ADLs), was assessed using the modified Older Americans Resources and Services Daily Function Questionnaire. EventFlow software visualized LOI patterns.

Results: The cohort included 296 patients (mean age 60.8; 61% male; 94% Hoehn & Yahr stages 1-2). At baseline, 91% were independent. LOI occurred in 133 patients for ≥ 1 ADL, and in 95 patients for ≥ 3 ADLs. Housework was the most frequent first ADL needing help (58 of 133), with a mean onset of 4.6 years. Among those with LOI, 57 (43%) regained independence at least once.

Conclusion: LOI in PD shows both transient and persistent patterns. Event visualization may aid understanding of progression and support patient counseling.

Background: Alzheimer's dementia (AD) affects 6.9 million senior Americans and is a leading cause of death. Aspiration pneumonia carries high mortality but remains underexamined in this group. This study explores mortality patterns in this group to identify disparities among demographics.

Methods: We analyzed data from the CDC WONDER, focusing on mortality caused by the co-occurrence of AD and aspiration pneumonitis in adults aged 65 years and older from 1999 to 2020. Joinpoint Regression Program was employed to evaluate temporal trends. Age-adjusted mortality rates (AAMRs), crude mortality rates (CMRs) and annual percent changes (APCs) were computed.

Results: A total of 335,458 deaths occurred due to AD and aspiration pneumonia. The overall AAMR increased, with a significant increase from 1999 to 2001. Men had consistently higher AAMRs than women. AAMRs were highest among non-Hispanic (NH) Whites and lowest in NH Asians. CMR for the 85+ year age group was nearly four times higher than the 75-84 year age group.

Conclusion: Aspiration pneumonitis caused a large number of deaths in older adults with AD with some groups being more vulnerable. These results point to ongoing disparities and emphasize the importance of better preventive care and targeted interventions to reduce preventable deaths in these vulnerable groups.

Introduction: There are a few therapeutic approaches for Amyotrophic Lateral Sclerosis (ALS) which can only slow down or stop the disease progression for a limited period of time. Since it has been proven that Mesenchymal Stromal Cells (MSCs) produce neurotrophic factors and have some neuroprotective effects, stem cell therapy has been proposed as an alternative or add-on treatment for ALS patients.

Method & material: In this open-label clinical trial, two-repeated dose of 60 million GMP compliant Wharton's Jelly-derived Mesenchymal Stromal Cells (WJ-MSCs) were transplanted intrathecally (#6 patients) or intravenously (#6 patients) twice with a 3-month interval.

Results: No adverse events related to the intervention or injected cells were reported. While no significant improvement in the total revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) score or overall clinical efficacy was achieved, patients reported improvements in specific sub-items such as salivation, swallowing, and their speech. Additionally, reductions in muscle tremors and fasciculations, as well as increased muscle strength were observed.

Conclusion: In conclusion, using WJ-MSCs is safe and feasible in ALS patients, but the efficacy of these cells should be assessed in future studies with more patients, different routes of cell administration, and maybe with higher doses of the injected cells.

Aim: To understand medication adherence and associated healthcare costs of patients with early Alzheimer's disease (AD).

Methods: This retrospective cohort study used the Axon Registry® linked with claims data to examine medication adherence of U.S. patients with early AD (mild cognitive impairment [MCI] and mild dementia due to AD) from 2015 to 2022. Medication adherence was quantified by the proportion of days covered (PDC) over a one-year follow-up, and adherence rate was defined at a PDC ≥ 80%. Patient comorbidities and healthcare costs were described.

Results: Of 333 patients included, 213 (64%) were female with a median (IQR) age 79 (72-83) years. Patients had a mean (SD) of 2.3 (2.1) comorbidities and took a mean (SD) of 3.0 (1.5) medications. Weighted-average PDC across medications was 74.4% with 7 out of 10 medication classes having a medication adherence rate lower than 60%. DPP-4 inhibitors had the highest medication adherence rate (66.67% of patients), and memantine had the lowest (39.13% of patients). Annual median (IQR) medical and pharmacy costs per-patient were $5,268 ($1,808-$14,651) and $658 ($187-$2,736), respectively.

Conclusion: Patients with early AD had multiple comorbidities and took multiple medications. Suboptimal medication adherence and high healthcare costs were observed.

Background: While neuropsychiatric symptoms are common in Huntington's Disease (HD), there is a dearth of evidence about the effectiveness of psychotropic medication for treating behavioral and cognitive symptoms. This article systematically reviews and aggregates the evidence of the effects of antidepressants on individuals with early HD.

Methods: A systematic review and random-effects meta-analysis of RCTs comparing antidepressants to placebo in individuals with HD was performed, with a focus on outcomes of executive functioning, functional capacity, mood, motor function, and adverse events.

Results: A total of 4 studies with 123 of patients with early HD, of whom a total of 63 (51.2%) received an antidepressant, were identified in our search. In our pooled analysis, a modest but statistically significant improvement in mood resulted from antidepressant treatment in HD (OR -1.22; 95% CI -2.16,-0.27; p = 0.02). No significant differences in the other outcomes of interest were found following antidepressant exposure.

Conclusions: Our investigation suggests that antidepressant use may modestly improve mood, but not ameliorate functional, cognitive, or movement-related symptoms in mild HD. Further studies involving novel agents, larger samples, and longer follow-up times are needed to better characterize the effect of antidepressants on neuropsychiatric symptoms in HD.

Aims: Amyotrophic lateral sclerosis (ALS) is a motor neuron disease that progresses without periods of remission; few live more than five years beyond diagnosis. In this study we investigated the lived experiences of people diagnosed with ALS in the United States, in South Central Appalachia.

Patients & methods: We selected the philosophical and methodological approach of existential phenomenology of Merleau-Ponty to identify what was most important or figural to participants, within the contexts of Body, Other People, World, and Time.

Results: Through phenomenological interviews with 10 people living with ALS, six themes and 17 subthemes were identified covering the process of diagnosis, loss and devastation, support from others, assistive devices, a new purpose, and a change in perspective.

Conclusions: These themes offer insight into life with an ALS diagnosis so that this unique patient population may be better understood from a physical, medical, emotional, and spiritual standpoint.