Neurodegenerative Diseases最新文献

Introduction: Experimental data suggest sexual dimorphism in the Locus Coeruleus (LC), with females exhibiting higher neuronal count and noradrenergic activity. In Alzheimer's Disease (AD), progressive LC dysfunction may contribute early to pathogenesis, and female sex is a key risk factor for AD. This study aimed to investigate if such sex differences exist in humans and whether they influence the relationship between LC degeneration and AD features, such as cortical atrophy and cognitive decline.

Methods: Fifty-three healthy controls (HC), 70 Mild Cognitive Impaired (MCI) subjects, and 29 Alzheimer's Disease Demented (ADD) patients underwent high-field brain MRI with LC-sensitive sequences following detailed neuropsychological and neurological assessments. LC integrity was measured using the LC Contrast Ratio (LCCR) parameter based on a previously published template approach.

Results: Within the HC and MCI groups, females showed higher LCCR values than males. A significant sex effect was observed in the relationship between LC integrity and cortical volume in the frontotemporal cortices, with males showing a stronger association.

Conclusion: LC structure and function may differ between sexes, influencing AD pathophysiology through distinct mechanisms. While this sexual dimorphism may have a minor role, it should be considered in clinical investigations and drug development research.

Introduction: Huntington's disease (HD) is considered a rare and fatal neurodegenerative disease; despite that, only one study described the outcomes among those with HD and COVID-19. In this context, an epidemiological investigation was conducted in Brazil using the data from OpenDataSUS (https://opendatasus.saude.gov.br/), a Brazilian open dataset encompassing demographic and clinical information of hospitalized patients.

Method: The study comprised 2,180,403 hospitalized patients due to COVID-19 in Brazil from December 29th, 2019, to April 6th, 2023. From the totality of the original data, patients with HD and three control populations [Control 1 (CG-1) - hospitalized patients with COVID-19 and a neurological disorder (except those with HD), Control 2 (CG-2) - hospitalized patients with COVID-19 and without comorbidities, and Control 3 (CG-3) - hospitalized patients with COVID-19 except for those with HD] were selected. The study described the following characteristics of these patients: sex, age, race, place of residence, presence of nosocomial infection, clinical signs, comorbidities, use of antiviral for Flu, need for intensive care unit, need for mechanical ventilation support, discharge criteria, and outcome.

Results: A total of 60 patients with HD were enrolled representing a prevalence of 2.8 per 100,000 inhabitants. Of these, 23 were men, 30 were aged between 25 and 60 years, 38 were White people, 58 lived in an urban area, and two presented with nosocomial infection. The main clinical signs presented were fever (45), dyspnea (45), peripheral oxygen saturation <95% (45), cough (38), and respiratory discomfort (37). The main comorbidities were cardiomyopathy (13), asthma (2), and chronic lung disease (2). Four patients received the antiviral for the Flu. During the hospitalization, 18 patients required admission to an intensive care unit, 10 used invasive mechanical ventilation, 42 used non-invasive mechanical ventilation, and eight did not use ventilatory support. Regarding outcomes, 36 patients were cured, 23 died due to COVID-19, and one died, and the cause of death was not associated with the COVID-19. In the comparison of markers between patients with HD and the controls, the following significant associations were described: (CG-1) patients with HD were younger, and presented fewer clinical signs and comorbidities; (CG-2) patients with HD were commonly female, were older, presented fewer clinical signs and a higher chance of death [OR = 2.354 (95%CI = 1.395 to 3.973)]; and (CG-3) patients with HD were commonly female, and presented fewer clinical signs and comorbidities.

Conclusions: Patients with HD can only be considered an at-risk population due to the poor clinical outcomes when compared to patients without comorbidities. Even then, this group of patients presented fewer clinical signs and comorbidities.

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are chronic neuroinflammatory conditions that disproportionately affect women, with a 2:1 ratio in MS and up to 8.9:1 in NMOSD. Cognitive impairment is one of the earliest and most debilitating symptoms of MS, while mood disorders are common and significantly impact the quality of life and disease prognosis. Understanding sex differences in disease progression, particularly the potential differences in the mechanisms behind disability, is critical for advancing patient care. This review synthesizes current knowledge of sex-specific differences in MS and NMOSD, with a focus on neuroinflammation and neurodegeneration, as well as cognitive symptoms, and psychiatric comorbidities. The current state of research highlights the role of hormonal changes over the patient lifespan, such as estrogen and testosterone, as well as their role in modulating neuroinflammatory responses and subsequent neurodegeneration. Lastly, we discuss implications for disease monitoring and furthering knowledge in the field with a sex-specific lens, including recommendations for evaluating sex differences and personalized care in MS and NMOSD.

Introduction: Multiple studies report sex and gender differences in Lewy body dementia (LBD); however, there is a paucity of research investigating social determinants associated with LBD.

Methods: Participants with LBD (51 females, 79 males) and controls with similar age (64 females, 60 males) completed remote surveys assessing various social and demographic variables, and age at LBD onset for LBD group. Sex-stratified comparisons for LBD and control groups; comparisons of females and males with LBD were done for social determinants. Sex differences for onset age were further analyzed with linear models adjusting for significantly differing social variables between the sexes.

Results: LBD group had lower years of education, income, subjective social status than controls; with larger differences for males than females (p<.05 for all). Higher percentage of females with LBD were living alone (p=.016) and not married/partnered (p=.002) compared to males with LBD. Adjusting for social variables that differed between the sexes, females were younger at cognitive impairment onset (p=.037) and diagnosis (p=.032). For the overall cohort, being ethnoracially minoritized, sexual and gender minoritized, and having lower education quality were associated with younger age at symptom onset (p<.049 for all). For females, lower childhood subjective social status (p=.037); for males, being ethnoracially minoritized (p<.001) and lower years of education (p=.031) were associated with younger age at diagnosis.

Conclusion: Social determinants, even during childhood can impact the LBD onset differently for females and males. Interactions between biological and social factors need to be investigated further with inclusive and diverse cohorts in LBD.

Introduction: Recently, studies have suggested a role of motor symptom asymmetry on impaired emotional recognition abilities in Parkinson's disease with a greater vulnerability in patients with a predominance of left-sided symptoms. However, none of them explored the interaction between motor symptom asymmetry and dopamine replacement therapy in different stages of the disease.

Methodology: We explored the recognition of vocal emotion (i.e., emotional prosody) in 15 newly diagnosed Parkinson's disease patients in the early stages of the disease, 15 patients in the advanced stages of the disease and 15 healthy controls. The early patients were studied in two conditions: ON and OFF dopaminergic replacement therapy and both Parkinson's disease groups (early and advanced) were divided into two subgroups according to the asymmetry of motor symptoms.

Results: The analyses revealed two patterns of results. First, as predicted, we observed a reduction in performance for the recognition of vocal emotions in patients with a predominance of left-sided symptoms as compared to both healthy controls and predominantly right-sided symptom patients. Second, in the early stages of the disease, we observed a deleterious effect of dopatherapy on the recognition of vocal emotions for the patients with left-predominant symptoms, and the inverse pattern (i.e., a positive effect of dopatherapy) for the patients with right-predominant symptoms.

Conclusions: Our results bring to knowledge the differential effects of disease duration, dopaminergic replacement therapy and motor symptom asymmetry on vocal emotion recognition in Parkinson's disease.

Introduction: Essential tremor (ET) is a highly prevalent neurological disease. At present, there are no clinical biomarkers. Neurofilament light (NfL) has been studied as a measure of neuronal damage in a considerable number of neurological disorders. There have been three studies of ET, and results are inconsistent.

Methods: Forty ET cases were enrolled in a research study between February and November 2023 and compared to two control groups from study 1 (n = 41) and study 2 (n = 185). Total tremor score was a measure of the severity of action tremor. Blood samples were analyzed for serum NfL level on the Simoa® platform using an NF-Light™ kit as a marker of axonal injury.

Results: Serum log NfL levels were higher in ET cases than controls in study 1 (p < 0.001) and study 2 (p < 0.001). In a multivariate linear regression model, ET cases (p = 0.03) and individuals of older age (p < 0.001) had higher serum log NfL levels than controls (combined in studies 1 and 2). There was no association in ET cases between serum log NfL level and total tremor score (Pearson's r = 0.08, p = 0.63).

Conclusion: This new study further validates the elevation in serum NfL levels in ET, now representing the third study to do so. In combination, the converging data suggest that there is an overall increase in serum NfL levels in ET. The demonstration of elevated serum levels of NfL in ET adds an additional piece of evidence that there is neuronal damage in ET.

Background: Over the past few decades, advances in the neurology of aging have been considerable and have led to a better understanding of the science of age-related neurological disorders. Likewise, it changed the perception of classical neurology practice, research, and the way of looking at age-related conditions. Neurological disorders are the most frequent cause of major disability in the elderly and account for almost half of the incapacitation occurring beyond age 65 and more than 90% of serious dependency. However, a number of neurological changes occur also in the absence of a specific disease, making the assessment and management of neurological complaints and findings a specific expertise.

Summary: Maximizing success in clinical care of the elderly requires expertise in geriatric neurology, which includes an understanding of current research regarding aging and age-related neurological dysfunctions, and the ability to work with other geriatric healthcare providers. Although current therapies for neurodegenerative diseases mainly offer symptomatic relief without slowing progression, the landscape is evolving. Biomarkers of pathology and neuroimaging have continued to develop, with a significant impact on diagnosis and treatment. These advances have not only helped to improve our knowledge of disease pathophysiology but also disease stages, guiding symptomatic monitoring, and possible therapeutic options at a pre-symptomatic stage.

Key messages: Neurological disorders are a leading cause of major disability and dependency in the elderly, underscoring the need for expertise in geriatric neurology for effective clinical care of this population. Although current therapies for neurodegenerative diseases primarily provide symptomatic relief without slowing disease progression, advancements in biomarkers and neuroimaging are significantly evolving. These advancements enhance our understanding of disease pathophysiology and stages, guiding symptomatic monitoring and potential therapeutic options at a pre-symptomatic stage. As knowledge about age-associated conditions is steadily rising and geriatric medicine gains further recognition, this article argues for a new focus on the role of neurologists in geriatric medicine, emphasizing the importance of integrating current research and collaborative care approaches in the management of elderly patients.

Introduction: Motoric cognitive risk (MCR) and amnestic mild cognitive impairment (aMCI) syndromes are each reliable predictors of incident Alzheimer's disease (AD), but MCR may be a stronger predictor of vascular dementia than AD. This study contrasted cortical and hippocampal atrophy patterns in MCR and aMCI.

Methods: Cross-sectional data from 733 older adults without dementia or disability (M age = 73.6; 45% women) in the multicountry MCR consortium were examined. MCR was defined as presence of slow gait and cognitive concerns. Amnestic MCI was defined as poor episodic memory performance and cognitive concerns. Cortical thickness and hippocampal volumes were quantified from structural MRIs. Multivariate and univariate general linear models were used to examine associations between cortical thickness and hippocampal volume in MCR and aMCI, adjusting for age, sex, education, total intracranial volume, white matter lesions, and study site.

Results: The prevalence of MCR and aMCI was 7.64% and 12.96%, respectively. MCR was associated with widespread cortical atrophy, including prefrontal, insular, cingulate, motor, parietal, and temporal atrophy. aMCI was associated with hippocampal atrophy.

Conclusion: Distinct patterns of atrophy were associated with MCR and aMCI. A distributed pattern of cortical atrophy - that is more consistent with VaD or mixed dementia- was observed in MCR. A more restricted pattern of atrophy - that is more consistent with AD - was observed in aMCI. The biological underpinnings of MCR and aMCI likely differ and may require tailored interventions.

Introduction: Parkinson's disease (PD) reduces an individual's capacity for automaticity which limits their ability to perform two tasks simultaneously, negatively impacting daily function. Understanding the neural correlates of dual tasks (DTs) may pave the way for targeted therapies. To better understand automaticity in PD, we aimed to explore whether individuals with differing DT performances possessed differences in brain morphologic characteristics.

Methods: Data were obtained from 34 individuals with PD and 47 healthy older adults including (1) demographics (age, sex), (2) disease severity (Movement Disorder Society - Unified Parkinson's Disease Rating Scale [MDS-UPDRS], Hoehn and Yahr, levodopa equivalent daily dose [LEDD]), (3) cognition (Montreal Cognitive Assessment), (4) LEDD, (5) single-task and DT performance during a DT-timed-up-and-go test utilizing a serial subtraction task, and (6) cortical thicknesses and subcortical volumes obtained from volumetric MRI. Participants were categorized as low or high DT performers if their combined DT effect was greater than the previously determined mean value for healthy older adults (μ = -74.2). Nonparametric testing using Quade's ANCOVA was conducted to compare cortical thicknesses and brain volumes between the highDT and lowDT groups while controlling for covariates: age, sex, MDS-UPDRS part III, LEDD, and intracranial volume. Secondarily, similar comparisons were made between the healthy older adult group and the highDT and lowDT groups. Lastly, a hierarchical linear regression model was conducted regressing combined DT effect on covariates (block one) and cortical thicknesses (block 2) in stepwise fashion.

Results: The highDT group had thicker cortices than the lowDT group in the right primary somatosensory cortex (p = 0.001), bilateral primary motor cortices (p ≤ 0.001, left; p = 0.002, right), bilateral supplementary motor areas (p = 0.001, left; p < 0.001, right), and mean of the bilateral hemispheres (p = 0.001, left; p < 0.001, right). Of note, left primary cortex thickness (p = 0.002), left prefrontal cortex thickness (p < 0.001), and right supplementary motor area thickness (p = 0.003) differed when adding a healthy comparison group. Additionally, the regression analysis found that the left paracentral lobule thickness explained 20.8% of the variability in combined DT effect (p = 0.011) beyond the influence of covariates.

Conclusions: These results suggest regions underlying DT performance, specifically, a convergence of neural control relying on sensorimotor integration, motor planning, and motor activation to achieve higher levels of DT performance for individuals with PD.