The latest medical research on Neurodegenerative Disorders

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about neurodegenerative disorders gathered by our medical AI research bot.

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Prospective Five-Year Follow-Up of Patients with Schizophrenia Suspected with Parkinson's Disease.

Parkinsons Disease

It is difficult to distinguish patients with schizophrenia with neuroleptic-induced parkinsonism (NIP) from those with existing idiopathic Parkinson's disease when their striatal dopamine transporter uptake is reduced. There is a possibility of misdiagnosis of Parkinson's disease in patients with schizophrenia as schizophrenia with NIP, which leads to inappropriate treatment. This prospective study aimed at determining the underlying pathophysiology using detailed clinical and psychological assessments.

We enrolled six patients with schizophrenia who had parkinsonism and were diagnosed with Parkinson's disease according to the Movement Disorder Society Clinical Diagnostic Criteria, except for the fifth absolute exclusion criteria.

Five patients had been treated with neuroleptics for 20 years. One patient refused treatment for schizophrenia. All patients had impaired cognitive function at enrolment, olfactory dysfunction, and constipation. All patients were treated with dopaminergic therapy, and their parkinsonism substantially improved; one woman in her 40s experienced a wearing-off effect and dyskinesia. The uptake of dopamine transporter in the striatum decreased by 13%/year during the study period.

Some patients with schizophrenia and parkinsonism benefit from dopaminergic therapy. Some of these patients may also exhibit Lewy pathology.

Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia.

Molecular Neurodegeneration

Genetic mutations underlying familial Alzheimer's disease (AD) were identified decades ago, but the field is still in search of transformative therapies for patients. While mouse models based on overexpression of mutated transgenes have yielded key insights in mechanisms of disease, those models are subject to artifacts, including random genetic integration of the transgene, ectopic expression and non-physiological protein levels. The genetic engineering of novel mouse models using knock-in approaches addresses some of those limitations. With mounting evidence of the role played by microglia in AD, high-dimensional approaches to phenotype microglia in those models are critical to refine our understanding of the immune response in the brain.

We engineered a novel App knock-in mouse model (AppSAA) using homologous recombination to introduce three disease-causing coding mutations (Swedish, Arctic and Austrian) to the mouse App gene. Amyloid-β pathology, neurodegeneration, glial responses, brain metabolism and behavioral phenotypes were characterized in heterozygous and homozygous AppSAA mice at different ages in brain and/ or biofluids. Wild type littermate mice were used as experimental controls. We used in situ imaging technologies to define the whole-brain distribution of amyloid plaques and compare it to other AD mouse models and human brain pathology. To further explore the microglial response to AD relevant pathology, we isolated microglia with fibrillar Aβ content from the brain and performed transcriptomics and metabolomics analyses and in vivo brain imaging to measure energy metabolism and microglial response. Finally, we also characterized the mice in various behavioral assays.

Leveraging multi-omics approaches, we discovered profound alteration of diverse lipids and metabolites as well as an exacerbated disease-associated transcriptomic response in microglia with high intracellular Aβ content. The AppSAA knock-in mouse model recapitulates key pathological features of AD such as a progressive accumulation of parenchymal amyloid plaques and vascular amyloid deposits, altered astroglial and microglial responses and elevation of CSF markers of neurodegeneration. Those observations were associated with increased TSPO and FDG-PET brain signals and a hyperactivity phenotype as the animals aged.

Our findings demonstrate that fibrillar Aβ in microglia is associated with lipid dyshomeostasis consistent with lysosomal dysfunction and foam cell phenotypes as well as profound immuno-metabolic perturbations, opening new avenues to further investigate metabolic pathways at play in microglia responding to AD-relevant pathogenesis. The in-depth characterization of pathological hallmarks of AD in this novel and open-access mouse model should serve as a resource for the scientific community to investigate disease-relevant biology.

Impacts of Prism Adaptation Treatment on Spatial Neglect and Rehabilitation Outcome: Dosage Matters.

Neurorehabilitation and Neural Repair

We examined whether number of prism adaptation treatment (PAT) sessions in regular clinical practice would predict spatial neglect (SN) improvement...

Diagnosis and Clinical Features in Autoimmune-Mediated Movement Disorders.

Journal of Movement Disorders

Movement disorders are common manifestations in autoimmune-mediated encephalitis. This group of diseases is suspected to be triggered by infection ...

Development of Clinical Milestones in Parkinson's Disease After Bilateral Subthalamic Deep Brain Stimulation.

Journal of Movement Disorders

Deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson's disease (PD) patients does not halt disease progression, as these patients will progress and develop disabling non-levodopa responsive symptoms. These features may act as milestones that represent the overall functionality of patients after DBS. The objective of this study was to investigate the development of clinical milestones in advanced PD patients who underwent bilateral STN-DBS.

The study evaluated PD patients who underwent STN-DBS at baseline up to their last follow-up using the Unified Parkinson's Disease Rating Scale and Hoehn and Yahr scale. The symptoms of hallucinations, dysarthria, dysphagia, frequent falls, difficulty walking, cognitive impairment and the loss of autonomy were chosen as the clinical milestones.

A total of 106 patients with a mean age of 47.21 ± 10.52 years at disease onset, a mean age of 58.72 ± 8.74 years at surgery and a mean disease duration of 11.51 ± 4.4 years before surgery were included. Initial improvement of motor symptoms was seen after the surgery with the appearance of clinical milestones over time. Using the moderately disabling criteria, 81 patients (76.41%) developed at least one clinical milestone, while 48 patients (45.28%) developed a milestone when using the severely disabling criteria.

STN-DBS has a limited effect on axial and nonmotor symptoms of the PD patients, in contrast to the effect on motor symptoms. These symptoms may serve as clinical milestones that can convey the status of PD patients and its impact on the patients and their caregivers. Therefore, advanced PD patients, even those treated with bilateral STN-DBS, will still require assistance and cannot live independently in the long run.

Accuracy of Machine Learning Using the Montreal Cognitive Assessment for the Diagnosis of Cognitive Impairment in Parkinson's Disease.

Journal of Movement Disorders

The Montreal Cognitive Assessment (MoCA) is recommended for assessing general cognition in Parkinson's disease (PD). Several cutoffs of MoCA scores for diagnosing PD with cognitive impairment (PD-CI) have been proposed, with varying sensitivity and specificity. This study investigated the utility of machine learning algorithms using MoCA cognitive domain scores for improving diagnostic performance for PD-CI.

In total, 2,069 MoCA results were obtained from 397 patients with PD enrolled in the Parkinson's Progression Markers Initiative database with a diagnosis of cognitive status based on comprehensive neuropsychological assessments. Using the same number of MoCA results randomly sampled from patients with PD with normal cognition or PD-CI, discriminant validity was compared between machine learning (logistic regression, support vector machine, or random forest) with domain scores and a cutoff method.

Based on cognitive status classification using a dataset that permitted sampling of MoCA results from the same individual (n = 221 per group), no difference was observed in accuracy between the cutoff value method (0.74 ± 0.03) and machine learning (0.78 ± 0.03). Using a more stringent dataset that excluded MoCA results (n = 101 per group) from the same patients, the accuracy of the cutoff method (0.66 ± 0.05), but not that of machine learning (0.74 ± 0.07), was significantly reduced. Inclusion of cognitive complaints as an additional variable improved the accuracy of classification using the machine learning method (0.87-0.89).

Machine learning analysis using MoCA domain scores is a valid method for screening cognitive impairment in PD.

TREM2 in the pathogenesis of AD: a lipid metabolism regulator and potential metabolic therapeutic target.

Molecular Neurodegeneration

Triggering receptor expressed on myeloid cells 2 (TREM2) is a single-pass transmembrane immune receptor that is mainly expressed on microglia in th...

Effects of Vibration Training on Cognition and Quality of Life in Individuals With Multiple Sclerosis.

International J MS Care

Multiple sclerosis (MS) detrimentally affects cognition and quality of life (QOL). Interventions that can improve cognitive deficit and QOL in individuals with MS are desired. This pilot study investigated the possible effects of vibration training on improving cognition and QOL in individuals with MS.

Eighteen adults with MS were randomized into 2 groups: training and control. The training group underwent 6 weeks of vibration training, and the control group maintained their normal lifestyle throughout the study. In both groups, before and after the training course, the disability status was evaluated by the Patient Determined Disease Steps scale and the Multiple Sclerosis Functional Composite (MSFC), cognitive function was assessed by the Behavior Rating Inventory of Executive Function-Adults (BRIEF-A) and the Buschke Selective Reminding Test (SRT), and QOL was gauged by the 36-item Short Form Health Survey (SF-36).

The training was well accepted by the participants, and no major adverse event was reported. All participants finished the entire protocol. Compared with the control group, the training group showed greater improvements in MSFC score, Metacognition Index score of the BRIEF, SRT score, and physical domain score of the SF-36.

These results suggest that vibration training could be an effective alternative training paradigm to enhance cognition and QOL in individuals with MS, and they provide an encouraging base to conduct a large-scale clinical trial.

Sleep Quality in Neuromyelitis Optica Spectrum Disorder: A Systematic Review.

International J MS Care

This review summarizes the literature on sleep quality in neuromyelitis optica spectrum disorder (NMOSD) and discusses these findings in the context of current knowledge of sleep physiology.

A literature search was performed using Ovid MEDLINE, Embase, and Scopus from inception to September 3, 2020. All included studies reported at least 1 measure of sleep quality in individuals with NMOSD. Pittsburgh Sleep Quality Index (PSQI) scores of individuals from 4 studies were compared with those from a data set of controls.

Thirteen studies (1041 individuals with NMOSD) were included in the review. Disturbed sleep was demonstrated across subjective metrics based on patient surveys and objective metrics such as polysomnography. An estimated 70% of individuals with NMOSD can be classified as poor sleepers. Standardized mean difference between PSQI scores of 183 individuals with NMOSD and those of 9284 controls was 0.72 (95% CI, 0.57-0.86; P < .001). Decreased sleep quality was significantly associated with decreased quality of life and increased anxiety, depression, and disability status. Sleep disturbances in NMOSD were similar in severity to those in multiple sclerosis.

Sleep disturbances are a major contributor to NMOSD disease burden and may arise from the disruption of sleep circuitry, in addition to physical and psychological complications. Multiple processes involved in sleep regulation may be affected, such as, but not limited to, neural circadian circuit disruption, direct effects of inflammation, aminergic projecting system abnormalities, glymphatic system impairment, and development of sleep disorders such as restless legs syndrome/sleep apnea. A better understanding of these mechanisms is necessary for developing effective therapies for NMOSD-associated sleep disturbances.

Managing Cognitive Dysfunction in Multiple Sclerosis: A Snapshot of Changes in Screening, Assessment, and Treatment Practices.

International J MS Care

Cognitive dysfunction is prevalent in multiple sclerosis (MS) and can have a negative effect on several aspects of the daily lives of individuals with MS. In 2010, members of the Consortium of Multiple Sclerosis Centers (CMSC) were surveyed to understand MS clinicians' screening, assessment, and treatment practices for cognitive problems. Given the advancements made in the field in the past decade, it was deemed time to reevaluate how cognitive dysfunction is managed in the clinical setting.

An online questionnaire was completed by 56 CMSC members. They were asked to describe their clinical practices, procedures for screening and further evaluation, and treatment recommendations for cognitive dysfunction. Participants were also asked whether their practice had changed in terms of the number of cognitive screenings, prescriptions for cognitive problems, and referrals for neuropsychological assessment and cognitive remediation in the past 5 years to allow for clinicians who had not been in practice for 10 years.

Participants reported an increase in the number of cognitive screenings and referrals for neuropsychological assessments and cognitive remediation during the past 5 years. Compared with 2010, participants endorsed greater use of person-administered screening measures, such as the Symbol Digit Modalities Test, and fewer prescriptions for medications to improve cognitive functioning.

Clinical practices are becoming more in line with the literature, with increased use of cognitive screening and remediation. Continued attention to cognitive problems will be an ongoing important component of MS-related care.

Motivation for Physical Activity in Adults With Multiple Sclerosis: A Self-determination Theory-Based Approach.

International J MS Care

Despite the benefits of regular physical activity (PA), most adults with multiple sclerosis (MS) are insufficiently active. Identifying the motivational correlates of PA is necessary to facilitate health behavior change. The extent to which the constructs of psychological need satisfaction and motivational regulations associate with self-determined PA in adults with the disease was examined.

Individuals with MS were provided a link to a web-based survey. There were 290 respondents: 242 women and 48 men aged 22 to 71 (mean ± SD, 49.50 ± 12.05) years with primarily mild to moderate mobility impairment who completed the Psychological Need Satisfaction in Exercise scale, the Behavioral Regulation in Exercise Questionnaire, and the International Physical Activity Questionnaire.

Path analysis revealed that PA was best predicted by integrated regulation, competence, and mobility, explaining 28% of the variance in PA behavior. All 3 need satisfaction variables (relatedness, competence, and autonomy) and mobility impairment accounted for 43% of the variance in integrated regulation.

Increasing satisfaction of the need for relatedness, competence, and autonomy can lead to more integrated and internally motivated PA engagement in adults with MS.

The Impact of COVID-19 on the Lives of Individuals With Multiple Sclerosis: 1 Year Into the Pandemic.

International J MS Care

The COVID-19 pandemic resulted in implementation of restrictive public health policies requiring people to limit or avoid interaction with others. These policies also had an economic impact. Individuals with multiple sclerosis (MS) already experience higher incidences of depression, anxiety, social isolation, and job loss, and the continuing pandemic may exacerbate these.

Between November 2, 2020, and February 12, 2021, 233 individuals with MS completed the Hospital Anxiety and Depression Scale, the modified Medical Outcomes Study Social Support Survey, the Centers for Disease Control/National Institutes of Health Common Data Element Repository economic impact questions, and study team-designed questions about social and family relationships and adherence to public health policies.

Study participants reported high rates of mask wearing, good hand hygiene, and limited interactions with those outside their homes. They felt isolated from family they did not live with, friends, and coworkers. The frequency of conflicts with their spouses/partners increased "a little" among 20% of respondents, but overall relationships with housemates were "unchanged" or "a little better." Ninety-one percent of participants reported experiencing no financial impact. On the Hospital Anxiety and Depression Scale, 16.0% of 218 respondents reported depressive symptoms and 26.8% of 216 reported symptoms of anxiety above the commonly accepted clinically significant cutoff points. Only 3.4% of participants reported contracting SARS-CoV-2.

During the first year of the pandemic, this study found no pronounced impact on the emotional, social, or economic stability of the individuals with MS it surveyed. It seems that these study participants adapted to the restrictions created by the pandemic and, by adhering to guidelines, protected themselves from contracting SARS-CoV-2.