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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Metabolomics-Based Effects of a Natural Product on Remyelination After Cerebral Ischemia Injury Via GABABR-pCREB-BDNF Pathway.

Neurorehabilitation and Neural Repair

Yi-Qi-Tong-Luo Granules (YQTLs) is a natural compound of Traditional Chinese Medicine authorized by China Food and Drug Administration (CFDA). These granules are employed in the convalescent stage of cerebral infarction and render notable clinical efficacy. This study aims to uncover the underlying mechanisms of YQTLs on remyelination after cerebral ischemia injury.

We established cerebral ischemia model in rats using microsphere-induced multiple cerebral infarction (MCI). We evaluated the pharmacological effects of YQTLs on MCI rats, through Morri's water maze test, open field test, hematoxylin and eosin staining, and glycine silver immersion. We employed liquid chromatography mass spectrometry metabolomics to identify differential metabolites. Enzyme-linked immunosorbent assay was utilized to measure the release of neurotrophins, while immunofluorescence staining was used to assess oligodendrocyte precursor cells differences and myelin regeneration. We used Western blotting to validate the protein expression of remyelination-associated signaling pathways.

YQTLs significantly improves cognitive function following cerebral ischemia injury. Pathological tissue staining revealed that YQTLs administration inhibits neuronal denaturation and neurofibrillary tangles. We identified 141 differential metabolites among the sham, MCI, and YQTLs-treated MCI groups. Among these metabolites, neurotransmitters were identified, and notably, gamma-aminobutyric acid (GABA) showed marked improvement in the YQTLs group. The induction of neurotrophins, such as brain-derived neurotrophic factor (BDNF) and PDGFAA, upregulation of olig2 and MBP expression, and promotion of remyelination were evident in YQTLs-treated MCI groups. Gamma-aminobutyric acid B receptors (GABABR), pERK/extracellular regulated MAP kinase, pAKT/protein kinase B, and pCREB/cAMP response element-binding were upregulated following YQTLs treatment.

YQTLs enhance the binding of GABA to GABABR, thereby activating the pCREB/BDNF signaling pathway, which in turn increases the expression of downstream myelin-associated proteins and promotes remyelination and cognitive function.

Characterizing Heart Rate Variability Response to Maximal Exercise Testing in People with Huntington's Disease.

Journal of Huntingtons Disease

Huntington's disease (HD) is an autosomal dominant, neurodegenerative disease that involves dysfunction in the autonomic nervous system (ANS). Heart rate variability (HRV) is a valid and noninvasive measure for ANS dysfunction, yet no study has characterized HRV response to exercise in people with HD.

Characterize HRV response to exercise in individuals with HD and explore its implications for exercise prescription and cardiac dysautonomia mechanisms.

19 participants with HD were recruited as part of a cohort of individuals enrolled in the Physical Activity and Exercise Outcomes in Huntington's Disease (PACE-HD) study at Teachers College, Columbia University (TC). 13 non-HD age- and gender-matched control participants were also recruited from TC. HRV was recorded with a Polar H10 heart rate (HR) monitor before, during, and after a ramp cycle-ergometer exercise test.

Participants with HD showed reduced HR peak (p < 0.01) and HR reserve (p < 0.001) compared with controls. Participants with HD demonstrated reduced root mean square of successive differences between normal-to-normal intervals (RMSSD) and successive differences of normal-to-normal intervals (SDSD) at rest (p < 0.001). Participants with HD also showed differences for low frequency (LF) power (p < 0.01), high frequency (HF) normalized units (nu) (p < 0.05), LF (nu) (p < 0.001), and HF/LF ratio (p < 0.05) compared with controls.

We found reduced aerobic exercise capacity and sympathovagal dysautonomia both at rest and during post-exercise recovery in people with HD, suggesting modified exercise prescription may be required for people with HD. Further investigations focusing on cardiac dysautonomia and underlying mechanisms of sympathovagal dysautonomia in people with HD are warranted.

Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats.

Journal of Huntingtons Disease

Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric dysfunction caused by a mutant huntingtin protein. Compromised metabolic activity resulting from systemic administration of the mitochondrial toxin, 3-nitropropionic acid (3-NP), is known to mimic the pathology of HD and induce HD-like symptoms in rats. N-hexanoic-Tyr-Ile-(6)-amino hexanoic amide (PNB-0408), also known as Dihexa, has been shown to have neuroprotective and procognitive properties in animal models of Alzheimer's and Parkinson's diseases. Given the mechanism of action and success in other neurodegenerative diseases, we felt it an appropriate compound to investigate further for HD.

The present study was designed to test if PNB-0408, an angiotensin IV analog, could attenuate 3-NP-induced HD-like symptoms in rats and serve as a potential therapeutic agent.

Forty male Wistar rats were randomized into three groups consisting of a "vehicle" group, a "3-NP" group, and a "3-NP + PNB-0408" group. PNB-0408 was administered along with chronic exposure to 3-NP. Animal body weight, motor function, and cognitive abilities were measured for five weeks, before euthanasia and histopathological analysis.

Exposure to 3-NP decreased the amount of weight rats gained, impaired spatial learning and memory consolidation, and led to marked motor dysfunction. From our observations and analysis, PNB-0408 did not protect rats from the deficits induced by 3-NP neurotoxicity.

Our findings suggest that PNB-0408 may not be an efficacious treatment strategy for preventing 3-NP-induced HD-like symptoms in a preclinical model. These data highlight the need for further research of this compound in alternate models and/or alternative approaches to managing this disorder.

Freesurfer Software Update Significantly Impacts Striatal Volumes in the Huntington's Disease Young Adult Study and Will Influence HD-ISS Staging.

Journal of Huntingtons Disease

The Huntington's Disease Integrated Staging System (HD-ISS) defined disease onset using volumetric cut-offs for caudate and putamen derived from Freesurfer 6 (FS6). The impact of the latest software update (FS7) on volumes remains unknown. The Huntington's Disease Young Adult Study (HD-YAS) is appropriately positioned to explore differences in FS bias when detecting early atrophy.

Explore the Relationships and differences between raw caudate and putamen volumes, calculated total intracranial volumes (cTICV), and adjusted caudate and putamen volumes, from FS6 and FS7, in derived from HD-YAS.

Images from 123 participants were segmented and quality controlled. Relationships and differences between volumes were explored using intraclass correlation (ICC) and Bland-Altman analysis.

Across the whole cohort, ICC for raw caudate and putamen was 0.99, cTICV 0.93, adjusted caudate 0.87, and adjusted putamen 0.86 (all p <  0.00005). Compared to FS6, FS7 calculated: i) larger raw caudate (+0.8%, p <  0.00005) and putamen (+1.9%, p <  0.00005), with greater difference for larger volumes; and ii) smaller cTICV (-5.1%, p <  0.00005), with greater difference for smaller volumes. The systematic and proportional difference in cTICV was greater than raw volumes. When raw volumes were adjusted for cTICV, these effects compounded (adjusted caudate +7.0%, p <  0.00005; adjusted putamen +8.2%, p <  0.00005), with greater difference for larger volumes.

As new software is released, it is critical that biases are explored since differences have the potential to significantly alter the findings of HD trials. Until conversion factors are defined, the HD-ISS must be applied using FS6. This should be incorporated into the HD-ISS online calculator.

Huntington's Disease Clinical Trials Update: February 2024.

Journal of Huntingtons Disease

In this edition of the Huntington's Disease Clinical Trials Update, we expand on the ongoing program from VICO Therapeutics and on the recently ter...

Recognition, Description, and Variability of Spasticity in Individuals With Multiple Sclerosis and Potential Barriers to Clinician-Patient Dialogue: Results From SEEN-MSS, a Large-Scale, Self-Reported Survey.

International J of MS Care

The experience with spasticity varies among individuals with multiple sclerosis and spasticity (MSS), as they may not recognize it as spasticity or have the language to describe their symptoms. This can lead to potential delays in diagnosis and treatment.

Symptoms and Emotions Exploration Needed in Multiple Sclerosis Spasticity was an online survey completed by 1177 individuals with MSS in 2021. It sought to capture symptoms of spasticity, variability of symptoms, specific spasticity triggers, and how conversations with physicians were initiated.

The mean age of the cohort was 56.8 years and it was 78% women. Prior to spasticity onset, 65% of respondents felt minimally prepared or unprepared for possibly developing spasticity and were unaware that spasticity manifests as part of MS. Eighty percent experienced spasticity daily, which was variable in severity and duration. Spasticity was triggered by a range of factors and 90% of those surveyed were unable to predict when it would occur or its severity. Day-to-day variability of spasticity prevented 65% of respondents from doing things they wished to do. Sixty percent were confused by their symptoms, not recognizing them as spasticity. Although 91% reported experiencing muscle spasms, only 69% used "muscle spasms" to describe their symptoms. Other descriptors included "muscle tightness," "stiffness," "cramping," and "pain." After recognizing spasticity, 78% proactively initiated discussions with their physicians, 52% wished they had done so sooner, and 42% delayed the conversation by up to or more than a year.

Results emphasize the variable nature of spasticity and the lack of a common language to describe symptoms, underscoring the importance of education, earlier recognition, and customized treatments tailored to the severity and duration of spasticity symptoms.

Effect of Foot Reflexology on Patients With Multiple Sclerosis: A Systematic Review of Current Evidence.

International J of MS Care

Individuals with multiple sclerosis (MS) commonly experience fatigue, discomfort, sleep problems, anxiety, and reduced quality of life. Studies have shown that foot reflexology can help relieve these symptoms. The objective of this current study is to systematically review the effects of foot reflexology on patients with MS.

We conducted a systematic review of published literature in many databases, including PubMed, EMBASE, and Cochrane Library, from January 1, 2000, to January 27, 2022. With language restrictions, we included randomized controlled trials of foot reflexology interventions for MS that had any clinical or psychological symptom measurements as outcomes. The Cochrane risk-of-bias tool was used to assess evidence quality. Two authors independently screened titles and abstracts. Potential eligible articles were retrieved for full-text review. A third author checked for excluded records. All discrepancies were resolved through a discussion among the 4 reviewing authors.

A total of 154 studies were identified; 9 studies with 545 MS patients were included in this review. The most frequently reported findings of foot reflexology intervention in individuals with MS were reductions in fatigue, pain, muscle spasms, stiffness, and psychological symptoms and improvement in bowel and bladder functions and quality of life.

The findings suggest that foot reflexology could be a safe and effective modality to reduce the physical and psychological symptoms and also improve the quality of life for individuals with MS; however, well-designed, large-scale trials are required to confirm the effect.

Association Between Improved Serum Fatty Acid Profiles and Cognitive Function During a Dietary Intervention Trial in Relapsing-Remitting Multiple Sclerosis.

International J of MS Care

Cognitive impairment is a common multiple sclerosis (MS)-related symptom that impacts quality of life (QOL). Diet interventions are shown to be beneficial in managing QOL, and the intake of essential fatty acids is linked with improved cognitive function. However, the effect of diets on serum fatty acid profiles and cognitive function is unknown.

A previous randomized, parallel-arm trial recruited participants with relapsing-remitting MS (N = 77). Study visits included 4 time points: run-in, baseline, 12 weeks, and 24 weeks. During the run-in phase, participants followed their usual diet and were then randomly assigned to either a modified paleolithic (Wahls) or a low saturated fat (Swank) diet at baseline. Assessments at study visits included cognitive function assessed by Symbol Digit Modalities Test-Oral (SDMT-O) and Perceived Deficits Questionnaire (PDQ), and serum fatty acids, including eicosapentaenoic (EPA), docosahexaenoic (DHA), and arachidonic (ARA) acids.

Both groups had significant improvements in all serum fatty acids (P < .01), except for ARA, as well as SDMT-O at 24-weeks (P < .05), total PDQ at 12 and 24 weeks (P < .01) compared with baseline values. The 12-week changes in ω-3 (EPA + DHA) index and EPA serum fatty acids were associated with SDMT-O changes (P ≤ .05); however, the changes in fatty acid levels did not mediate the effect of the diets on SDMT-O or PDQ (P > .05).

Both diets led to improvements in serum fatty acid profiles and cognitive function, with associations between the 12-week ω-3 (EPA + DHA) index and EPA changes with SDMT-O.

Investigating the Impact of Polypharmacy and Anticholinergic Medication Burden on Objective Cognitive Performance in Adults With Multiple Sclerosis.

International J of MS Care

Polypharmacy, or the use of 5 or more daily medications, is common in adults with multiple sclerosis (MS), and is often due to various physical, cognitive, and emotional symptoms. However, research regarding the association between polypharmacy and cognitive outcomes in MS is sparse. Furthermore, individuals with MS often use medications with anticholinergic properties, which are commonly associated with cognitive impairment and other central nervous system adverse effects. Currently, the utility of scales measuring anticholinergic burden in MS is unknown. This study aims to investigate the relationship between polypharmacy, anticholinergic burden, and objective cognitive performance in MS.

We recruited 90 individuals with MS during routine visits at an MS specialty clinic in Kansas City. Participants completed a brief, virtual cognitive assessment and answered questions about their health. Participants provided their medication lists from which we determined polypharmacy and scores on several anticholinergic burden scales. Statistical analyses included Spearman correlations and linear regression models.

Approximately 44% of the individuals surveyed met the criteria for polypharmacy. The number of daily medications was negatively correlated with cognitive performance (rs = -0.45, P < .001). Further, the Drug Burden Index accounted for additional variance in cognitive performance beyond that explained by age, education, MS disease duration, and comorbidities [ΔR2 = .12, F(5, 84) = 7.84, P < .001.].

Clinicians should consider the possible negative consequences of polypharmacy when addressing cognitive concerns in MS. Anticholinergic burden scales may be valuable in this regard. Future investigations could explore behavioral and pharmacological interventions aimed at reducing polypharmacy in MS.

Validated, Quantitative, Machine Learning-Generated Neurologic Assessment of Multiple Sclerosis Using a Mobile Application.

International J of MS Care

The BeCare MS Link mobile app collects data as users complete different in-app assessments. It was specifically developed to evaluate the symptomatology and neurologic function of patients with multiple sclerosis (MS) and to become a digital equivalent of the Expanded Disability Status Scale (EDSS) and other standard clinical metrics of MS progression.

Our research compared EDSS scores derived from the BeCare MS link app to EDSS scores derived from neurologist assessment for the same cohort of 35 patients diagnosed with MS. App-derived data were supplied to 4 different machine learning algorithms (MLAs) with an independent EDSS score prediction generated from each. These scores were compared with the clinically derived EDSS score to assess the similarity of the scores and to determine an accuracy estimate for each.

Of the 4 MLAs employed, the most accurate MLA produced 19 EDSS score predictions that exactly matched the clinically derived scores, 21 score predictions within 0.5 EDSS points, and 32 score predictions within 1 EDSS point. The remaining MLAs also provided a relatively high level of accuracy in predicting EDSS scores when compared with clinically derived EDSS, with over 80% of scores predicted within 1 point and a mean squared error with a range of 1.05 to 1.37.

The BeCare MS Link app can replicate the clinically derived EDSS assessment of a patient with MS. The app may also offer a more complete evaluation of disability in patients with MS.

Physical Activity in Individuals Newly Diagnosed With Multiple Sclerosis Through the Lens of the COM-B Model.

International J of MS Care

Physical activity (PA) is a promising intervention for disease modification and symptom management in multiple sclerosis (MS); however, there is a lack of research focusing on PA behavior change interventions for persons newly diagnosed with MS. Such PA behavior change interventions should be developed based on a strong empirical foundation of understanding the behavior and its determinants (ie, what to target for changes to occur). To that end, this qualitative study examined factors explaining PA in persons newly diagnosed with MS and identified potential targets for future behavior change intervention development based on the Capability-Opportunity-Motivation-Behavior (COM-B) model.

Twenty individuals diagnosed with MS within the past 2 years underwent one-on-one semistructured interviews using questions developed based on the COM-B model. Data were analyzed using reflective thematic analysis, and the identified themes were then mapped with the COM-B model.

Factors explaining PA in the study sample were identified across the COM-B components. The typical factors include knowledge and skills to sufficiently engage in PA with appropriate approaches, ability to adapt and navigate through new environmental and social difficulties after diagnosis, and motivation resulting from a combination of factors, such as outcome expectation, belief of capabilities, role/identity, reinforcement, and emotions.

The COM-B model was applied successfully in this study to understand PA behavior and identify potential targets for behavior change in individuals newly diagnosed with MS. Future behavior change interventions should consider addressing these factors to generate effective PA behavior change in this population.

Multiple Sclerosis, Fatigue, Expanded Disability Status Scale: A Cross-Sectional Exploration of Sleep Efficiency and Quantitative Sleep Parameters.

International J of MS Care

Poor sleep quality and sleep disorders are more prevalent in individuals with multiple sclerosis (MS) than in the general population. Poor sleep has been correlated with worse MS outcomes. Sleep efficiency (SE) is one of the most sensitive markers of sleep quality. There is very little written about SE and other polysomnography (PSG) parameters and MS measures.

This is a retrospective review of 280 consecutive individuals with MS evaluated by PSGs and other standardized MS measures over 13 years at a comprehensive MS center. In addition, the cohort was assessed with 2 fatigue scales, the Epworth Sleepiness Scale, and the Expanded Disability Status Scale. A comparison of means test (independent t test) and a correlation coefficient (r) were used.

The PSG measures of SE and Total Sleep Time were significantly different between a group of individuals with MS with a disease duration of more than 5 years vs a group of individuals with MS with a disease duration less than or equal to 5 years. Prevalence of obstructive sleep apnea was 63%, higher than reported in the literature while the prevalence of moderate to severe obstructive sleep apnea was 33.4%, which was lower than reported.

Longer disease duration and worse disability correlate with sleep quality as measured by SE.