Memory Loss Research Articles

Quantitative evaluation of Scout Accelerated Motion Estimation and Reduction (SAMER) MPRAGE for morphometric analysis of brain tissue in patients undergoing evaluation for memory loss

BackgroundThree-dimensional (3D) T1-weighted MRI sequences such as the magnetization prepared rapid gradient echo (MPRAGE) sequence are important for assessing regional cortical atrophy in the clinical evaluation of dementia but have long acquisition times and are prone to motion artifact. The recently developed Scout Accelerated Motion Estimation and Reduction (SAMER) retrospective motion correction method addresses motion artifact within clinically-acceptable computation times and has been validated through qualitative evaluation in inpatient and emergency settings. MethodsWe evaluated the quantitative accuracy of morphometric analysis of SAMER motion-corrected compared to non-motion-corrected MPRAGE images by estimating cortical volume and thickness across neuroanatomical regions in two subject groups: (1) healthy volunteers and (2) patients undergoing evaluation for dementia. In part (1), we used a set of 108 MPRAGE reconstructed images derived from 12 healthy volunteers to systematically assess the effectiveness of SAMER in correcting varying degrees of motion corruption, ranging from mild to severe. In part (2), 29 patients who were scheduled for brain MRI with memory loss protocol and had motion corruption on their clinical MPRAGE scans were prospectively enrolled. ResultsIn part (1), SAMER resulted in effective correction of motion-induced cortical volume and thickness reductions. We observed systematic increases in the estimated cortical volume and thickness across all neuroanatomical regions and a relative reduction in percent error values compared to reference standard scans of up to 66 % for the cerebral white matter volume. In part (2), SAMER resulted in statistically significant volume increases across anatomical regions, with the most pronounced increases seen in the parietal and temporal lobes, and general reductions in percent error relative to reference standard clinical scans. ConclusionSAMER improves the accuracy of morphometry through systematic increases and recovery of the estimated cortical volume and cortical thickness following motion correction, which may affect the evaluation of regional cortical atrophy in patients undergoing evaluation for dementia.

Characterization of Laboratory-Confirmed Creutzfeldt-Jakob Disease From 3 Ontario Tertiary Care Centers Between 2012 and 2022: A Retrospective Cohort Study.

Globally, Creutzfeldt-Jakob disease (CJD) affects one in one million people annually, but there is a paucity of recent Canadian data. This study summarizes epidemiology trends and diagnostic timelines of laboratory-confirmed CJD cases in three tertiary Ontario hospitals. Using laboratory information systems, we identified 30 patients with a laboratory-confirmed CJD diagnosis between 2012 and 2022 at three major tertiary hospitals in Ontario. Retrospective chart reviews were then completed. Patients had a mean of 2.2 hospital visits (SD, 1.2) prior to being admitted for testing. The most common symptom presentations included loss of coordination (63.3%), behavioral changes (60%), progressive mobility loss (53.4%), memory loss (50.0%), and involuntary movements (50.0%). Magnetic resonance imaging findings showed potential CJD in 76.7% of cases, and 56.7% exhibited periodic sharp wave complexes characteristic of CJD on electroencephalogram. The mean duration from symptom onset to microbiologic testing was 91 days (SD, 90.7). End-point quaking-induced conversion (EP-QuIC) testing of cerebrospinal fluid was positive in 90.0% of patients, while 83.3% tested positive for 14-3-3 on enzyme-linked immunosorbent assay. Elevated cerebrospinal fluid 14-3-3 levels significantly correlated with shorter duration from symptom onset to death (R 2 = 0.71, F = 19.55, P = .0022). Post-diagnosis, 46.7% of patients were discharged home, 16.6% were transferred to external palliative care or hospice facilities, and 36.7% died during admission. The mean time from symptom onset to death was 121 days (SD, 120.7), and from diagnosis to death 35 days (SD, 83.9). This study highlights the importance of early CJD consideration and laboratory testing when appropriate neurologic symptoms are present.

Predicting biological activity and design of 5-HT6 antagonists through assessment of ANN-QSAR models in the context of Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia around the world, totaling about 55 million cases, with an estimated growth to 74.7 million cases in 2030, which makes its treatment widely desired. Several studies and strategies are being developed considering the main theories regarding its origin since it is not yet fully understood. Among these strategies, the 5-HT6 receptor antagonism emerges as an auspicious and viable symptomatic treatment approach for AD. The 5-HT6 receptor belongs to the G protein-coupled receptor (GPCR) family and is closely implicated in memory loss processes. As a serotonin receptor, it plays an important role in cognitive function. Consequently, targeting this receptor presents a compelling therapeutic opportunity. By employing antagonists to block its activity, the 5-HT6 receptor's functions can be effectively modulated, leading to potential improvements in cognition and memory. Addressing this challenge, our research explored a promising avenue in drug discovery for AD, employing Artificial Neural Networks-Quantitative Structure-Activity Relationship (ANN-QSAR) models. These models have demonstrated great potential in predicting the biological activity of compounds based on their molecular structures. By harnessing the capabilities of machine learning and computational chemistry, we aimed to create a systematic approach for analyzing and forecasting the activity of potential drug candidates, thus streamlining the drug discovery process. We assembled a diverse set of compounds targeting this receptor and utilized density functional theory (DFT) calculations to extract essential molecular descriptors, effectively representing the structural features of the compounds. Subsequently, these molecular descriptors served as input for training the ANN-QSAR models alongside corresponding biological activity data, enabling us to predict the potential efficacy of novel compounds as 5-hydroxytryptamine receptor 6 (5-HT6) antagonists. Through extensive analysis and validation of ANN-QSAR models, we identified eight new promising compounds with therapeutic potential against AD.

A multimodal cross-transformer-based model to predict mild cognitive impairment using speech, language and vision

Mild Cognitive Impairment (MCI) is an early stage of memory loss or other cognitive ability loss in individuals who maintain the ability to independently perform most activities of daily living. It is considered a transitional stage between normal cognitive stage and more severe cognitive declines like dementia or Alzheimer’s. Based on the reports from the National Institute of Aging (NIA), people with MCI are at a greater risk of developing dementia, thus it is of great importance to detect MCI at the earliest possible to mitigate the transformation of MCI to Alzheimer’s and dementia. Recent studies have harnessed Artificial Intelligence (AI) to develop automated methods to predict and detect MCI. The majority of the existing research is based on unimodal data (e.g., only speech or prosody), but recent studies have shown that multimodality leads to a more accurate prediction of MCI. However, effectively exploiting different modalities is still a big challenge due to the lack of efficient fusion methods. This study proposes a robust fusion architecture utilizing an embedding-level fusion via a co-attention mechanism to leverage multimodal data for MCI prediction. This approach addresses the limitations of early and late fusion methods, which often fail to preserve inter-modal relationships. Our embedding-level fusion aims to capture complementary information across modalities, enhancing predictive accuracy. We used the I-CONECT dataset, where a large number of semi-structured conversations via internet/webcam between participants aged 75+ years old and interviewers were recorded. We introduce a multimodal speech-language-vision Deep Learning-based method to differentiate MCI from Normal Cognition (NC). Our proposed architecture includes co-attention blocks to fuse three different modalities at the embedding level to find the potential interactions between speech (audio), language (transcribed speech), and vision (facial videos) within the cross-Transformer layer. Experimental results demonstrate that our fusion method achieves an average AUC of 85.3% in detecting MCI from NC, significantly outperforming unimodal (60.9%) and bimodal (76.3%) baseline models. This superior performance highlights the effectiveness of our model in capturing and utilizing the complementary information from multiple modalities, offering a more accurate and reliable approach for MCI prediction.

Exploring Perceived Limitations to Daily Activities Due to Chronic Conditions: A Person-Centered Approach to Measuring Multimorbidity Severity.

Person-centered approaches to measuring severity of multimorbidity (≥ 2 chronic conditions) can help clinicians assess the individual experience of multimorbidity and inform effective caregiving and intervention strategies. We examine how limitations in everyday activities attributable to specific chronic conditions act independently and in tandem to influence individual perceptions of multimorbidity severity. Data from the Panel Study of Income Dynamics (2005-2021) were used to investigate self-reported limitations in normal daily activities resulting from nine chronic conditions (hypertension, arthritis, diabetes, heart condition [heart disease/heart attack], cancer, lung disease, stroke, depression, and memory loss) in 4,318 adults aged 55-95 (18,878 person-wave observations). We used descriptive and inferential analyses to estimate limitations resulting from specific conditions, limitations attributable to condition combinations, and the contribution of comorbid conditions to condition-specific and overall severity. Follow-up analyses addressed mortality selection using inverse probability weighting (IPW) and examined cancer type and cancer status/treatment modality among respondents reporting cancer diagnosis. Of the more prevalent conditions, arthritis was associated with the most severe limitations to normal activities. Memory loss was the least frequent condition reported, but resulted in the most severe limitations, and as a comorbid condition, increased limitations reported for most conditions. IPW adjusted models revealed heterogeneity in estimates for some conditions including cancer and cancer survivors tended to report less lethal cancers that were cured or in remission. Our results suggest that efforts to prevent and treat arthritis and support cognitive function may reduce the severity of multimorbidity experienced by the individual.

Phyto-nanotechnology: A novel beneficial strategy for Alzheimer's disease therapy

Alzheimer's disease, a neurodegenerative condition, is characterized by the slow and progressive deterioration of the cognitive functions of geriatric patients. It occurs due to exacerbation of neurons in the brain, indicated by loss of memory, mood instability, and even death. The aggregation of amyloid β protein and neurofibrillary tangles-atypical forms of tau protein is the major cause of this disease. Phytoconstituents have been frequently employed in treating Alzheimer's disease. These natural compounds act through different molecular mechanisms to treat the disease. However, their potential in Alzheimer's disease therapy may be limited due to poor blood-brain barrier permeability, off-target effects, low bioavailability, etc. In recent times, nanotechnology has gained attraction to overcome these challenges. This article focuses on the potential phytoconstituents for Alzheimer's disease treatment and the associated limitations. Moreover, it highlights various nanoformulation strategies employed to penetrate the blood-brain barrier effectively, avoid side effects, improve bioavailability, and target specificity in treating Alzheimer's disease. The integration of nanotechnology with plant-derived compounds has the potential to revolutionize the therapeutic landscape for Alzheimer's disease.

Safflower Improves Memory, Learning, and Behavior in Rats Subjected to Sleep Deprivation.

Sleep is a physiological process that provides the body with a window for recovery and restoration. Intriguingly, even short-term sleep deprivation can impair brain memory, emotional capacity, information processing, and attention. Safflower (Carthamus tinctorius L.) has been shown to attenuate memory loss and improve anxiety and depression. This study aims to study the possible therapeutic effect of safflower on sleep deprivation-dependent effects on memory and behavior. Thirty young male Wistar albino rats were acclimatized, trained, and then assigned to three random groups: control (C), sleep-deprived (SD), and sleep-deprived Safflower-treated (SD+Sf) groups. Morris Water Maze (MWM) and Elevated Plus Maze (EPM) tests were used to study spatial memory and learningand anxiety-related behavior, respectively, in the study groups. There was a significant deterioration in learning and memory, as tested by the MWM in the SD group, compared to the C group. This included prolonged test duration, reduced average speed, and longer travel distance. Treatment with safflower significantly improved MWM test performance in the SD+Sf group when compared to the SD group. When compared to the C group, rats in the SD group demonstrated altered EPM test parameters suggestive of anxiety-like behavior. These included spending more time in the closed arms, spending less time in the open arms, and having fewer entries in the open arms. Rats in the SD+Sf group showed improved EPM test parameters when compared to the SD group. Safflower significantly ameliorated sleep deprivation induced by memory loss and altered behavior. Safflower supplementation may provide potential memory-enhancing and preserving, anxiolytic, and antidepressant therapeutic roles.

Withania somnifera (Ashwagandha) Improves Spatial Memory, Anxiety and Depressive-like Behavior in the 5xFAD Mouse Model of Alzheimer's Disease.

Withania somnifera (WS), also known as ashwagandha, is a popular botanical supplement used to treat various conditions including memory loss, anxiety and depression. Previous studies from our group showed an aqueous extract of WS root (WSAq) enhances cognition and alleviates markers for depression in Drosophila. Here, we sought to confirm these effects in the 5xFAD mouse model of β-amyloid (Aβ) accumulation. Six- to seven-month-old male and female 5xFAD mice were treated with WSAq in their drinking water at 0 mg/mL, 0.5 mg/mL or 2.5 mg/mL for four weeks. In the fourth week of treatment, spatial memory, anxiety and depressive-like symptoms were evaluated. At the conclusion of behavioral testing, brain tissue was harvested, immunohistochemistry was performed, and the cortical expression of antioxidant response genes was evaluated. Both concentrations of WSAq improved spatial memory and reduced depressive and anxiety-related behavior. These improvements were accompanied by a reduction in Aβ plaque burden in the hippocampus and cortex and an attenuation of activation of microglia and astrocytes. Antioxidant response genes were upregulated in the cortex of WSAq-treated mice. Oral WSAq treatment could be beneficial as a therapeutic option in AD for improving disease pathology and behavioral symptoms. Future studies focused on dose optimization of WSAq administration and further assessment of the mechanisms by which WSAq elicits its beneficial effects will help inform the clinical potential of this promising botanical therapy.

Glucose Metabolic Abnormality: A Crosstalk between Depression and Alzheimer's Disease.

Depression and Alzheimer's disease (AD) are two prevalent and debilitating conditions that significantly impact millions of people worldwide. Depressive disorders are characterized by persistent feelings of sadness, loss of interest, and impaired cognitive function. AD is a progressive neurodegenerative disorder that is accompanied by cognitive decline, memory loss, and behavioral changes. To date, the pathogenesis of AD and depression has not yet been fully explained. Recent studies have provided insights into the intricate relationship between these two disorders by emphasizing the role of glucose metabolic abnormalities as a potential link. This review explores the bidirectional association between depression and AD, focusing on common pathophysiological mechanisms involving glucose metabolism, such as hypothalamic-pituitary-adrenal (HPA) axis dysregulation, insulin resistance, glucose transporters, and oxidative stress. Understanding the crosstalk between glucose metabolic abnormalities, depression, and AD will open new avenues for therapeutic interventions. Finally, improving glucose metabolism through lifestyle modifications, pharmaceutical interventions or novel therapeutic approaches could provide a promising therapeutic strategy for managing both conditions simultaneously.

Progress of research in the application of ultrasound technology for the treatment of Alzheimer's disease.

Alzheimer's disease is a common neurodegenerative disorder defined by decreased reasoning abilities, memory loss, and cognitive deterioration. The presence of the blood-brain barrier presents a major obstacle to the development of effective drug therapies for Alzheimer's disease. The use of ultrasound as a novel physical modulation approach has garnered widespread attention in recent years. As a safe and feasible therapeutic and drug-delivery method, ultrasound has shown promise in improving cognitive deficits. This article provides a summary of the application of ultrasound technology for treating Alzheimer's disease over the past 5 years, including standalone ultrasound treatment, ultrasound combined with microbubbles or drug therapy, and magnetic resonance imaging-guided focused ultrasound therapy. Emphasis is placed on the benefits of introducing these treatment methods and their potential mechanisms. We found that several ultrasound methods can open the blood-brain barrier and effectively alleviate amyloid-β plaque deposition. We believe that ultrasound is an effective therapy for Alzheimer's disease, and this review provides a theoretical basis for future ultrasound treatment methods.

A Mixed Methods Analysis of Long COVID Symptoms in Black Americans: Examining Physical and Mental Health Outcomes.

While several reports confirm that long COVID is associated with poorer health, few studies explore how long COVID directly impacts the lives of Black Americans who experienced higher mortality rates early in the pandemic. Even fewer studies utilize both quantitative and qualitative methods to identify pertinent long COVID symptoms. The current study, therefore, sought to identify points of overlap and divergence when comparing qualitative vs. quantitative descriptions of long COVID experiences among Black adults in the United States. We analyzedcross-sectional surveys collected from the AmeriSpeak panel through the National Opinion Research Center (NORC) at the University of Chicago. This panel includes a probability-based sample of adults across the UnitedStates. Respondents completed online surveys between April and June 2022. We compared outcomes among participants who reported experiencing post-acute sequelae of COVID-19 (i.e., long COVID) to those who reported experiencing SARS-CoV-2 without long COVID. Nearly all qualitative responses focused on matters of physical health like prolonged coughing, cardiovascular concerns, troubled breathing, fatigue, headaches, memory loss, and bodily pains. Quantitative results, however, showed that Black adults living with long COVID reported significantly more anxiety, depressive symptoms, and hopelessness. Persons with long COVID were also significantly more likely to report experiencing psychosis, suicidal ideation, suicide plans, and suicide attempts within the last year. Black adults with long COVID experienced worse outcomes across all mental health measures. Despite the COVID-19 Public Health Emergency expiration in May 2023, urgent efforts are still required to not only treat both the physical and mental health needs of persons living with long COVID, but to effectively prevent the spread and transmission of COVID-19.

Cognitive and Histopathological Alterations in Rat Models of Early- and Late-Phase Memory Dysfunction: Effects of Sigma-1 Receptor Activation.

Sigma-1 receptors are highly expressed in brain areas related to cognitive function and are a promising target for anti-amnesic treatments. We previously showed that activation of sigma-1 receptors by the selective agonist compound methyl(1 R,2 S/1 S,2 R)-2-[4-hydroxy-4-phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl) cyclopropane carboxylate [(±)-PPCC] promotes a remarkable recovery in rat models of memory loss associated to cholinergic dysfunction. In this study, we sought to assess the role of (±)-PPCC on working memory deficits caused by noradrenergic depletion. Animals with a mild or severe working memory deficits associated to varying degrees of noradrenergic neuronal depletion were treated with the sigma-1 agonist just prior to the beginning of each behavioral testing session. While (±)-PPCC alone at a dose of 1 mg/kg/day failed to affect working memory in lesioned animals, its association with the α2 adrenergic receptor agonist clonidine, completely blocked noradrenaline release, significantly improving rat performance. This effect, distinct from noradrenaline activity, is likely to result from a direct action of the (±)-PPCC compound onto sigma-1 receptors, as pre-treatment with the selective sigma-1 receptor antagonist BD-1047 reversed the improved working memory performance. Despite such clear functional effects, the treatment did not affect noradrenergic neuron survival or terminal fiber proliferation. Future studies are thus necessary to address the effects of long-lasting (±)-PPCC treatment, with or without clonidine, on cognitive abilities and Alzheimer's disease-like histopathology. Considering the already established involvement of sigma-1 receptors in endogenous cell plasticity mechanisms, their activation by selective agonist compounds holds promises as possibly positive contributor to disease-modifying events in neurodegenerative diseases.

Fibromyalgia progression and association with other diseases and inheritance with management practices in humans

Fibromyalgia is a widespread pain disorder characterized by chronic, diffuse pain, about 1 to 5% around world. While more prevalent in women and adults, it can also manifest in children and adolescents. The specific pathophysiology of fibromyalgia remains unclear, but it is associated with neuronal over sensitization, reduced conditioned pain modulation, cognitive dysfunction, memory loss, and impaired information processing. It has now been categorized as a somatic symptom disorder. This study aimed to investigate fibromyalgia, focusing on its potential hereditary connections and management practices. A key pathophysiological aspect of fibromyalgia is central sensitization, marked by increased functional connectivity with pre-receptive brain areas, decreased connectivity with antinociceptive areas, and alterations in central nervous system neurotransmitters, also in size and shape of specific brain areas. Fibromyalgia is not directly inherited from parents to offspring, it does exhibit a tendency to cluster within families. The serotonin transporter gene, characterized by single nucleotide polymorphism with "S" (short) allele, is more prevalent in individuals with fibromyalgia and psychological distress. In conclusion, fibromyalgia is a widespread pain disorder with a substantial impact on the central nervous system, resulting in significant disability and an elevated risk of chronic diseases. Early diagnosis and intervention can minimize the impact of fibromyalgia. Physical therapy and non-drug therapies should be customized for each patient. The FDA has approved three drugs including pregabalin, duloxetine, and milnacipran for fibromyalgia treatment.

Understanding Digital Dementia and Cognitive Impact in the Current Era of the Internet: A Review.

Dementia encompasses symptoms resulting from brain damage that impairs cognitive functions, surpassing natural aging effects. This condition affects emotional regulation, behavior, and motivation while preserving consciousness. Dr. Manfred Spitzer coined the term 'digital dementia,' highlighting the cognitive decline associated with excessive reliance on digital devices such as smartphones and Google, potentially exacerbating attention deficit hyperactivity disorder (ADHD) and memory loss. This condition mirrors terms like 'digital amnesia' and 'the Google Effect,' highlighting the brain's tendency to offload peripheral information, leading to panic and forgetfulness. Spitzer's book, Digital Dementia, focuses on gaming effects on children and has thus popularized the term. Teenagers are known to use electronic devices regularly, correlating with rising cognitive impairments. The advent of the internet's fifth generation (5G) has transformed technology use, impacting mental health treatments and clinical practices globally. Digital media's influence on the developing brain encompasses motor skills, language, and cognition. Excessive digital media use in young adults correlates with lower cognitive empathy, affecting interpersonal understanding and facial recognition. Studies link heavy reliance on web-based media to decreased white matter integrity, crucial for language skills. Adolescents may be more vulnerable to anxiety and unrealistic expectations due to digital media overuse. Digital media overuse impacts brain development, especially cognitive and inhibitory control, attention, memory, and reasoning, essential for adapting to dynamic environments. Early exposure to fast-paced media can impair motor skills, spatial awareness, problem-solving, and language learning. Neuroimaging studies reveal that environmental factors like screen usage affect brain networks controlling social-emotional behavior and executive functions. Overreliance on smartphones diminishes gray matter in key brain regions, affecting cognitive and emotional regulation. The internet generation, characterized by advancements such as Web 3.0, introduces artificial intelligence and semantic web technologies, reshaping digital content processing. The neurobiological basis of digital dementia involves changes in the brain structure and function, with excessive screen exposure linked to cognitive impairments. Neuroplasticity, or the brain's adaptability, plays a role in cognitive decline from digital media overuse. Early childhood and adolescent brain development stages exhibit significant plasticity, influencing cognitive trajectories. Addressing digital dementia requires strategies to reduce screen time, promote cognitive exercises, and enhance awareness. Parents should regulate children's screen usage, encourage digital detox periods, and substitute screen time with other activities. Cognitive training programs such as Cogmed (Neural Assembly Int AB, Stockholm, SWE) and CogniFit (San Francisco, CA, USA) can improve memory and attention in older adults. Promoting balanced technology use and educating on the risks of excessive digital media consumption is crucial for maintaining cognitive health in the digital age.

A meta-analysis of the effects of transcranial direct current stimulation combined with cognitive training on working memory in healthy older adults.

Working memory (WM) loss, which can lead to a loss of independence, and declines in the quality of life of older adults, is becoming an increasingly prominent issue affecting the ageing population. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, is emerging as a potential alternative to pharmacological treatments that shows promise for enhancing WM capacity and May enhance the effects of cognitive training (CT) interventions. The purpose of this meta-analysis was to explore how different tDCS protocols in combination with CT enhanced WM in healthy older adults. Randomized controlled trials (RCTs) exploring the effects of tDCS combined with CT on WM in healthy older adults were retrieved from the Web of Science, PubMed, Embase, Scopus and the Cochrane Library databases. The search time period ranged from database inception to January 15, 2024. Methodological quality of the trials was assessed using the risk-of-bias criteria for RCTs from the Cochrane Collaboration Network, and RevMan 5.3 (Cochrane, London, United Kingdom) was used for the meta-analysis of the final literature outcomes. Six RCTs with a total of 323 participants were ultimately included. The results of the meta-analysis show that tDCS combined with CT statistically significantly improves WM performance compared to the control sham stimulation group in healthy older adults [standard mean difference (SMD) = 0.35, 95% CI: 0.11-0.59, I 2 = 0%, Z = 2.86, p = 0.004]. The first subgroup analysis indicated that, when the stimulus intensity was 2 mA, a statistically significant improvement in WM performance in healthy older adults was achieved (SMD = 0.39, 95% CI: 0.08-0.70, I 2 = 6%, Z = 2.46, p = 0.01). The second subgroup analysis showed that long-term intervention (≥ 10 sessions) with tDCS combined with CT statistically significantly improved WM compared to the control group in healthy older adults (SMD = 0.72, 95% CI: 0.22-1.21, I 2 = 0%, Z = 2.85, p = 0.004). tDCS combined with CT statistically significantly improves WM in healthy older adults. For the stimulus parameters, long-term interventions (≥ 10 sessions) with a stimulation intensity of 2 mA are the most effective.

DMT1 knockout abolishes ferroptosis induced mitochondrial dysfunction in C. elegans amyloid β proteotoxicity

Iron is critical for neuronal activity and metabolism, and iron dysregulation alters these functions in age-related neurodegenerative disorders, such as Alzheimer's disease (AD). AD is a chronic neurodegenerative disease characterized by progressive neuronal dysfunction, memory loss and decreased cognitive function. AD patients exhibit elevated iron levels in the brain compared to age-matched non-AD individuals. However, the degree to which iron overload contributes to AD pathogenesis is unclear. Here, we evaluated the involvement of ferroptosis, an iron-dependent cell death process, in mediating AD-like pathologies in C. elegans. Results showed that iron accumulation occurred prior to the loss of neuronal function as worms age. In addition, energetic imbalance was an early event in iron-induced loss of neuronal function. Furthermore, the loss of neuronal function was, in part, due to increased mitochondrial reactive oxygen species mediated oxidative damage, ultimately resulting in ferroptotic cell death. The mitochondrial redox environment and ferroptosis were modulated by pharmacologic processes that exacerbate or abolish iron accumulation both in wild-type worms and worms with increased levels of neuronal amyloid beta (Aβ). However, neuronal Aβ worms were more sensitive to ferroptosis-mediated neuronal loss, and this increased toxicity was ameliorated by limiting the uptake of ferrous iron through knockout of divalent metal transporter 1 (DMT1). In addition, DMT1 knockout completely suppressed phenotypic measures of Aβ toxicity with age. Overall, our findings suggest that iron-induced ferroptosis alters the mitochondrial redox environment to drive oxidative damage when neuronal Aβ is overexpressed. DMT1 knockout abolishes neuronal Aβ−associated pathologies by reducing neuronal iron uptake.

On the lasting impact of mild traumatic brain injury on working memory: Behavioural and electrophysiological evidence

Despite increasing recognition of the significance of mild traumatic brain injury (mTBI), the long-term cognitive consequences of the injury remain unclear. More sensitive measures that can detect subtle cognitive changes and consideration of individual variability are needed to properly characterise cognitive outcomes following mTBI. Here, we used complex behavioural tasks, individual differences approaches, and electrophysiology to investigate the long-term cognitive effects of a history of mTBI. In Experiment 1, participants with self-reported mTBI history (n=82) showed poorer verbal working memory performance on the operation span task compared to control participants (n=88), but there were no group differences in visual working memory, multitasking, cognitive flexibility, attentional control, visuospatial ability, or information processing speed. Individual differences analyses revealed that time since injury and presence of memory loss predicted visual working memory capacity and visuospatial ability, respectively, in those with mTBI history. In Experiment 2, participants with mTBI history (n=20) again demonstrated poorer verbal working memory on the operation span task compared to control participants (n=38), but no group differences were revealed on a visuospatial complex span task or simpler visual working memory measures. We also explored the electrophysiological indices of visual working memory using EEG during a change detection task. No differences were observed in early sensory event-related potentials (P1, N1) or the later negative slow wave associated with visual working memory capacity. Together, these findings suggest that mTBI history may be associated with a lasting, isolated disruption in the subsystem underlying verbal working memory storage. The results emphasise the importance of sensitive cognitive measures and accounting for individual variability in injury characteristics when assessing mTBI outcomes.

Memory problems in elderly people with traumatic brain injury

AbstractThe aim of this study is to assess the effectiveness of various therapy methods in elderly individuals with traumatic brain injury (TBI), taking into account the degree of memory loss and the severity of the injury. The study was conducted in 2022 in Moscow, Russia, and Sofia, Bulgaria, involving six clinics. A total of 200 elderly patients with TBI participated in the study, with a mean age of 72 years. Patients were categorized into groups based on the degree of memory loss and severity of the injury. Standardized tests, including the Mini‐Mental State Examination (MMSE), Clock Drawing Test, Digit Symbol Substitution Test, and Free, and Cued Selective Reminding Test, were used to assess cognitive functions. The Progressive Learning Test evaluated patients' ability to memorize and reproduce information over time. Groups receiving physical therapy and cognitive rehabilitation showed statistically significant improvement in cognitive functions compared to other therapy methods. Specifically, the mean score of the MMSE in these groups increased by 7 points (p < .001). Patients with more severe memory loss demonstrated more pronounced improvement in cognitive functions following the integrated therapy approach. The mean MMSE score increased by 10 points (p < .001), whereas in patients with milder memory loss, the growth was less significant (mean increase of 5 points, p < .05). Groups receiving physical therapy and cognitive rehabilitation consistently demonstrated significantly better results compared to speech therapy and psychological support throughout the study period.

Degeneración combinada subaguda de la médula y gastritis atrófica: revisión de la literatura

Introduction: Subacute combined degeneration of the spinal cord is a consequence of vitamin B12 deficiency. Its clinical presentation includes paresthesia, and proprioception and vibratory sensation loss, which can become disabling. Case presentation: we report the case of an elderly patient who experienced initial paresthesia which progressed to paraparesis, as well as some memory loss. Based on his physical examination a diagnostic impression of myelitis was made. Further investigation evidenced cyanocobalamin deficiency. Conclusion: patient was treated with vitamin B12 supplementation, obtaining an adequate response. There are numerous causes of vitamin B12 deficiency, however, its treatment is simple, and its early initiation can prevent severe neurological symptoms leading to disability.

Exploring the Role of Reactive Oxygen Species in the Pathogenesis and Pathophysiology of Alzheimer's and Parkinson's Disease and the Efficacy of Antioxidant Treatment.

Alzheimer's (AD) and Parkinson's Disease (PD) are life-altering diseases that are characterised by progressive memory loss and motor dysfunction. The prevalence of AD and PD is predicted to continuously increase. Symptoms of AD and PD are primarily mediated by progressive neuron death and dysfunction in the hippocampus and substantia nigra. Central features that drive neurodegeneration are caspase activation, DNA fragmentation, lipid peroxidation, protein carbonylation, amyloid-β, and/or α-synuclein formation. Reactive oxygen species (ROS) increase these central features. Currently, there are limited therapeutic options targeting these mechanisms. Antioxidants reduce ROS levels by the induction of antioxidant proteins and direct neutralisation of ROS. This review aims to assess the effectiveness of antioxidants in reducing ROS and neurodegeneration. Antioxidants enhance major endogenous defences against ROS including superoxide dismutase, catalase, and glutathione. Direct neutralisation of ROS by antioxidants protects against ROS-induced cytotoxicity. The combination of Indirect and direct protective mechanisms prevents ROS-induced α-synuclein and/or amyloid-β formation. Antioxidants ameliorate ROS-mediated oxidative stress and subsequent deleterious downstream effects that promote apoptosis. As a result, downstream harmful events including neuron death, dysfunction, and protein aggregation are decreased. The protective effects of antioxidants in human models have yet to directly replicate the success seen in cell and animal models. However, the lack of diversity in antioxidants for clinical trials prevents a definitive answer if antioxidants are protective. Taken together, antioxidant treatment is a promising avenue in neurodegenerative disease therapy and subsequent clinical trials are needed to provide a definitive answer on the protective effects of antioxidants. No current treatment strategies have significant impact in treating advanced AD and PD, but new mimetics of endogenous mitochondrial antioxidant enzymes (Avasopasem Manganese, GC4419 AVA) may be a promising innovative option for decelerating neurodegenerative progress in the future at the mitochondrial level of OS.