Memory Loss Research Articles

Characterizing dysregulations via cell-cell communications in Alzheimer’s brains using single-cell transcriptomes

BackgroundAlzheimer’s disease (AD) is a devastating neurodegenerative disorder affecting 44 million people worldwide, leading to cognitive decline, memory loss, and significant impairment in daily functioning. The recent single-cell sequencing technology has revolutionized genetic and genomic resolution by enabling scientists to explore the diversity of gene expression patterns at the finest resolution. Most existing studies have solely focused on molecular perturbations within each cell, but cells live in microenvironments rather than in isolated entities. Here, we leveraged the large-scale and publicly available single-nucleus RNA sequencing in the human prefrontal cortex to investigate cell-to-cell communication in healthy brains and their perturbations in AD. We uniformly processed the snRNA-seq with strict QCs and labeled canonical cell types consistent with the definitions from the BRAIN Initiative Cell Census Network. From ligand and receptor gene expression, we built a high-confidence cell-to-cell communication network to investigate signaling differences between AD and healthy brains.ResultsSpecifically, we first performed broad communication pattern analyses to highlight that biologically related cell types in normal brains rely on largely overlapping signaling networks and that the AD brain exhibits the irregular inter-mixing of cell types and signaling pathways. Secondly, we performed a more focused cell-type-centric analysis and found that excitatory neurons in AD have significantly increased their communications to inhibitory neurons, while inhibitory neurons and other non-neuronal cells globally decreased theirs to all cells. Then, we delved deeper with a signaling-centric view, showing that canonical signaling pathways CSF, TGFβ, and CX3C are significantly dysregulated in their signaling to the cell type microglia/PVM and from endothelial to neuronal cells for the WNT pathway. Finally, after extracting 23 known AD risk genes, our intracellular communication analysis revealed a strong connection of extracellular ligand genes APP, APOE, and PSEN1 to intracellular AD risk genes TREM2, ABCA1, and APP in the communication from astrocytes and microglia to neurons.ConclusionsIn summary, with the novel advances in single-cell sequencing technologies, we show that cellular signaling is regulated in a cell-type-specific manner and that improper regulation of extracellular signaling genes is linked to intracellular risk genes, giving the mechanistic intra- and inter-cellular picture of AD.

Improvement of both human and animal memory by synergy between fructooligosaccharide and L‐theanine function establishing a safe and effective food supplement

AbstractAging is classically associated with a decline of cognitive abilities, especially in relation to memory. While the development of potential treatments for neurodegenerative diseases has been in sharp focus, mild cognitive impairment (MCI), a form of age‐related memory loss, in the absence of severe functional impairment, a condition experienced by many healthy adults, has received relatively little attention. Advances in this space would make significant contributions to the goal of healthy aging and may also help promote cognitive performance across the wider population. The individual action of either fructooligosaccharide (FOS) or L‐theanine, both natural plant‐derived molecules, has been tentatively linked with improvements in cognition, but our understanding remains far from complete. We therefore determined the effect of different dose combinations of FOS and L‐theanine (termed MT‐01/GBL‐Memory1) in mice against FOS and L‐theanine monotherapy. FOS and L‐theanine were found to synergistically enhance murine memory in our animal tests at a dose of 100 mg/kg (coefficient of drug interaction (CDI) < 1). In a subsequent human trial, we demonstrated that MT‐01 improved the memory of healthy adults after 1 month of consumption. Our results suggest that a combination of FOS and L‐theanine synergistically enhances murine memory within a specific dose range. We show that this plant natural product regimen also improves human memory in a population of healthy adults. MT‐01 therefore represents a novel, safe, and effective dietary supplement to promote human memory and cognition.

Beneficial Effects of Echinacoside on Cognitive Impairment and Diabetes in Type 2 Diabetic db/db Mice.

Cognitive dysfunction is an important comorbidity of diabetes. Insulin resistance may play a critical role in diabetes-related cognitive impairment. Echinacoside (ECH), a natural phenylethanoid glycoside, is the active component of anti-diabetes prescriptions in traditional Chinese medicine. Its effect on modulating insulin resistance has been confirmed but modulating neurodegenerative disease remains unclear. Db/db mice, a spontaneous type 2 diabetes mode, were intragastrically administered ECH by 300 mg/kg or an equivalent volume of saline. Weight, blood glucose, and insulin resistance index were measured. Morris water maze test was performed to observe the compound effects on cognition. Hippocampal lesions were observed by histochemical analysis. In db/db mice, ECH alleviated diabetes symptoms, memory loss, and hippocampal neuronal damage. Next, the expression of CD44 and phosphorylated tau was upregulated in diabetic mice. In addition, the insulin receptor substrate-1/phosphatidylinositol 3-kinase /protein kinase B signaling pathway was dysregulated in diabetic mice. All these dysregulations could be reversed by ECH. This study provides theoretical support and experimental evidence for the future application of ECH in diabetic cognition dysfunction treatment, promoting the development of traditional medicines.

Antiviral, anti-inflammatory and antioxidant effects of curcumin and curcuminoids in SH-SY5Y cells infected by SARS-CoV-2

COVID-19, caused by SARS-CoV-2, affects neuronal cells, causing several symptoms such as memory loss, anosmia and brain inflammation. Curcuminoids (Me08 e Me23) and curcumin (CUR) are derived from Curcuma Longa extract (EXT). Many therapeutic actions have been linked to these compounds, including antiviral action. Given the severe implications of COVID-19, especially within the central nervous system, our study aims to shed light on the therapeutic potential of curcuminoids against SARS-CoV-2 infection, particularly in neuronal cells. Here, we investigated the effects of CUR, EXT, Me08 and Me23 in human neuroblastoma SH-SY5Y. We observed that Me23 significantly decreased the expression of plasma membrane-associated transmembrane protease serine 2 (TMPRSS2) and TMPRSS11D, consequently mitigating the elevated ROS levels induced by SARS-CoV-2. Furthermore, Me23 exhibited antioxidative properties by increasing NRF2 gene expression and restoring NQO1 activity following SARS-CoV-2 infection. Both Me08 and Me23 effectively reduced SARS-CoV-2 replication in SH-SY5Y cells overexpressing ACE2 (SH-ACE2). Additionally, all of these compounds demonstrated the ability to decrease proinflammatory cytokines such as IL-6, TNF-α, and IL-17, while Me08 specifically reduced INF-γ levels. Our findings suggest that curcuminoid Me23 could serve as a potential agent for mitigating the impact of COVID-19, particularly within the context of central nervous system involvement.

Memory protective effect of Phyllanthus emblica against scopolamine induced spatial memory loss in male Long Evan Rats tested by Radial Arm Maze

Background: Dementia is the commonest problem of middle aged and elderly subjects due to age related changes and oxidative stress. Many traditional herbal agents including Emblica Officinalis (Phyllantus Emblica) demonstrated its benefit against memory loss. Objective: To investigate the protective effect of Ethanolic extract of Phyllantus Emblica (EEPE) or Emblica Officinalis in scopolamine induced memory impaired male Long Evan rats. Methods: This animal behavioral study was carried out on total 18 male long Evan rats weighing 300-400gm. According to treatment they were divided into NS (control) group (n=6, normal saline 5ml/kg) Sco(n=6; Scopolamine 2mg/kg) and PE(n=6; EEPE 400mg/kg+ Scopolamine 2mg/kg).This experiment was conducted for total 33 days. After 7 days acclimatization NS group and PE rats were treated with normal saline and EEPE respectively for consecutive 26 days. Scopolamine was given to sco group and PE group from day 22 to 26 (5 days during acquisition phase. Spatial memory (working and reference memory error) was assessed by 8 arm radial arm maze (RAM). Statistical analysis was done by ANOVA followed by Bonferroni’s post hoc test. Result: Working memory error (WME) as well as reference memory error (RME) was found significantly higher in scopolamine treated rats compared to normal memory as well as PE pretreated rats whereas no significant difference was found in WME and RME between normal memory rats and PE pre- treated rats. Conclusion: Phyllanthus Emblica can prevent memory impairment in scopolamine induced memory loss in Long Evan rats. J Bangladesh Soc Physiol 2022;17(2): 101-110

Assessing the Quality of ChatGPT Responses to Dementia Caregivers' Questions: Qualitative Analysis.

Artificial intelligence (AI) such as ChatGPT by OpenAI holds great promise to improve the quality of life of patients with dementia and their caregivers by providing high-quality responses to their questions about typical dementia behaviors. So far, however, evidence on the quality of such ChatGPT responses is limited. A few recent publications have investigated the quality of ChatGPT responses in other health conditions. Our study is the first to assess ChatGPT using real-world questions asked by dementia caregivers themselves. This pilot study examines the potential of ChatGPT-3.5 to provide high-quality information that may enhance dementia care and patient-caregiver education. Our interprofessional team used a formal rating scale (scoring range: 0-5; the higher the score, the better the quality) to evaluate ChatGPT responses to real-world questions posed by dementia caregivers. We selected 60 posts by dementia caregivers from Reddit, a popular social media platform. These posts were verified by 3 interdisciplinary dementia clinicians as representing dementia caregivers' desire for information in the areas of memory loss and confusion, aggression, and driving. Word count for posts in the memory loss and confusion category ranged from 71 to 531 (mean 218; median 188), aggression posts ranged from 58 to 602 words (mean 254; median 200), and driving posts ranged from 93 to 550 words (mean 272; median 276). ChatGPT's response quality scores ranged from 3 to 5. Of the 60 responses, 26 (43%) received 5 points, 21 (35%) received 4 points, and 13 (22%) received 3 points, suggesting high quality. ChatGPT obtained consistently high scores in synthesizing information to provide follow-up recommendations (n=58, 96%), with the lowest scores in the area of comprehensiveness (n=38, 63%). ChatGPT provided high-quality responses to complex questions posted by dementia caregivers, but it did have limitations. ChatGPT was unable to anticipate future problems that a human professional might recognize and address in a clinical encounter. At other times, ChatGPT recommended a strategy that the caregiver had already explicitly tried. This pilot study indicates the potential of AI to provide high-quality information to enhance dementia care and patient-caregiver education in tandem with information provided by licensed health care professionals. Evaluating the quality of responses is necessary to ensure that caregivers can make informed decisions. ChatGPT has the potential to transform health care practice by shaping how caregivers receive health information.

Differential disruptions in population coding along the dorsal-ventral axis of CA1 in the APP/PS1 mouse model of Aβ pathology.

Alzheimer's Disease (AD) is characterized by a range of behavioral alterations, including memory loss and psychiatric symptoms. While there is evidence that molecular pathologies, such as amyloid beta (Aβ), contribute to AD, it remains unclear how this histopathology gives rise to such disparate behavioral deficits. One hypothesis is that Aβ exerts differential effects on neuronal circuits across brain regions, depending on the neurophysiology and connectivity of different areas. To test this, we recorded from large neuronal populations in dorsal CA1 (dCA1) and ventral CA1 (vCA1), two hippocampal areas known to be structurally and functionally diverse, in the APP/PS1 mouse model of amyloidosis. Despite similar levels of Aβ pathology, dCA1 and vCA1 showed distinct disruptions in neuronal population activity as animals navigated a virtual reality environment. In dCA1, pairwise correlations and entropy, a measure of the diversity of activity patterns, were decreased in APP/PS1 mice relative to age-matched C57BL/6 controls. However, in vCA1, APP/PS1 mice had increased pair-wise correlations and entropy as compared to age matched controls. Finally, using maximum entropy models, we connected the microscopic features of population activity (correlations) to the macroscopic features of the population code (entropy). We found that the models' performance increased in predicting dCA1 activity, but decreased in predicting vCA1 activity, in APP/PS1 mice relative to the controls. Taken together, we found that Aβ exerts distinct effects across different hippocampal regions, suggesting that the various behavioral deficits of AD may reflect underlying heterogeneities in neuronal circuits and the different disruptions that Aβ pathology causes in those circuits.

Utilizing Profound Learning Methods for Alzheimer's Infection Discovery: An Exhaustive Survey

Alzheimer’s disease (AD) is a major public health issue around the world. It is a progressive disease that causes memory loss and cognitive decline. Early detection is essential for early intervention and treatment of AD. In recent years, there has been a surge in the use of deep learning techniques to analyze complex medical data. This includes neuroimaging data as well as genetic data. This has led to promising advances in the detection of AD. In this paper, we will review the application of various deep learning methods in the field of Alzheimer’s Disease. We will look at the challenges that traditional diagnostic methods face and how these challenges can be overcome by using deep learning approaches. We will also look at different deep learning architectures and data modalities and techniques used in the field of AD detection. Finally, we will look at limitations and future direction of the field to help researchers and practitioners to develop more accurate and effective AD detection methods. Keywords: Alzheimer's Disease, deep learning, neuroimaging, biomarkers, early detection, diagnosis.

Tracts in the limbic system show microstructural alterations post COVID-19 recovery.

Delirium, memory loss, attention deficit and fatigue are frequently reported by COVID survivors, yet the neurological pathways underlying these symptoms are not well understood. To study the possible mechanisms for these long-term sequelae after COVID-19 recovery, we investigated the microstructural properties of white matter in Indian cohorts of COVID-recovered patients and healthy controls. For the cross-sectional study presented here, we recruited 44 COVID-recovered patients and 29 healthy controls in New Delhi, India. Using deterministic whole-brain tractography on the acquired diffusion MRI scans, we traced 20 white matter tracts and compared fractional anisotropy, axial, mean and radial diffusivity between the cohorts. Our results revealed statistically significant differences (PFWE < 0.01) in the uncinate fasciculus, cingulum cingulate, cingulum hippocampus and arcuate fasciculus in COVID survivors, suggesting the presence of microstructural abnormalities. Additionally, in a subsequent subgroup analysis based on infection severity (healthy control, non-hospitalized patients and hospitalized patients), we observed a correlation between tract diffusion measures and COVID-19 infection severity. Although there were significant differences between healthy controls and infected groups, we found no significant differences between hospitalized and non-hospitalized COVID patients. Notably, the identified tracts are part of the limbic system and orbitofrontal cortex, indicating microstructural differences in neural circuits associated with memory and emotion. The observed white matter alterations in the limbic system resonate strongly with the functional deficits reported in Long COVID. Overall, our study provides additional evidence that damage to the limbic system could be a neuroimaging signature of Long COVID. The findings identify targets for follow-up studies investigating the long-term physiological and psychological impact of COVID-19.

The WALLET Study: Financial Decision Making and Key Financial Behaviors Associated with Excess Spending

ABSTRACT Objectives The Wealth Accumulation and Losses in Later life Early Cognitive Transitions (WALLET) study data was used to examine correlates with excess spending in older adults who do and do not have early memory loss. Methods The WALLET study collected detailed financial information from participants’ primary checking account statements (n = 150). Information on participant sociodemographic, health, and disability status, memory functioning, financial decision-making, and financial literacy was also collected. Participants either had no memory problems or early memory loss. Bivariate and multiple regression analyses were conducted. Results The early memory loss group had significantly higher excess spending than those with no memory loss. Financial decision-making and higher-risk financial behaviors were also linked to higher excess spending. Early memory loss was no longer statistically significant after accounting for financial stressors and resources. Conclusions The multidimensional nature of financial capacity assessment has long been known. The WALLET study data is unique, however, in that it demonstrates the links between excess spending with decision-making, early memory loss, and a set of specific financial behaviors. Clinical Implications Real-world assessments of financial management and financial decision-making yield important information about how older adults are managing money and making key financial decisions. Checking account reviews can be used to determine excess spending.

Hesperidin neuroprotective effects against carbon monoxide-induced toxicity in male rats.

Carbon monoxide (CO) is produced via incomplete combustion of fossil fuels and it may cause long-term neurological sequel upon exposure. Hesperidin (HES), a flavanone glycoside found in citrus plants, exerts diverse beneficial health effects. The present study mechanistically examined the neuroprotective effects of HES in CO-poisoned rats. Thirty male Wistar rats (five groups of six animals) were exposed to 3000 ppm CO for 1 h. Immediately after the exposure and on the next 4 consecutive days (totally five doses), rats intraperitoneally received either normal saline (the control group) or different doses of HES (25, 50, and 100 mg/kg). A sham group that was not exposed to CO was also considered. After evaluation of spatial learning and memory using a Morris water maze (MWM), animals were sacrificed and oxidative stress status in blood samples, and Akt, Bax, Bcl2, and brain-derived neurotrophic factor (BDNF) expression in brain samples were assessed. Western blot analysis indicated increased Akt but decreased Bax/Bcl2 levels in the HES 100 mg/kg, and induced BDNF levels in all HES-treated groups. MWM results showed that HES significantly decreased memory loss. The current findings indicate that HES could alleviate neurological impairments induced by CO in rats.

Intervention modalities for brain fog caused by long-COVID: systematic review of the literature.

Individuals suffering from long-COVID can present with "brain fog", which is characterized by a range of cognitive impairments, such as confusion, short-term memory loss, and difficulty concentrating. To date, several potential interventions for brain fog have been considered. Notably, no systematic review has comprehensively discussed the impact of each intervention type on brain fog symptoms. We included studies on adult (aged > 18years) individuals with proven long- COVID brain-fog symptoms from PubMed, MEDLINE, Central, Scopus, and Embase. A search limit was set for articles published between 01/2020 and 31/12/2023. We excluded studies lacking an objective assessment of brain fog symptoms and patients with preexisting neurological diseases that affected cognition before COVID-19 infection. This review provided relevant information from 17 studies. The rehabilitation studies utilized diverse approaches, leading to a range of outcomes in terms of the effectiveness of the interventions. Six studies described noninvasive brain stimulation, and all showed improvement in cognitive ability. Three studies described hyperbaric oxygen therapy, all of which showed improvements in cognitive assessment tests and brain perfusion. Two studies showed that the use of Palmitoylethanolamide and Luteolin (PEA-LUT) improved cognitive impairment. Noninvasive brain stimulation and hyperbaric oxygen therapy showed promising results in the treatment of brain fog symptoms caused by long-COVID, with improved perfusion and cortical excitability. Furthermore, both rehabilitation strategies and PEA-LUT administration have been associated with improvements in symptoms of brain fog. Future studies should explore combinations of interventions and include longer follow-up periods to assess the long-term effects of these treatments.

Abstract PO1-20-10: Wernicke Encephalopathy Syndrome in Metastatic Breast Cancer – A Diagnostic Dilemma or An Underdiagnosed Entity

Abstract Wernicke encephalopathy (WE) is an acute medical syndrome that manifests as a clinical triad of encephalopathy, gait ataxia, and oculomotor dysfunction, requiring urgent treatment. Early recognition and treatment can prevent severe neurological morbidity and the chronic neurological consequence of WE, known as Korsakoff syndrome. Thiamine (vitamin B1) deficiency is the root cause of WE, which can occur due to several underlying conditions, including chronic alcoholism, hyperemesis of pregnancy, malnutrition, prolonged fasting, and malignancy. In cases of malignancy, WE is often undiagnosed or misdiagnosed because the presenting symptoms can be confused with several other complications of malignancy. We present the case of a 47-year-old woman with no significant medical history who was diagnosed with triple negative metastatic breast cancer and admitted to the hospital with confusion, memory loss, and progressive lower extremity weakness. During her breast cancer treatments, she experienced significant nausea and vomiting, leading to a prolonged state of nutritional imbalance. Patient underwent extensive infectious and neurological workup for encephalopathy including lumbar puncture which was negative for leptomeningeal disease or infection. MRI brain did not show any new metastatic lesions however revealed enhancement of mammillary bodies bilaterally. Mammillary body enhancement can be seen in WE but not always present on imaging. She was treated for WE with high dose of thiamine infusion for five days, resulting in an improvement of her neurological symptoms. Diagnosing WE in cancer patients is challenging, as there are various factors to consider, such as cerebral metastasis, infection, chemotherapy treatment, and electrolyte imbalances, that can cause neurological symptoms. Cancer patients are at high risk for development of WE due to chemotherapy or whole brain radiation induced nausea and vomiting that can lead to chronic malnutrition. The typical triad of symptoms is not present in many cases and presenting symptoms can be nonspecific which makes the diagnosis challenging. As a result, WE is often underdiagnosed in such patients, making it essential to educate the physician community about this acute neurological manifestation that can be easily treated. A high index of suspicion is necessary for early recognition, and prompt treatment can prevent Korsakoff syndrome, thereby enhancing the overall quality of life of patients with malignancy. Citation Format: Archit Patel, Arya Mariam Roy, Ronald Alberico, Shipra Gandhi. Wernicke Encephalopathy Syndrome in Metastatic Breast Cancer – A Diagnostic Dilemma or An Underdiagnosed Entity [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-20-10.

Brain-targeted Tet-1 peptide-PLGA nanoparticles for berberine delivery against STZ-induced Alzheimer’s disease in a rat model: Alleviation of hippocampal synaptic dysfunction, Tau pathology, and amyloidogenesis

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder that causes severe dementia and memory loss. Surface functionalized poly(lactic-co-glycolic acid) nanoparticles have been reported for better transport through the blood–brain barrier for AD therapy. This study investigated the improved therapeutic potential of berberine-loaded poly(lactic-co-glycolic acid)/Tet-1 peptide nanoparticles (BBR/PLGA-Tet NPs) in a rat model of sporadic AD. BBR was loaded into the PLGA-Tet conjugate. BBR/PLGA-Tet NPs were physicochemically and morphologically characterized. AD was achieved by bilateral intracerebroventricular (ICV) injection of streptozotocin (STZ). Cognitively impaired rats were divided into STZ, STZ + BBR, STZ + BBR/PLGA-Tet NPs, and STZ + PLGA-Tet NPs groups. Cognitive improvement was assessed using the Morris Water Maze. Brain acetylcholinesterase and monoamine oxidase activities, amyloid β42 (Aβ42), and brain glycemic markers were estimated. Further, hippocampal neuroplasticity (BDNF, pCREB, and pERK/ERK), Tau pathogenesis (pGSK3β/GSK3β, Cdk5, and pTau), inflammatory, and apoptotic markers were evaluated. Finally, histopathological changes were monitored. ICV-STZ injection produces AD-like pathologies evidenced by Aβ42 deposition, Tau hyperphosphorylation, impaired insulin signaling and neuroplasticity, and neuroinflammation. BBR and BBR/PLGA-Tet NPs attenuated STZ-induced hippocampal damage, enhanced cognitive performance, and reduced Aβ42, Tau phosphorylation, and proinflammatory responses. BBR/PLGA-Tet NPs restored neuroplasticity, cholinergic, and monoaminergic function, which are critical for cognition and brain function. BBR/PLGA-Tet NPs may have superior therapeutic potential in alleviating sporadic AD than free BBR due to their bioavailability, absorption, and brain uptake.

Microglia-targeted inhibition of miR-17 via mannose-coated lipid nanoparticles improves pathology and behavior in a mouse model of Alzheimer’s disease

Neuroinflammation and accumulation of Amyloid Beta (Aβ) accompanied by deterioration of special memory are hallmarks of Alzheimer’s disease (AD). Effective preventative and treatment options for AD are still needed. Microglia in AD brains are characterized by elevated levels of microRNA-17 (miR-17), which is accompanied by defective autophagy, Aβ accumulation, and increased inflammatory cytokine production. However, the effect of targeting miR-17 on AD pathology and memory loss is not clear. To specifically inhibit miR-17 in microglia, we generated mannose-coated lipid nanoparticles (MLNPs) enclosing miR-17 antagomir (Anti-17 MLNPs), which are targeted to mannose receptors readily expressed on microglia. We used a 5XFAD mouse model (AD) that recapitulates many AD-related phenotypes observed in humans. Our results show that Anti-17 MLNPs, delivered to 5XFAD mice by intra-cisterna magna injection, specifically deliver Anti-17 to microglia in vivo and in vitro. Anti-17 MLNPs downregulated miR-17 expression in microglia but not in neurons, astrocytes, and oligodendrocytes. Anti-17 MLNPs attenuated inflammation, improved autophagy, and reduced Aβ burdens in the brains. Additionally, Anti-17 MLNPs reduced the deterioration in spatial memory and decreased anxiety-like behavior in 5XFAD mice. Therefore, targeting miR-17 using MLNPs is a viable strategy to prevent several AD pathologies. This selective targeting strategy delivers specific agents to microglia without the adverse off-target effects on other cell types. Additionally, this approach can be used to deliver other molecules to microglia and other immune cells in other organs.

Robot-Based Solution for Helping Alzheimer Patients

Alzheimer's is a progressive and debilitating neurological disorder characterized by cognitive decline, memory loss, and impaired daily functioning. It is an irreversible brain disease that destroys memory, thinking, and the ability to carry out daily activities. It poses significant challenges for patients and healthcare providers. Modern societies are trying to enhance the quality of people's lives, including Alzheimer's patients. In this study, we explored the potential of social robots to provide emotional support, improve cognitive function, and facilitate communication among Alzheimer's patients. This was achieved by initiating conversations on various topics such as family, relationships, and daily activities. This paper contributes to the literature by introducing a novel and well-organized framework for building an Alzheimer's care robot. Further, this study enriches the literature by introducing the Alzheimer Care Companion Robot (ACCR), designed to identify Alzheimer's patients. The ACCR initiates conversations in the native Arab-Kuwaiti dialect, displaying relevant memories through images and videos on its screen to assist in memory recall based on the individuals' life experiences. The proposed ACCR consists of 271 conversations belonging to three main categories: active, proactive, and graphical user interface (GUI) dialogs comprising 112 dialogs, 109 dialogs, and 50 dialogs for active, proactive, and GUI, respectively. The experimental result illustrated the success of the proposed solution.

Penthorum chinense Pursh inhibits ferroptosis in cellular and Caenorhabditis elegans models of Alzheimer's disease

Background: Ferroptosis, a unique type of cell death triggered by iron-dependent lipid peroxidation, plays a critical role in the pathogenesis of Alzheimer's disease (AD), a debilitating condition marked by memory loss and cognitive impairment due to the accumulation of beta-amyloid (Aβ) and hyperphosphorylated Tau protein. Increasing evidence suggests that inhibitors of ferroptosis could be groundbreaking in the treatment of AD. Method: In this study, we established in vitro ferroptosis using erastin-, RSL-3-, hemin-, and iFSP1-induced PC-12 cells. Using MTT along with Hoechst/PI staining, we assessed cell viability and death. To determine various aspects of ferroptosis, we employed fluorescence probes, including DCFDA, JC-1, C11 BODIPY, Mito-Tracker, and PGSK, to measure ROS production, mitochondrial membrane potential, lipid peroxidation, mitochondrial morphology, and intracellular iron levels. Additionally, Western blotting, biolayer interferometry technology, and shRNA were utilized to investigate the underlying molecular mechanisms. Furthermore, p-CAX APP Swe/Ind- and pRK5-EGFP-Tau P301L overexpressing PC-12 cells, along with Caenorhabditis elegans (C. elegans) strains CL4176, CL2331, and BR5270, were employed to examine ferroptosis in AD models. Results: Here, we conducted a screening of our natural medicine libraries and identified the ethanol extract of Penthorum chinense Pursh (PEE), particularly its ethyl acetate fraction (PEF), displayed inhibitory effects on ferroptosis in cells. Specifically, PEF inhibited the generation of ROS, lipid peroxidation, and intracellular iron levels. Furthermore, PEF demonstrated protective effects against H2O2-induced cell death, ROS production, and mitochondrial damage. Mechanistic investigations unveiled PEF's modulation of intracellular iron accumulation, GPX4 expression and activity, and FSP1 expression. In p-CAX APP Swe/Ind and pRK5-EGFP-Tau P301L overexpressing PC-12 cells, PEF significantly reduced cell death, as well as ROS and lipid peroxidase production. Moreover, PEF ameliorated paralysis and slowing rate in Aβ and Tau transgenic C. elegans models, while inhibiting ferroptosis, as evidenced by decreased DHE intensity, lipid peroxidation levels, iron accumulation, and expression of SOD-3 and gst-4. Conclusion: Our findings highlight the suppressive effects of PEF on ferroptosis in AD cellular and C. elegans models. This study helps us better understand how ferroptosis affects AD and emphasizes the potential of PCP as a candidate for AD intervention.

Incidence and risk factors of post COVID-19 syndrome: a Tunisian cohort study.

It has become increasingly clear that SARS-CoV-2 infection can lead to persistent physical and mental health problems lasting weeks or months, requiring prolonged periods of clinical care and increasing the burden on the healthcare system. This phenomenon, known as post COVID-19 syndrome (PCS), is a relatively new condition, its incidence is still unclear and differs between studies. In this cohort study, we aimed to estimate the incidence of PCS and to identify its risk factors in the Tunisian population. This is a prospective cohort study that enrolled patients diagnosed with COVID-19 from the triage unit of the University Hospital of Monastir, Tunisia. between April 2021 and June 2022. Patients were contacted by phone for a follow-up evaluation of PCS 12- weeks after the diagnosis date. A total of 1451 individuals diagnosed with COVID-19 during the study period, responded to the follow-up evaluation after 3 months. The incidence of PCS was found to be 44.03% (95% CI [41.47; 46.58]), with fatigue being the most common symptom (21.5%), followed by cognitive impairment (10.3%), including memory loss and difficulty concentrating. Multivariate analysis revealed that the main associated factors to PCS were female gender (RR = 1.54; CI95% [1.30 - 1.82]), pre-existing comorbidities (RR = 1.30; CI95% [1.10 - 1.52]), duration of acute COVID-19 illness (days) (RR = 1.02; CI95% [1.01 - 1.03]), hospitalization (RR = 1.27; CI95% [1.05 - 1.53]), number of COVID-19 episodes (RR = 1.46; CI 95% [1.28 - 1.67]) and patients having receive two or more doses of vaccine prior to COVID-19 infection (RR = 0.82; CI95% [0.70 - 0.96]). Our study allowed to estimate the incidence and identify risk factors of PCS. Recognizing these factors could help to better understand the underlying mechanisms and guide interventions for prevention and management of this condition.

Neuropsychiatric Manifestations and Neuroimaging Changes of Neurologic Wilson Disease–A Cross Sectional Study

Background: Wilson disease is genetic disorder of copper metabolism which causes hepatic &amp; neurologic manifestation mainly. Chelator therapy is usually given as first line treatment in symptomatic wilson disease. Objective:  Objective of our study was to evaluate the neuropsychiatric menufestations of wilson disease. Methods: A Cross sectional study was conducted at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, a tertiary care premier Postgraduate Medical Institution of Bangladesh. Forty five (45) patients of neurologic wilson disease were evaluated at In-patient department of Paediatric Neurology, during the period of January 2015 to December 2020. Diagnosis of Neurologic wilson disease was done, based on the characteristic clinical features of progressive deterioration of scholastic performances, dysarthria and gait disorder along with ophthalmologic findings, biochemical &amp; neuroimaging findings. Results: Total numbers of studied cases were 45. Mean age was 124.65± 20.69 months and male to female ratio was 1.8:1. Most of the patient (83.33%) arrived from poor socio-economic background and rural area (66.67%) of Bangladesh.  Among them 20.0% had history of consanguineous mating parents and 17.78% had another affected sibs. Common presenting features were progressive deterioration of school performance (89.74%), gait disturbance (92.31%),   dysarthria (92.31%) and dystonia (41.03%) of our studied children. Neuropsychiatric manifestations were very common among the affected children. Changes in behavior was present in 62.22% cases, and among them mania were present in 57.77% children. Other common neuropsychiatric manifestations were depression (35.55%), generalized anxiety disorder in 31.11% and loss of memory in 20% cases. Ophthalmological manifestations like KF ring (83.33%) also found in majority of patient. Neuroimaging study showed  basal ganglia hyperintensity in 63.63.% , white matter hyper intense signal changes 18.18% cases and ischemic change in grey matter in 18.18% cases. Conclusion: In our study about two third cases of Neurologic Wilson diseases may present with Neuropsychiatric manifestations in children. Behavior changes were commonest neuropsychiatric manifestations which includes depression, mania, generalized anxiety disorder and loss of memory.In neuroimaging study bilateral basal ganglia hyperintensity were found in about three-fourth cases of our studied children. J Bangladesh Coll Phys Surg 2024; 42: 144-148

A LeViT–EfficientNet-Based Feature Fusion Technique for Alzheimer’s Disease Diagnosis

Alzheimer’s disease (AD) is a progressive neurodegenerative condition. It causes cognitive impairment and memory loss in individuals. Healthcare professionals face challenges in detecting AD in its initial stages. In this study, the author proposed a novel integrated approach, combining LeViT, EfficientNet B7, and Dartbooster XGBoost (DXB) models to detect AD using magnetic resonance imaging (MRI). The proposed model leverages the strength of improved LeViT and EfficientNet B7 models in extracting high-level features capturing complex patterns associated with AD. A feature fusion technique was employed to select crucial features. The author fine-tuned the DXB using the Bayesian optimization hyperband (BOHB) algorithm to predict AD using the extracted features. Two public datasets were used in this study. The proposed model was trained using the Open Access Series of Imaging Studies (OASIS) Alzheimer’s dataset containing 86,390 MRI images. The Alzheimer’s dataset was used to evaluate the generalization capability of the proposed model. The proposed model obtained an average generalization accuracy of 99.8% with limited computational power. The findings highlighted the exceptional performance of the proposed model in predicting the multiple types of AD. The recommended integrated feature extraction approach has supported the proposed model to outperform the state-of-the-art AD detection models. The proposed model can assist healthcare professionals in offering customized treatment for individuals with AD. The effectiveness of the proposed model can be improved by generalizing it to diverse datasets.