Memory Loss Research Articles

Whole exome sequencing identifies risk variants associated with intracranial epidermoid cyst deterioration: A case report

BACKGROUND Intracranial epidermoid cyst (IEC) transformation to malignant squamous cell carcinoma (SCC) is extremely rare, and its etiology is yet unknown. Currently, SCC is treated by performing surgery, followed by a combination of radiotherapy and chemotherapy. It is crucial to identify efficient and trustworthy therapeutic targets for SCC to improve its diagnosis, prognosis, and treatment. CASE SUMMARY In this study, we report the case of a 47-year-old female patient with SCC, which progressed from IEC in the left internal capsule region. The patient was sought treatment at our hospital for severe diplopic vision, accompanied with speech disorder and memory loss. Based on the clinical and postoperative pathology, this patient was finally diagnosed with SCC. To identify disease-causing variants, whole exome sequencing (WES) was performed on the proband. WES revealed two pathogenic missense mutations on Gap junction protein beta 2 (GJB2) (c.257C>T) and Toll-like receptor 2 (TLR2) (c.1039A>G), respectively. CONCLUSION This study provided the first clinical evidence for demonstrating the role of GJB2 and TLR2 in IEC development and treatment. We further confirmed WES as a robust and reliable technique for underlying rare and complex disease-related genetic factor identification.

Proposed Mechanisms of Cell Therapy for Alzheimer’s Disease

Alzheimer’s disease is a progressive neurodegenerative disorder characterized by mitochondria dysfunction, accumulation of beta-amyloid plaques, and hyperphosphorylated tau tangles in the brain leading to memory loss and cognitive deficits. There is currently no cure for this condition, but the potential of stem cells for the therapy of neurodegenerative pathologies is actively being researched. This review discusses preclinical and clinical studies that have used mouse models and human patients to investigate the use of novel types of stem cell treatment approaches. The findings provide valuable insights into the applications of stem cell-based therapies and include the use of neural, glial, mesenchymal, embryonic, and induced pluripotent stem cells. We cover current studies on stem cell replacement therapy where cells can functionally integrate into neural networks, replace damaged neurons, and strengthen impaired synaptic circuits in the brain. We address the paracrine action of stem cells acting via secreted factors to induce neuroregeneration and modify inflammatory responses. We focus on the neuroprotective functions of exosomes as well as their neurogenic and synaptogenic effects. We look into the shuttling of mitochondria through tunneling nanotubes that enables the transfer of healthy mitochondria by restoring the normal functioning of damaged cells, improving their metabolism, and reducing the level of apoptosis.

Valproate Administration to Adult 5xFAD Mice Upregulates Expression of Neprilysin and Improves Olfaction and Memory.

It is well known that the development of neurodegeneration, and especially Alzheimer's disease (AD), is often accompanied by impaired olfaction which precedes memory loss. A neuropeptidase neprilysin (NEP)-a principal amyloid-degrading enzyme in the brain-was also shown to be involved in olfactory signalling. Previously we have demonstrated that 5xFAD mice develop olfactory deficit by the age of 6months which correlated with reduced NEP expression in the brain areas involved in olfactory signalling. The aim of this study was to analyse the effect of administration of a histone deacetylase inhibitor, valproic acid (VA), to adult 5xFAD mice on their olfaction and memory as well as on brain morphology and NEP expression in the parietal cortex (PC) and hippocampus (Hip). The data obtained demonstrated that administration of VA to 7-month-old mice (200mg/kg of body weight) for 28days resulted in improvement of their memory in the Morris water maze as well as olfaction in the odor preference and food search tests. This correlated with increased expression of NEP in the PC and Hip as well as a reduced number of amyloid plaques in these brain areas. This strongly suggests that NEP can be considered an important therapeutic target not only in AD but also in olfactory loss.

Gene-dose-dependent reduction of Fshr expression improves spatial memory deficits in Alzheimer's mice.

High post-menopausal levels of the pituitary gonadotropin follicle-stimulating hormone (FSH) are strongly associated with the onset of Alzheimer's disease (AD). We have shown recently that FSH directly activates the hippocampal FSH receptors (FSHRs) to drive AD-like pathology and memory loss in mice. To unequivocally establish a role for FSH in memory loss, we depleted the Fshr on a 3xTg background and utilized Morris Water Maze to study deficits in spatial memory. 3xTg;Fshr+/+ mice displayed impaired spatial memory at 5 months of age. The loss of memory acquisition and retrieval were both rescued in 3xTg;Fshr-/- mice and, to a lesser extent, in 3xTg;Fshr+/- mice-documenting clear gene-dose-dependent prevention of spatial memory loss. Furthermore, at 5 and 8 months, sham-operated 3xTg;Fshr-/- mice showed better memory performance during the learning and/or retrieval phases, further suggesting that Fshr deletion prevents age-related progression of memory deficits. This prevention was not seen when mice were ovariectomized, except in the 8-month-old 3xTg;Fshr-/- mice. There was also a gene-dose-dependent reduction mainly in the amyloid β40 isoform in whole brain extracts. Finally, serum FSH levels <8 ng/mL in 16-month-old APP/PS1 mice were associated with better retrieval of spatial memory. Collectively, the data provide compelling genetic evidence for a protective effect of inhibiting FSH signaling on the progression of spatial memory deficits in mice and lay a firm foundation for the use of an FSH-blocking agent for the early prevention of memory loss in post-menopausal women.

Comprehensive Approach to Speech and Language Assessment in Recurrent Meningioma: A Case Study

Meningioma is a tumor that arises from the meninges - the membranes that surround the brain and spinal cord. It compresses the adjacent brain tissues, nerves and vessels, leading to changes in vision, loss of smell, headaches, hearing loss or ringing in the ears, memory loss, seizure and most importantly communication difficulty. It affects mainly the elderly above the age of 60, at a female: male ratio of 3:2. Recurrence and progression are well known and are frequent characteristics of meningiomas. The present study aimed to perform a comprehensive approach to speech and language assessment in a case with recurrent meningioma. A case reported following postsurgical recurrent meningioma in the left parietal temporal area, exhibiting symptoms of language, speech and swallowing difficulty associated with a weakness in the left upper and lower limb. The evaluation process from a speech and language perspective involved perceptual and instrumental assessment of cognition, communication and swallowing using tests and tools. The case was found to have comorbid disorders of nonfluent aphasia associated with neuro cognitive deficit, mild dysphagia, mild dementia and dysarthria of speech. Though the presence of language and speech disorders in case of recurrent meningioma is not common, the severity of the disorder may lead to severe communication deficit. Assessing and interpreting an individual's communication ability involves the integration of a variety of information collected in the evaluation process. Keywords: Recurrent meningioma, dysphagia, aphasia, dysarthria

Effect of JM-20 on Age-Related Cognitive Impairment in Mice.

The decline in cognitive function associated with aging significantly impacts the well-being of elderly individuals and their families. This decline is a major recognized risk factor for neurodegenerative diseases, notably Alzheimer's disease. Animal models of aging provide a platform for evaluating drugs concerning aspects like memory and oxidative stress. JM-20 has demonstrated protective effects on short-term memory acquisition and consolidation, along with antioxidant properties and modulation of Acetylcholinesterase activity. This study assesses the potential protective JM-20 against cognitive decline and age-related memory loss. For the study, aged mice exhibiting aging-associated damage were initially selected. Experimental groups were then formed, and the effect of 8mg/kg of JM-20 was evaluated for 40 days on aging-related behavior, such as spatial memory, novelty recognition memory, ambulatory activity, and anxiety. Subsequently, animals were sacrificed, and the hippocampal region was extracted for redox studies and to assess acetylcholinesterase activity. Results indicated that JM-20 at 8mg/kg reversed damage to spatial working and reference memory, exhibiting performance comparable to untreated young adult animals. Furthermore, JM-20 preserved the enzymatic activity of superoxide dismutase, catalase, and total sulfhydryl levels in age-related cognitive impairment in mice, indicating a potent protective effect against oxidative events at the brain level. However, only young, healthy animals showed decreased acetylcholinesterase enzyme activity. These findings provide preclinical pharmacological evidence supporting the neuroprotective activity of JM-20, positioning it as a promising therapeutic candidate for treating memory disorders associated with aging.

Symptom profile, case and symptom clustering, clinical and demographic characteristics of a multicentre cohort of 1297 patients evaluated for Long-COVID.

Long-COVID symptoms remain incompletely defined due to a large heterogeneity in the populations studied, case definitions, and settings of care. The aim of this study was to assess, in patients accessing care for Long-COVID, the profile of symptoms reported, the possible clustering of symptoms and cases, the functional status compared to pre-infection, and the impact on working activity. Multicentre cohort study with a collection of both retrospective and prospective data. Demographics, comorbidities, severity and timing of acute COVID, subjective functional status, working activity and presence of 30 different symptoms were collected using a shortened version of the WHO Post COVID-19 Case Report Form. The impact on working activity was assessed in multivariable logistic regression models. Clustering of symptoms was analysed by hierarchical clustering and the clustering of cases by two-step automatic clustering. The study evaluated 1297 individuals (51.5% women) from 30 clinical centres. Men and women had different profiles in terms of comorbidities, vaccination status, severity and timing of acute SARS-CoV-2 infection. Fatigue (55.9%) and dyspnea (47.2%) were the most frequent symptoms. Women reported more symptoms (3.6 vs. 3.1, p < 0.001), with a significantly higher prevalence of memory loss, difficult concentration, cough, palpitation or tachycardia, dermatological abnormalities, brain fog, headache and visual disturbances. Dyspnea was more common in men. In the cluster analysis of the 19 more common symptoms, five aggregations were found: four two-symptom clusters (smell and taste reduction; anxiety and depressed mood; joint pain or swelling and muscle pain; difficult concentration and memory loss) and one six-symptom cluster (brain fog, equilibrium/gait disturbances, headache, paresthesia, thoracic pain, and palpitations/tachycardia). In a multivariable analysis, headache, dyspnea, difficult concentration, disturbances of equilibrium or gait, visual disturbances and muscular pain were associated with reduced or interrupted working activity. Clustering of cases defined two clusters, with distinct characteristics in terms of phase and severity of acute infection, age, sex, number of comorbidities and symptom profile. The findings provide further evidence that Long-COVID is a heterogeneous disease with manifestations that differ by sex, phase of the pandemic and severity of acute disease, and support the possibility that multiple pathways lead to different clinical manifestations.

Palmitoyl-L-carnitine induces tau phosphorylation and mitochondrial dysfunction in neuronal cells.

Alzheimer's disease (AD) is characterized by cognitive decline and memory loss, involving mechanisms such as tau hyperphosphorylation and mitochondrial dysfunction. Increasing evidence suggests that age-related alterations in metabolite levels are crucial for the pathogenesis of AD. Here, we analyzed serum metabolites from mice of various ages (2, 4, 14, and 21 months old) using mass spectrometry. We identified palmitoyl-L-carnitine as a key metabolite with significantly increased levels in aged mice. In vitro experiments with SH-SY5Y neuronal cells demonstrated that palmitoyl-L-carnitine treatment enhanced tau phosphorylation, increased mitochondrial fission, and elevated intracellular calcium levels. Furthermore, the increased levels of tau phosphorylation were significantly reduced by the inhibition of GSK-3β, CDK5, and calpain, indicating that tau kinases activated by calcium overload are directly involved in the increase of tau phosphorylation. Considering that mitochondrial fission is related to mitochondrial dysfunction, we propose that the elevated level of serum palmitoyl-L-carnitine during aging contributes to AD pathology through these pathways. These findings highlight the significant role of lipid metabolism in neurodegeneration and offer potential therapeutic targets for age-related diseases, including AD.

Anxiety, memory, and social impairments in the YAC128 mouse model of Huntington’s disease

Background Huntington’s disease (HD) is an autosomal dominant hereditary disorder, caused by an expansion of polyglutamine in the huntingtin protein. HD is characterized by a progressive decline in motor functions. This decline includes involuntary movements (chorea) and the worsening of controlled motions caused mainly by neuronal dysfunction in the striatum. In addition to the deterioration of motor symptoms, HD patients also suffer from cognitive changes, mood swings, apathy, depression, outbursts of anger, psychosis, and social withdrawal. Objective A comprehensive examination of cognitive, affective, and social changes in the HD mouse model is required for the development of combined therapy for both motor and non-motor deficits in HD. Methods The behavioral tests for anxiety, memory, and social traits were used in this study. Results YAC128 HD transgenic mice exhibited anxiolytic behavior in the novel brightly illuminated environment of the open field and light-dark place preference tests. Moreover, YAC128 HD mice also suffered from a decline in their recognition memory during the novel object recognition test. YAC128 HD mice demonstrated reduced exploration interest during the open field with a non-social target as well as during the first day of the three-chamber social test. Social interaction was also impaired in YAC128 HD mice as it was shown in the social interaction with resident intruder test. Conclusions YAC128 HD mouse model may be used as a model system to test the possible treatments for both motor and non-motor symptoms including memory loss, agitation and social withdrawal.

Multifunctional, fluorene-based modulator of cholinergic and GABAergic neurotransmission as a novel drug candidate for palliative treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory loss and behavioral and psychological symptoms of dementia (BPSD). Given that cholinergic neurons are predominantly affected in AD, current treatments primarily aim to enhance cholinergic neurotransmission. However, imbalances in other neurotransmitters, such as γ-aminobutyric acid (GABA), also contribute to AD symptomatology. In the presented research, by using a combination of crystallography and computational methods we developed 6 as a dual modulator of GABAergic and cholinergic neurotransmission systems. Compound 6 demonstrated inhibition of BuChE (IC50 = 0.21 μM) and GABA transporter 1 (IC50 = 10.96 μM) and 3 (IC50 = 7.76 μM), along with a favorable drug-likeness profile. Subsequent in vivo studies revealed effectiveness of 6 in enhancing memory retention and alleviating anxiety and depression symptoms in animal models, while also proving safe and bioavailable for oral administration. The innovative multi-target-directed ligand 6 offers a new approach to treating cognitive deficits and BPSD in AD.

NIMG-31. CASE REPORT: DIAGNOSIS OF AN INFILTRATIVE GLIOMA IN A LI-FRAUMENI SYNDROME PATIENT OBSCURED BY LESION RESPONSIVENESS TO NSCLC TREATMENT

Abstract Li-Fraumeni syndrome is a rare, autosomal dominant disorder linked to germline mutations of the TP53 suppressor gene. Patients with this syndrome are predisposed to various malignancies and a variety of brain tumors to include choroid plexus carcinoma, medulloblastoma, and glioma. We present a 46-year-old woman with a history of Li-Fraumeni syndrome which manifested with multiple systemic malignancies including breast cancer, ovarian teratoma, and leiomyosarcoma. The patient had been undergoing MRI brain surveillance since 2018, which was initially notable for a right cerebellar midline focus of enhancement associated with slowly evolving right middle cerebellar peduncle FLAIR signal, with no detectable neurologic symptoms. She underwent systemic therapy for non-small cell lung cancer (NSCLC) with pemetrexed/cisplatin. Her next MRI brain in August 2023 showed resolution of the cerebellar enhancement with small residual FLAIR signal. In April 2024, the patient presented with new neurologic symptoms to include ataxia, dizziness, difficulty swallowing, and memory loss. Repeat MRI brain revealed new infiltrative FLAIR signal throughout the right temporal lobe extending from the posterior fossa, contiguous with the previously seen cerebellar findings and consistent with infiltrative glioma. Due to fragmented records and care in multiple systems, her updated MRI initially created a diagnostic challenge with a radiographic interpretation of likely encephalitis. This is a unique case documenting a middle-aged female with Li-Fraumeni syndrome, followed for multiple cancers, presenting with new neurologic symptoms and progressive infiltrative FLAIR changes spanning from the cerebellum into the right temporal lobe. These findings highlight the natural history of a TP53 deficient tumor that ostensibly responded to a cisplatin-based regimen given for a different indication, thereby delaying time to symptom onset and need for biopsy. Surveillance of low grade lesions in patients with underlying tumor predisposition syndromes must be interpreted in context of systemic disease burden and concurrent treatments for other neoplasms.

Caffeic Acid Attenuates Neuronal Apoptosis, Oxidative Stress, and Memory Deficits via Antioxidant Properties in Aging Rats Induced by D-Galactose.

Aging is a main factor related to cognitive deficits. D-Galactose (D-gal), a monosaccharide, increases oxidative stress leading to cellular senescence, memory deficits, and neuronal apoptosis. Caffeic acid (CA) is an antioxidant that can interrupt free radicals and reduce oxidative stress. The present study purposely evaluated the benefits of CA in attenuating loss of neuronal apoptosis, oxidative stress, and memory in D-gal-activated rat brain aging. Male Sprague-Dawley rats were arbitrarily allocated into 6 groups (9 rats per group). The D-gal group was intraperitoneal (i.p.) injected with D-gal (50mg/kg). The CA groups were orally given 20 or 40mg/kg CA for 8weeks. During that time, the co-treatment groups were given 50mg/kg of D-gal and 20 or 40mg/kg of CA. The results reveal that animals receiving only D-gal showed memory deficit in both the novel object location (NOL) and novel object recognition (NOR) tests. Reduction in scavenging enzyme activities and levels of B-cell lymphoma 2 (Bcl-2) protein expression were detected in the D-gal group. Furthermore, D-gal treatment significantly enhanced in the number of p21 positive cells in the subgranular zone (SGZ) of the hippocampal dentate gyrus, Bcl-2 associated X protein (Bax) and caspase3 protein expression, and malondialdehyde (MDA) levels. By contrast, both 20 and 40mg/kg CA treatment alleviated these effects. These consequences confirmed that D-gal-activated brain aging led to enhancing apoptotic protein expression including Bcl-2, Bax, and caspase3 and memory impairments. Nevertheless, CA attenuated these effects in brain aging induced by D-gal via antioxidant properties.

Inhibitory Potency of Chlorogenic Acid from Apple Cider Vinegar Against Alzheimer’s Disease: Molecular Docking and Dynamics Validation

Objective The primary cause of memory loss is Alzheimer’s disease (AD). Recent studies have shown that natural compounds like apple cider vinegar (ACV) have anti-Alzheimer’s capabilities. Essential components of ACV, such as gallic acid and chlorogenic acid, may be in charge of the drug’s pharmacological effects. Methods Using molecular docking and dynamics (MD), the current work looks at the aspect of ACV that protects against AD. To study the conformational relationships and interaction mechanisms between two biological molecules (such as interactions between proteins and drugs or between proteins), MD simulation is frequently used. MD can help understand molecular structural differences between proteins and small compounds. We used acetylcholinesterase (AChE, PDB ID: 1UT6) to MD chlorogenic and gallic acids, as well as the currently prescribed medication rivastigmine (Standard medication). Furthermore, we determine the binding affinity, which may be responsible for AChE inhibition. MD simulations were performed on docked complexes of chlorogenic acid, gallic acid, and rivastigmine with receptor 1UT6 for a 300 ns trajectory to ensure the stability of docked ligand-protein complexes. Results The results showed that chlorogenic acid has the highest binding affinity and stability for AChE inhibition. In the docking and dynamics analysis, both techniques have predicted chlorogenic acid to be a potential constituent of ACV which shows a similar activity when compared to rivastigmine by virtue of binding affinity. Conclusion These findings identify chlorogenic acid as the key component of ACV that protects against AD-related cognitive and behavioral impairments. This finding will be critical in the development of ACV-based drugs for Alzheimer’s disease treatment.

The expression of shelterin genes and telomere repeat analysis and their effect on Alzheimer's disease.

Alzheimer's disease (AD) is an age-related dementia disorder characterized by memory loss and behavioral changes. Maintaining the integrity of telomere shortening in AD is important for cellular survival and homeostasis in all cells, especially glial cells. The shelterin protein complex provides telomere integrity. Measuring the expression levels of shelterin genes and determining the telomere lengths regulated by this complex will reveal their effects on AD progression and adult neurogenesis and will allow the detection of the disease or the determination of the progression process from an accessible tissue. The study population included 111 patients and 91 healthy controls (male and female, < 50 age). The clinical histories (age, gender, hypertension, diabetes mellitus, obesity, cardiovascular disease, MMSE, medication use, family history, sleep disorders, seizure), covariates (HGB, ESR, Na, P, Cl, BUN, CRP, B12, TSH, Glucose, and MRI findings) and the expressional changes of shelterin genes (TERF1, TERF2, TINF2, POT1, TPP1, and RAP1) between the patient and control groups were evaluated relatively. ROC analyses determined the diagnostic power of telomere repeats and gene expressions. In conclusion, upregulation of expression of shleterin complex genes was detected in AD, where telomeres are significantly shorter than in controls (P < 0.05). However, only TERF2 and RAP1 were significant (P < 0.05). A positive relationship was detected between telomere repeats and these genes (P < 0.05). Telomere repeats may be a strong diagnostic criterion to distinguish AD individuals from healthy individuals (AUC = 1.000). The upregulation of TERF2 and RAP1 core genes required for telomere integrity results in the instability of excessively shortened telomeres. Expression silencing of these genes may increase telomerase activity and maintain cellular survival. Also, the detection of telomere repeats has potential in the early diagnosis of AD patients.

Novel Piperazine Based Compounds Target Alzheimer's Disease Relevant Amyloid β42 and Tau Derived Peptide AcPHF6, and the Lead Molecule Increases Viability in the Flies Expressing Human Tau Protein.

Alzheimer's disease (AD) is the leading form of dementia in the United States and the world. The pathophysiology of AD is complex and multifaceted. Accumulation of senile plaques and neurofibrillary tangles (NFTs) are hallmarks of AD. The aggregation of amyloid β (senile plaques) and tau tangles (NFTs) results in the death of neurons in the cortex and hippocampus, which manifests itself in cognitive decline and memory loss. Current therapies rely on conventional approaches that have only treated the underlying symptoms without disease modification. Data from clinical studies point to a complex role of amyloid β (Aβ) in a way that enhances the tau phenotype throughout the disease process. To address the co-pathogenic role of Aβ and tau, we undertook development of multitarget compounds aiming at both tau and Aβ to slow or stop disease progression and provide neuroprotection. Here, we demonstrate a dose-dependent effect of the novel test compounds that inhibit aggregation of AcPHF6 (a shorter version of tau protein) and Aβ1-42 peptides in thioflavin T fluorescent assays. The compounds were also shown to disaggregate preformed aggregates dose dependently. To further validate these findings, circular dichroism experiments were carried out to examine the nature of inhibition. Additionally, transmission electron microscopy experiments were carried out to gain insights into the morphologies of aggregates obtained from dose-dependent inhibition of AcPHF6 and Aβ1-42 as well as dissociation of preformed aggregates from these peptides. Compounds D-687 and D-688 reversed Aβ1-42 induced toxicity in SH-SH5Y cells, significantly demonstrating neuroprotective properties. Finally, in a study with Drosophila melanogaster expressing human tau protein isoform (2N4R) in all the neurons, compound D-688 significantly increased the survival of flies compared to vehicle treated controls. Future studies will further examine the neuroprotective properties of these lead compounds in various animal models.

Unveiling tomorrow: Carbonic anhydrase activators and inhibitors pioneering new frontiers in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder and a principal basis of dementia in the elderly population globally. Recently, human carbonic anhydrases (hCAs, EC 4.2.1.1) were demonstrated as possible new targets for treating AD. hCAs are vital for maintaining pH balance and performing other physiological processes as they catalyze the reversible hydration of carbon dioxide to bicarbonate and a proton. Current research indicates that hCA plays a role in brain functions critical for transmitting neural signals. Activation of carbonic anhydrase (CA) has emerged as a promising avenue in addressing memory loss and cognitive issues. Conversely, the exploration of CA inhibition represents a novel frontier in this field. By enhancing glial fitness and cerebrovascular health and blocking amyloid-β (Aβ)-induced mitochondrial dysfunction pathways, cytochrome C (CytC) release, caspase 9 activation, and H2O2 generation in neurons, CA inhibitors improve cognition and lessen the pathology caused by Aβ. Recent research has pushed hCAs into the spotlight as critical players in AD pathogenesis and precise therapeutic targets. The captivating dilemma of choosing between hCA inhibitors and activators looms large, as inhibitors reduce Aβ aggregation and improve cerebral blood flow, while activators enhance cerebrovascular functions and restore pH balance. The current review sheds light on the clinical evidence for hCAs and the roles of inhibitors and activators in AD. Additionally, this review offers a fascinating outlook on the data that may aid medicinal chemists in designing and developing new leads that are more effective and selective for upcoming in vitro and in vivo studies, allowing for the discovery and introduction of novel drug candidates for the treatment of AD to the market and into the clinical pipeline.

Acute depletion of complement C3 with cobra venom factor attenuates memory deficits induced by status epilepticus.

Status epilepticus (SE) significantly increases the risk for the development of unprovoked seizures, memory loss, and temporal lobe epilepsy. Our prior studies showed that SE increases complement C3 signaling in the hippocampus, which parallels memory deficits. Additionally, C3 knockout (KO) mice were protected against SE-induced memory impairments, suggesting a mechanistic role for C3 in this pathophysiology. In this study, we utilized cobra venom factor (CVF), a structural analog of C3 that results in its depletion, to investigate the protective effects of post-SE C3 ablation on memory deficits that develop during epileptogenesis. SE was induced in male rats using the chemoconvulsant pilocarpine. Two weeks later, control (C) and SE rats were treated with either vehicle (V) or CVF. Recognition memory was assessed using the novel object recognition (NOR) test in four groups (C + V, C + CVF, SE + V, and SE + CVF). Immunoblotting was used to measure hippocampal protein levels of C3 along with synaptic, astrocyte, and blood-brain barrier (BBB) stability markers, Psd95, GFAP, and albumin, respectively. In the NOR test, rats in the C + V and C + CVF groups spent more time exploring the novel object. SE + V rats explored both objects equally, while SE + CVF rats spent significantly more on the novel object, suggesting a rescue of cognitive performance by CVF. While CVF-mediated C3 depletion did not restore normal protein levels of Psd95 or GFAP in hippocampi of SE + CVF rats, CVF treatment attenuated SE-induced extravasation of albumin, suggesting potential rescue of BBB stability. Our findings indicate that acute C3 depletion with CVF can attenuate memory deficits that develop during SE-induced epileptogenesis. This finding further suggests that targeting C3 could hold promise in addressing cognitive comorbidities associated with SE and acquired epilepsy. A long-lasting seizure, known as status epilepticus (SE), can raise the chance of having more seizures in the future and can lead to memory problems. While the exact reasons for these issues are not completely known, it is believed that brain inflammation might be involved. In this study, we show that the activation of the body's immune response, especially a part called the C3 component, plays a role in the memory problems that occur after an episode of SE.

Human herpesvirus 6 (HHV-6) encephalitis secondary to chimeric antigen receptor (CAR)-T cell therapy.

Human herpesvirus (HHV)-6 encephalitis secondary to chimeric antigen receptor (CAR)-T cell therapyis relatively rare in clinical practice and needs to be differentiated from immune effector cell-associatedneurotoxicity syndrome (ICANS). We retrospectively reported a case of HHV-6 encephalitis secondary to CAR-T cell therapy. A male patient from China with diffuse large B-cell lymphoma underwent chimeric CAR-T cell therapy anddeveloped a generalized rash on the 8th day, followed by cognitive changes, memory loss, and disorientation onthe 14th day after CAR-T cell therapy. Initially, ICANS was suspected. A lumbar puncture was performed on the 18th day. The cerebrospinal fluid (CSF) analysis revealed slightly elevated protein levels and a high presence of HHV-6B sequences by mNGS. Brain MRI showed bilateral hippocampal abnormalities. The patient was ultimatelydiagnosed with HHV-6 encephalitis and treated with ganciclovir and dexamethasone. After one week of treatment,follow-up CSF analysis showed a reduction in HHV-6B sequences. The patient was discharged with improvedmemory and orientation. HHV-6 encephalitis secondary to CAR-T cell therapy may be easily confused with ICANS. Timely andaggressive diagnostic procedures, such as mNGS of CSF and cranial imaging, along with prompt antiviral therapy,are crucial for improving patient outcomes.

Explainable AI for Alzheimer Detection: A Review of Current Methods and Applications

Alzheimer’s disease (AD) is the most common cause of dementia, marked by cognitive decline and memory loss. Recently, machine learning and deep learning techniques have introduced promising solutions for improving AD detection through MRI, especially in settings where specialists may not be readily available. These techniques offer the potential to assist general practitioners and non-specialists in busy clinical environments. However, the ‘black box’ nature of many AI techniques makes it challenging for non-expert physicians to fully trust their diagnostic accuracy. In this review, we critically evaluate current explainable AI (XAI) methods applied to AD detection and highlight their limitations. In addition, a new interpretability framework, called “Feature-Augmented”, was theoretically designed to improve model interpretability. This approach remains underexplored, primarily due to the scarcity of explainable AD-specific datasets. Furthermore, we underscore the importance of AI models being accurate and explainable, which enhance diagnostic confidence and patient care outcomes.

Implementing palliative and end of life care for people with dementia.

Dementia is characterised by memory loss, behavioural changes and decline of cognitive, social and physical functions and is a life-limiting condition. At the point of diagnosis it is classed as a palliative condition, yet there is limited public and healthcare professional awareness that, once diagnosed, a person will either die of dementia or die with dementia. This article discusses how the recognition and timing of the need for palliative dementia care is pivotal in providing person-centred care. The authors explore factors such as optimal prognostication, advance care planning, staff education and accessing support from palliative and end of life care teams and Admiral Nurses. The authors also use a fictional case study to demonstrate best practice in palliative dementia care.