Memory Disorders Research Articles

Astrocytes and Memory: Implications for the Treatment of Memory-related Disorders.

Memory refers to the imprint accumulated in the brain by life experiences and represents the basis for humans to engage in advanced psychological activities such as thinking and imagination. Previously, research activities focused on memory have always targeted neurons. However, in addition to neurons, astrocytes are also involved in the encoding, consolidation, and extinction of memory. In particular, astrocytes are known to affect the recruitment and function of neurons at the level of local synapses and brain networks. Moreover, the involvement of astrocytes in memory and memory-related disorders, especially in Alzheimer's disease (AD) and post-traumatic stress disorder (PTSD), has been investigated extensively. In this review, we describe the unique contributions of astrocytes to synaptic plasticity and neuronal networks and discuss the role of astrocytes in different types of memory processing. In addition, we also explore the roles of astrocytes in the pathogenesis of memory-related disorders, such as AD, brain aging, PTSD and addiction, thus suggesting that targeting astrocytes may represent a potential strategy to treat memory-related neurological diseases. In conclusion, this review emphasizes that thinking from the perspective of astrocytes will provide new ideas for the diagnosis and therapy of memory-related neurological disorders.

Clinical and Demographic Profile of Syrian Patients with Malignant Glioma: A Six-Month Retrospective Analysis

This study presents a retrospective analysis of glioblastoma cases admitted to Tishreen University Hospital in Lattakia, Syria, between February and August 2024. The study examines the several potential risk factors including age, sex, genetic predispositions, and lifestyle factors such as smoking and alcohol consumption. It also explores the most commonly encountered tumor grade and the presence of various neurological symptoms, as well as treatment outcomes. A total of 30 glioblastoma were enrolled in this study, 63% of which were males, and the highest age incidence was between 40 and 50 years. Only 6% had a family history of glioblastoma, and 66% of the patients were smokers. Memory disorders, visual impairments, and headaches were common symptoms, with 100% of the patients reporting nausea and vomiting. Glioblastoma diagnosis was primarily established through MRI with contrast (76%), and the predominant treatment modality was surgery combined with radiotherapy and chemotherapy (80%). Post-treatment relapse occurred in 26% of the patients, with a median remission period of four months. These findings provide important insights into the clinical characteristics and treatment outcomes of glioblastoma patients in this region.

High Behavioral Reactivity to Novelty as a Susceptibility Factor for Memory and Anxiety Disorders in Streptozotocin-Induced Neuroinflammation as a Rat Model of Alzheimer’s Disease

Individual differences in responsiveness to environmental factors, including stress reactivity and anxiety levels, which differ between high (HR) and low (LR) responders to novelty, might be risk factors for development of memory and anxiety disorders in sporadic Alzheimer’s disease (sAD). In the present study, we investigated whether behavioral characteristics of the HR and LR rats, influence the progression of sAD (neuroinflammation, β-amyloid peptide, behavioral activity related to memory (Morris water maze) and anxiety (elevated plus maze, white and illuminated open field test) in streptozotocin (STZ)-induced neuroinflammation as a model of early pathophysiological alterations in sAD. Early (45 days) in disease progression, there was a more severe impairment of reference memory and higher levels of anxiety in HRs compared with LRs. Behavioral depression in HRs was associated with higher expression of β-amyloid deposits, particularly in the NAcS, and activation of microglia (CD68+ cells) in the hypothalamus, as opposed to less inflammation in the hippocampus, particularly in CA1, compared with LRs in late (90 days) sAD progression. Our findings suggest that rats with higher behavioral activity and increased responsivity to stressors show more rapid progression of disease and anxiety disorders compared with low responders to novelty in the STZ-induced sAD model.

Memory impairment after one year of the acute episode of Covid-19 infection

Abstract Introduction Memory impairment is one of the most frequently reported sequelae of COVID-19 infection. The aim of our study was to estimate the risk of memory disorders one year after the acute episode of COVID-19 infection in the Tunisian population of Monastir. Methods This is a cohort study conducted in Monastir University Hospital. The study included two groups: Exposed subjects were randomly selected among those with a positive diagnosis of COVID-19 between September 2021 and January 2022. The non exposed group was selectd among subjects with a negative COVID-19 diagnosis during the same period and who had no COVID infection during the following year. The Mac Nair scale was used to assess memory impairment after one year of follow up. Results Our study included 140 subjects diagnosed with Covid-19 and 139 subjects who had never been in contact with this virus. The incidence rate of memory impairment at one year post-Covid-19 infection was 17.9% (IC95% [11.5 - 24.2%]), whereas in the non exposed group it was 9.4% (IC95% [4.45% -14.5%]). Multivariate analysis revealed that the group exposed to Covid-19 had a significantly higher Mac-Nair Total score after one year of the acute episode of infection compared with the non exposed group (exp β = 1.25, IC95% [1.10; 1.42]). The other main predictors of memory impairment in the study population were age (exp β = 1.006, IC95% [1.001; 1.01]), diabetes (exp β = 1.67, IC95% [1.44; 1.95]), history of anxiety and depression ((exp β = 1.71, IC95% [1.35; 2.17]) and obesity (exp β = 1.25, IC95% [1.10; 1.42]), whereas vaccination with two or more doses prior to COVID-19 infection (exp β = 0.84, IC95% [0.74; 0.96]) and male gender (exp β = 0.65, IC95% [ 0.57; 0.73]) were found to be protective against these disorders. Conclusions Our study allowed us to estimate the risk of long-term memory disorders following Covid-19 infection. This could help better guide preventive measures to reduce the incidence of these disorders. Key messages • The incidence rate of memory impairment at one year post-Covid-19 infection was 17.9%. • The main other predictors of memory impairment were age, female gender, diabetes, history of anxiety and depression and obesity whereas vaccination prior to COVID-19 infection was a protective factor.

The Digitized Memory Clinic.

Several major challenges, including an ageing population and declining workforce and the implementation of recent breakthrough therapies for Alzheimer disease, are prompting a necessary rethink of how people with neurodegenerative dementias are diagnosed and medically managed. Digital health technologies could play a pivotal part in this transformation, with new advances enabling the collection of millions of data points from a single individual. Possible applications include unobtrusive monitoring that aids early detection of disease and artificial intelligence-based health advice. To translate these advances to meaningful benefits for people living with a disease, technologies must be implemented within a system that retains the physician expert as a central figure in decision-making. This Perspective presents a new framework, termed the Digitized Memory Clinic, for the diagnostic pathway of neurodegenerative dementias that incorporates digital health technologies with currently available assessment tools, such as fluid and imaging biomarkers, in an interplay with the physician. The Digitized Memory Clinic will manage people across the entire disease spectrum, from the detection of risk factors for cognitive decline and the earliest symptoms to dementia, and will replace the present paradigm of a pure 'brick-and-mortar' memory clinic. Important ethical, legal and societal barriers associated with the implementation of digital health technologies in memory clinics need to be addressed. The envisioned Digitized Memory Clinic aims to improve diagnostics and enable precise disease-tracking prognostication for individuals with memory disorders and to open new possibilities, such as precision medicine for prevention and treatment.

Alzheimer's disease and other memory disorders in the age of AI: reflection and perspectives on the 120th anniversary of the birth of Dr. John von Neumann.

Two themes are coming to the forefront in this decade: Cognitive impairment of an aging population and the quantum leap in developing artificial intelligence (AI). Both can be described as growing exponentially and presenting serious challenges. Although many questions have been addressed about the dangers of AI, we want to go beyond the fearful aspects of this topic and focus on the possible contribution of AI to solve the problem of chronic disorders of the elderly leading to cognitive impairment, like Alzheimer's disease, Parkinson's disease, and Lewy body dementia. Our second goal is to look at the ways in which modern neuroscience can influence the future design of computers and the development of AI. We wish to honor the memory of Dr. John von Neumann, who came up with many breakthrough details of the first electronic computer. Remarkably, Dr. von Neumann dedicated his last book to the comparison of the human brain and the computer as it stood in those years of the mid-1950s. We will point out how his ideas are more relevant than ever in the age of supercomputers, AI and brain implants.

Low Cardiac Output And Brain Function In The Prognosis Of Adult Patients With Heart Failure

Objective: Synthesize the best evidence from the literature describing the relationship between low expenditure and brain function in the prognosis of adult patients with heart failure. Methods: Descriptive integrative review, which performed a search in limited databases from 2009 to 2019, using MeSH and DeCS terms, such as Heart Failure, cardiac output, cognitive dysfunction, memory disorders in the analysis of 20 articles found. Results: It was identified that there is evidence that patients with heart failure suffer from prevalent mental disorders associated with numerous processes, including attention and learning deficits, decreased psychomotor speed, memory dysfunction, difficulties in solving problems and decreased executive function which worsens the prognosis because it is associated with poor adherence to treatment and lower quality of life Conclusion: In heart failure, cognitive resources decrease and cognitive demands increase, therefore, nursing must establish strategies for promotion and prevention, timely detection that comprehensively address the patient, aiming to improve self-care, in order to control medication, therapeutic regimens. and dietary, to ensure adherence to treatment and thus improve the quality of life of the patient and his family.

Memory-enhancing activity of verapamil in murine models of stress

Purpose: To evaluate the benefit of verapamil on stress-induced memory impairment in mice. Methods: Forty-eight (48) mice were used in this study. They were divided into two equal groups based on the two models of stress used in this study (sleep deprivation and hypoxia). Each model was further divided into 4 groups of six animals each. The mice in the sleep deprivation model were suspended on a platform above water while in the hypoxic model, mice were locked in an airless container for 20 min daily throughout the experiment. As for the intervention, 25 and 50 mg/kg verapamil were preadministered via the oral route to study groups, except the normal control group and negative control group in both models. After seven-day stress and intervention, the mice were subjected to behavioural tests (Y-maze and object recognition tests), biochemical assays (for acetylcholinesterase activity) and histochemical analysis. Results: Stress caused a significant (p < 0.05) impairment in the consolidation and retrieval of working and recognition memories. Also, acetylcholinesterase activity was significantly (p < 0.05) enhanced in the stressed groups when compared to control groups. Similarly, the histological analysis revealed a significant decline in population (p < 0.05), distribution and density of viable neurons in specific areas of the hippocampus and prefrontal cortex. These alterations were significantly (p < 0.05) attenuated in verapamil-treated groups almost in a dose-dependent pattern. Conclusion: Verapamil displays significant memory-enhancing effects in two (2) murine models of stress. Antihypertensives should therefore be considered a viable prospect in the management of stress-related memory disorders after additional studies have been done to establish the mechanisms of action.

Exploring the septum pellucidum: Short review of anatomical insights and the clinical impact of septum pellucidum and cavum septi pellucidi

BackgroundThe septum pellucidum (SP) is a thin, triangular, and delicate structure in the brain. It consists of two layers of white and gray matter and topographically is located between the lateral ventricles. The SP is part of the limbic system, which involves emotions, behavior, and memory. AimThis concise review provides an overview of the anatomy, development, and clinical significance of the SP, with a specific focus on cavum septi pellucidi (CSP). It also discusses its implications for brain function and its potential link to neurological disorders. ConclusionsAs an essential structure within the limbic system, the SP and its associated variations, like CSP, offer valuable insights into brain development and function, particularly concerning emotions, memory, and psychiatric disorders. Understanding the role of the septum pellucidum and its developmental anomalies may shed light on various neuropsychiatric conditions and help guide future research and clinical practices.

Proinflammatory factors inhibition and fish oil treatment: A promising therapy for neonatal seizures

Brain injury is one of the most important causes of infant mortality and chronic neurological disabilities. Hypoxia is an acute brain injury which led to various cognitive, behavioral, and memory disorders throughout life. Previous studies reported neuroprotective possibilities for fish oil (FO) in brain-injured situations. In this study, we evaluated the effect of the FO diet during the lactation period on seizure activity, behavioral performance, histomorphometry, and inflammatory changes in the brains of hypoxia rats. Male Wistar rats were randomly divided in to 4 groups: Sham (intact rats), hypoxia, FO and FO+hypoxia groups. Hypoxia was induced by keeping neonate rats at PND12 in a hypoxic chamber (7 % oxygen and 93 % nitrogen intensity) for 15 minutes. In the FO groups, rats received oral FO (1 ml/day) for 12 days during the lactation period. Seizure activity was assessed by measuring the number of tonic-clonic seizures and seizure thresholds. Novel object recognition tests (NORT), rotarod, and open field tests were used to measure behavioral performances. A Histological study was performed to evaluate histomorphometric changes in the hippocampus and cerebellum. The gene expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was measured using RT-PCR. Findings showed that the number of tonic-clonic seizures, atrophy, and cell death in the hippocampus and cerebellum, the gene expression of TNF-α and IL-1β in the hippocampus, and behavioral disorders were significantly increased in the hypoxia rats compared to the sham group. Administration of FO in the hypoxia groups significantly decreased the gene expression of TNF-α and IL-1β, the number of tonic-clonic seizures, and neuronal cell death in the hippocampus and cerebellum compared to the hypoxia groups. Furthermore, it can improve behavioral tasks and cognitions.

Ameliorating Effect of S-Allyl Cysteine (Black Garlic) on 6-OHDA Mediated Neurotoxicity in SH-SY5Y Cell Line

Therapeutic approaches based on isolated compounds derived from natural products are more common in preventing diseases involving inflammation and oxidative stress at present. S-allyl cysteine (SAC) is a promising garlic-derived organosulfur compound with many positive effects in cell models and living systems. SAC has biological activity in various fields, enclosing healing in learning and memory disorders, neurotrophic effects, and antioxidant activity. In this study, we purposed to identify the neuroprotective activity of SAC toward 6-OHDA-induced cell demise in the SH-SY5Ycell line. For this purpose, 6-OHDA-induced cytotoxicity, and biochemical, and gene expression changes were evaluated in SH-SY5Y cells. SH-SY5Y cells grown in cell culture were treated with SAC 24hours before and after 6-OHDA application. Then, cell viability, antioxidant parameters, and gene expressions were measured. Finally, immunofluorescence staining analysis was performed. Our results showed that SAC increased cell viability by 144% at 80µg/mL with pre-incubation (2hours). It was observed that antioxidant levels were significantly increased and oxidative stress marker levels were decreased in cells exposed to 6-OHDA after pre-treatment with SAC (p<0.05). SAC supplementation also suppressed the increase in pro-inflammation levels (TNF-α/IL1/IL8) caused by 6-OHDA (p < 0.05). While 8-OHdG and Nop10 expressions were observed at a mild level in SAC pretreatment depending on the dose, 8-OHdG, and Nop10 expressions were observed at a moderate level in SAC treatment after 6-OHDA application (p<0.05). Our findings demonstrate the positive effect of pretreatment with SAC on SH-SY5Y cells injured by 6-OHDA, suggesting that SAC may be beneficial for neuroprotection in regulating oxidative stress and neuronal survival in an in vitro model of Parkinson's disease.

Cognitive outcomes and psychological symptoms in an Italian cohort with post-acute COVID-19 condition (PACC)

BackgroundWe aim to investigate the proportion of patients (pts) with long-term cognitive outcomes (CO) of PACC and identify associated features. MethodsWe assessed participants through a neuropsychological assessment. The chi-square test was used for comparisons according with time of NPA (within or beyond 6 months since COVID19) and with previously hospitalization status (hospitalized patients, PH; not hospitalized patients, nPH). Results520 participants: mean age 54 years (SD 12), 53 % female, 14 years of education (SD 3.4), 35 % with >1 comorbidity, 48 % previously hospitalized. Overall, we found CO in 89 % of pts, in particular 88 % evaluated in w6M and 89 % in b6M (p = 0.801) while 90 % and 87 % in nPH and PH, respectively (p = 0.239). By fitting multivariable analysis, PH for COVID19 and female gender were associated with an increased risk of an altered PSQI [Odd Ratio, OR 2.48, 95 % CI 1.54 to 3.99, p < 0.001 and OR 2.59, 95 % CI 1.60 to 4.17, p < 0.001, respectively) and BAI [F vs M: OR 1.67, 95 % CI 1.16 to 2.40, p = 0.005). ConclusionsWe show a substantial proportion of PACC-CO; hospitalization leads to impaired memory, anxiety and sleep disorders. Women seem to be at higher risk for anxious-depressive symptoms and worse sleep quality than men.

Joint administration of sub-threshold doses of the acetylcholinesterase inhibitor donepezil with those of the NMDA receptor antagonist ketamine improved rats’ recognition memory abilities

Alzheimer’s Disease (AD) is a serious progressive neurodegenerative illness conducting to the decay of cognitive functions. A few drugs have been approved for the therapy of AD, including the acetylcholinesterase inhibitors (AChEIs) like donepezil. Their efficiency, however, is modest and their application is associated with toxicity. Recently, the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, a rapidly acting antidepressant, has been proposed as a potential agent for the treatment of AD. The present study was designed to investigate the effects exerted by the combination of sub-threshold doses of donepezil with those of ketamine on rats’ recognition memory abilities. For these experiments, the object recognition task (ORT) and the object location task (OLT), two procedures assessing non-spatial and spatial recognition memory respectively in rodents were used. Post-training acute administration of inactive doses of donepezil (0.3 mg/kg) and ketamine (1 mg/kg) counteracted non-spatial and spatial recognition memory impairments. The present findings, although preliminary, propose that the combined administration of ketamine and donepezil could represent a new strategy for the therapy of memory disorders, a common feature of AD patients.

Suspected Pseudobulbar Affect in Neurodegenerative Disease.

To investigate the association between suspected pseudobulbar affect (PBA), clinical diagnosis, cognitive testing, and self-reported mood in older adults presenting for evaluation of dementia. Patients presenting to an outpatient memory disorders clinic (N=311). We used traditional and novel network modeling approaches to examine associations between neuropsychological (NP) tests, patient and clinician rating scales, and the Center for Neurological Study-Lability Scale (CNS-LS) among patients with suspected AD (n=133) and other neurocognitive diagnosis (n=178). We then examined differences in test performance between patients with and without suspected PBA (CNS-LS cut-off of ≥ 13), while accounting for demographic and psychiatric covariates with propensity score matching. Group differences were assessed with Bayesian models. Prevalence of suspected PBA in AD was slightly less than half (44.4%) and at a similar rate in other dementias (e.g., 46.9% in CVD and 45.5% in LBD). In network models, the CNS-LS was associated with higher anxiety and better word list recall. After accounting for covariates, AD patients with suspected PBA performed better on word list recall βM=0.40, 95% CI [0.15, 0.66], and committed fewer false positive errors on recognition βM=-1.51, 95% CI [-2.34, -0.59] than AD patients without suspected PBA. There were no differences in patients with any other diagnostic impression, nor group differences on other NP measures. Patients with suspected PBA and AD diagnosis had better memory recall and recognition than those without suspected PBA, suggesting that impaired emotional regulation may be an early sign of AD in patients with less prominent memory decline. Better understanding PBA in neurodegenerative diseases, including prevalence and comorbidity with psychiatric conditions, could help with early identification, education, and initiation of treatment.

Role of microglia polarization induced by glucose metabolism disorder in the cognitive impairment of mice from PM2.5 exposure

Studies have found that PM2.5 can damage the brain, accelerate cognitive impairment, and increase the risk of developing a variety of neurodegenerative diseases. However, the potential molecular mechanisms by which PM2.5 causes learning and memory problems are yet to be explored. In this study, we evaluated the neurotoxic effects in mice after 12 weeks of PM2.5 exposure, and found that this exposure resulted in learning and memory disorders, pathological brain damage, and M1 phenotype polarization on microglia, especially in the hippocampus. The severity of this damage increased with increasing PM2.5 concentration. Proteomic analysis, as well as validation results, suggested that PM2.5 exposure led to abnormal glucose metabolism in the mouse brain, which is mainly characterized by significant expression of hexokinase, phosphofructokinase, and lactate dehydrogenase. We therefore administered the glycolysis inhibitor 2-deoxy-d-glucose (2-DG) to the mice exposed to PM2.5, and showed that inhibition of glycolysis by 2-DG significantly alleviated PM2.5-induced hippocampal microglia M1 phenotype polarization, and reduced the release of inflammatory factors, improved synaptic structure and related protein expression, which alleviated the cognitive impairment induced by PM2.5 exposure. In summary, our study found that abnormal glucose metabolism-mediated inflammatory polarization of microglia played a role in learning and memory disorders in mice exposed to PM2.5. This study provides new insights into the neurotoxicity caused by PM2.5 exposure, and provides some theoretical references for the prevention and control of cognitive impairment induced by PM2.5 exposure.

First Demonstration of In Vivo PDE11A4 Target Engagement for Potential Treatment of Age-Related Memory Disorders.

PDE11A4 is a target of interest for the treatment of age-related memory disorders. A previous report from our laboratories described an amide series of potent, selective PDE11A4 inhibitors that was metabolically unstable. Investigation of heterocyclic amide isosteres for the labile amide moiety revealed distinct structure-activity relationships and identified several compounds with potency comparable to the amide series. This manuscript describes the characterization of structure-activity and structure-property relationships in this set, leading to the identification of an orally bioavailable, brain-penetrant, selective and potent PDE11A4 inhibitor. Target engagement experiments demonstrated PDE11A4 inhibition in the hypothalamus of mice that was absent in PDE11A4 knock out animals.

Episodic Memory and Posttraumatic Stress Disorder in Non-human Animals: A Methodological Proposal

The traditional conception of episodic memory, as a capacity that enables the conscious and personal re-experience of a past event, has led to methodological difficulties in attributing it to non-linguistic beings. The present work proposes to study the attribution of this capacity in non-human animals based on animal models of post-traumatic stress disorder (PTSD). For this purpose, evidence is presented suggesting that flashbacks, a characteristic symptom of PTSD, are a product of the episodic memory system. If that is true, then the ability to remember episodes is required to develop PTSD and having PTSD would be a compelling reason for attributing episodic memories. In this way, the present work opens a new field of research on the problem of episodic memory attribution in animals.

Abnormal resting-state functional connectivity of hippocampal subregions in type 2 diabetes mellitus-associated cognitive decline.

Type 2 diabetes mellitus (T2DM) over time predisposes to inflammatory responses and abnormalities in functional brain networks that damage learning, memory, or executive function. The hippocampus is a key region often reporting connectivity abnormalities in memory disorders. Here, we investigated peripheral inflammatory responses and resting-state functional connectivity (RSFC) changes characterized of hippocampal subregions in type 2 diabetes-associated cognitive decline (T2DACD). The study included 16 patients with T2DM, 16 patients with T2DACD and 25 healthy controls (HCs). Subjects were assessed for cognitive performance, tested for the expression of inflammatory factors IL-6, IL-10 and TNF-α in peripheral serum, underwent resting-state functional magnetic resonance imaging scans, and analyzed for RSFC using the hippocampal subregions as seeds. We also calculated the correlation between cognitive performance and RSFC of hippocampal subregion, and analyzed the significantly altered RSFC values of T2DACD for Receiver Operating Characteristic (ROC) analysis. T2DACD patients showed a decline in their ability to complete cognitive assessment scales and experimental paradigms, and T2DM did not show abnormal cognitive performance. IL-6 expression was increased in peripheral serum in both T2DACD and T2DM. Compared with HCs, T2DACD showed abnormalities RSFC of the left anterior hippocampus with left precentral gyrus and left angular gyrus. T2DM showed abnormalities RSFC of the left middle hippocampus with right medial frontal gyrus, right anterior and middle hippocampus with left precuneus, left anterior hippocampus with right precuneus and right posterior middle temporal gyrus. Compared with T2DM, T2DACD showed abnormalities RSFC of the left posterior hippocampus and right middle hippocampus with left precuneus. In addition, RSFC in the left posterior hippocampus with left precuneus of T2DACD was positively correlated with Flanker conflict response time (r=0.766, P=0.001). In the ROC analysis, the significantly altered RSFC values of T2DACD achieved significant performance. T2DACD showed a significant decrease in attentional inhibition and working memory, peripheral pro-inflammatory response increased, and abnormalities RSFC of the hippocampal subregions with default mode network and sensory-motor network. T2DM did not show a significant cognitive decline, but peripheral pro-inflammatory response increased and abnormalities RSFC of the hippocampus subregions occurred in the brain. In addition, the left precuneus may be a key brain region in the conversion of T2DM to T2DACD. The results of this study may provide a basis for the preliminary diagnosis of T2DACD.

Carvacrol improves cognitive dysfunction by decreasing amyloid-β accumulation and regulating neuroinflammation in ovariectomized renovascular hypertensive rats.

Hypertension contributes to both the development and progression of brain damage and cognitive dysfunction in the postmenopausal period in women. Carvacrol (CAR), which can easily cross the blood-brain barrier, exhibits neuroprotective properties due to its antioxidant, anti-inflammatory, and anti-apoptotic effects. In the present study, we have examined the effect of CAR treatment on learning-memory impairment in a post-menopausal hypertensive rat model that was induced by ovariectomy following two-kidney, one-clip renovascular hypertension surgery. From the third week after the establishment of renovascular hypertension in ovariectomized rats, CAR (40 mg/kg) was administered once daily for consecutive 7 weeks by gastric gavage. Systolic blood pressure was estimated by the tail-cuff method once a week. At the end of the study, cognitive functions were evaluated with behavioral tests and also neurochemical changes were measured in serum, cortex, and hippocampus by ELISA test. Blood pressure was decreased with CAR treatment in hypertensive rats. Serum estrogen levels decreased in ovariectomized rats and did not change with CAR treatment. CAR demonstrated beneficial effects on learning and memory tests as determined by increased recognition index, the number of platforms crossed, and time spent in the target quadrant. Due to CAR treatment, there was a marked reduction in the hippocampal and cortex amyloid-β, osteopontin, interleukin-6 and tumor necrosis factor-alpha levels, and acetylcholinesterase activity, while an increment in neprilysin and interleukin-10 levels was found. In conclusion, since CAR suppressed amyloid-β deposition and neuroinflammation in ovariectomized-hypertensive rats, it is thought that it may be protective against memory disorders in postmenopausal hypertensive women.

A - 4 The Potential Applications of Software Supporting the Early Detection of Cognitive Disorders and Dementia in Diagnostics and Prevention

Abstract Objective In Hungary, the process of diagnosing dementia is slow and time-consuming. Currently, there are no well-developed systems and strategies at the local level for screening, and there is no artificial intelligence algorithm that could determine early signs of dementia based on the patient’s digital behavioral patterns. Methods Two PILOTs were conducted using the PreDem platform. Over the PILOTs’ duration (2021.09.01.-2024.04.09), 61,902 test data were analyzed. The 259 participants completed SDMT-type tests, Stroop tests, and memory/word games. Results We established a unified system for task evaluation, facilitating cross-test result comparisons. Participants (n = 43,902) were grouped into three categories: 1st - presumed dementia patients (13,932), 2nd - diagnosed MS patients (16,175), and 3rd - presumably normal population (13,795). Comparing the first two groups to the normal population revealed significant differences, vividly illustrated by density functions. A key finding is the substantial improvement in individuals dealing with memory disorders and forgetfulness through regular cognitive game performance. Conclusion Study results reveal the PreDem platform’s potential as a valuable tool for early dementia detection and prevention. Combining cognitive tests and artificial intelligence, the platform can successfully identify early signs of dementia and cognitive impairment (90% accuracy), potentially leading to early diagnosis, treatment, and improved quality of life for patients and families.