Treatment Of Cognitive Disorders Research Articles

INNOVATIVE TECHNOLOGY FOR THE TREATMENT OF COGNITIVE DISORDERS

The authors digitized therapeutic factors used in the treatment of various forms of cognitive disorders, including dementia, with the subsequent development of a medical information system «Diagnosis and treatment of cognitive disorders». The medical information system «Diagnosis and treatment of cognitive disorders» was created on the basis of the 1C platform, supplemented by the module «Treatment of cognitive disorders», focused on supporting medical decision-making when choosing therapeutic factors for patients with cognitive disorders. It is planned to use this module in the complex activities of memory impairment classrooms.

Exposing Students to a Multi-Disciplinary Approach for Assessment and Treatment of Cognitive Disorders

Exposing Students to a Multi-Disciplinary Approach for Assessment and Treatment of Cognitive Disorders

Therapeutic Potential for Metabotropic Glutamate Receptor 7 Modulators in Cognitive Disorders.

Metabotropic glutamate receptor 7 (mGlu7) is the most highly conserved and abundantly expressed mGlu receptor in the human brain. The presynaptic localization of mGlu7, coupled with its low affinity for its endogenous agonist, glutamate, are features that contribute to the receptor's role in modulating neuronal excitation and inhibition patterns, including long-term potentiation, in various brain regions. These characteristics suggest that mGlu7 modulation may serve as a novel therapeutic strategy in disorders of cognitive dysfunction, including neurodevelopmental disorders that cause impairments in learning, memory, and attention. Primary mutations in the GRM7 gene have recently been identified as novel causes of neurodevelopmental disorders, and these patients exhibit profound intellectual and cognitive disability. Pharmacological tools, such as agonists, antagonists, and allosteric modulators, have been the mainstay for targeting mGlu7 in its endogenous homodimeric form to probe effects of its function and modulation in disease models. However, recent research has identified diversity in dimerization, as well as trans-synaptic interacting proteins, that also play a role in mGlu7 signaling and pharmacological properties. These novel findings represent exciting opportunities in the field of mGlu receptor drug discovery and highlight the importance of further understanding the functions of mGlu7 in complex neurologic conditions at both the molecular and physiologic levels. SIGNIFICANCE STATEMENT: Proper expression and function of mGlu7 is essential for learning, attention, and memory formation at the molecular level within neural circuits. The pharmacological targeting of mGlu7 is undergoing a paradigm shift by incorporating an understanding of receptor interaction with other cis- and trans- acting synaptic proteins, as well as various intracellular signaling pathways. Based upon these new findings, mGlu7's potential as a drug target in the treatment of cognitive disorders and learning impairments is primed for exploration.

Applications of Artificial Intelligence in the Neuropsychological Assessment of Dementia: A Systematic Review.

In the context of advancing healthcare, the diagnosis and treatment of cognitive disorders, particularly Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD), pose significant challenges. This review explores Artificial Intelligence (AI) and Machine Learning (ML) in neuropsychological assessment for the early detection and personalized treatment of MCI and AD. The review includes 37 articles that demonstrate that AI could be an useful instrument for optimizing diagnostic procedures, predicting cognitive decline, and outperforming traditional tests. Three main categories of applications are identified: (1) combining neuropsychological assessment with clinical data, (2) optimizing existing test batteries using ML techniques, and (3) employing virtual reality and games to overcome the limitations of traditional tests. Despite advancements, the review highlights a gap in developing tools that simplify the clinician's workflow and underscores the need for explainable AI in healthcare decision making. Future studies should bridge the gap between technical performance measures and practical clinical utility to yield accurate results and facilitate clinicians' roles. The successful integration of AI/ML in predicting dementia onset could reduce global healthcare costs and benefit aging societies.

Exploring the memory: existing activity-dependent tools to tag and manipulate engram cells.

The theory of engrams, proposed several years ago, is highly crucial to understanding the progress of memory. Although it significantly contributes to identifying new treatments for cognitive disorders, it is limited by a lack of technology. Several scientists have attempted to validate this theory but failed. With the increasing availability of activity-dependent tools, several researchers have found traces of engram cells. Activity-dependent tools are based on the mechanisms underlying neuronal activity and use a combination of emerging molecular biological and genetic technology. Scientists have used these tools to tag and manipulate engram neurons and identified numerous internal connections between engram neurons and memory. In this review, we provide the background, principles, and selected examples of applications of existing activity-dependent tools. Using a combination of traditional definitions and concepts of engram cells, we discuss the applications and limitations of these tools and propose certain developmental directions to further explore the functions of engram cells.

Center of Alzheimer’s Disease in Beijing, China

AbstractInnovation Center of Neurological Disorders (ICND) at Xuanwu Hospital, Capital Medical University in Beijing was found in 2015 by Prof. Jianping Jia. The center follows the integrated research paradigm, called “cognitive unit”, which includes memory clinics, laboratories, and research wards. This unit facilitates the comprehensive diagnosis and treatment of cognitive disorders, and helps improve the quality of dementia research. There are 82 researchers, lab technicians and clinicians in the center, plus ∼20 graduate students and over 40 visiting/trainee doctors. We carry out research focusing on mechanisms, drug development and peripheral biomarkers of Alzheimer’s disease (AD) and related dementias. Our center leads several large national multicenter cohort studies, including the Chinese familial Alzheimer’s Network (CFAN), the China Cognition and Aging Study (China COAST), the Study on Biomarkers for Early Diagnosis of Alzheimer’s Disease (Bio‐AD), and the Dementia Cohort Project of “China Brain Initiative 2030”. Prof. Jia, the director of the center, is the PI of nearly 30 national and international multicenter clinical trials on drug development, and the 2021 recipient of the Zaven Khachaturian Award.The Center promotes multidisciplinary research on AD and related dementias. We collect extensive clinical data and biological samples, standardize the inclusion/exclusion criteria, establish large‐sample dataset and biobanks, provide advanced training for AD specialists, generate national guidelines on dementia management, train exchanging students and visiting scholars, and organize national and international dementia and Alzheimer’s conferences. Research findings from the center have impact on national health strategies, and help policymakers to establish public health strategies, and develop individualized and precision interventions. As an example, Prof. Jia established the large national Alzheimer patients cohorts to examine the genetic, biofluid, imaging and domain‐specific cognitive markers, and underling mechanisms. The Center encourages data sharing, exchanging ideas, and discussing possible solutions based on the mutual scientific questions and clinical problems, as well as the existing differences from each country.International Alzheimer’s Research Centers can collaborate on global initiatives for establishing international AD cohorts, screening tools and techniques to evaluate the diagnostic utility of biomarkers, and to initiate global multicenter clinical trials.

Licochalcone A: A Potential Multitarget Drug for Alzheimer's Disease Treatment.

Licochalcone A (Lico-A) is a flavonoid compound derived from the root of the Glycyrrhiza species, a plant commonly used in traditional Chinese medicine. While the Glycyrrhiza species has shown promise in treating various diseases such as cancer, obesity, and skin diseases due to its active compounds, the investigation of Licochalcone A's effects on the central nervous system and its potential application in Alzheimer's disease (AD) treatment have garnered significant interest. Studies have reported the neuroprotective effects of Lico-A, suggesting its potential as a multitarget compound. Lico-A acts as a PTP1B inhibitor, enhancing cognitive activity through the BDNF-TrkB pathway and exhibiting inhibitory effects on microglia activation, which enables mitigation of neuroinflammation. Moreover, Lico-A inhibits c-Jun N-terminal kinase 1, a key enzyme involved in tau phosphorylation, and modulates the brain insulin receptor, which plays a role in cognitive processes. Lico-A also acts as an acetylcholinesterase inhibitor, leading to increased levels of the neurotransmitter acetylcholine (Ach) in the brain. This mechanism enhances cognitive capacity in individuals with AD. Finally, Lico-A has shown the ability to reduce amyloid plaques, a hallmark of AD, and exhibits antioxidant properties by activating the nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator of antioxidant defense mechanisms. In the present review, we discuss the available findings analyzing the potential of Lico-A as a neuroprotective agent. Continued research on Lico-A holds promise for the development of novel treatments for cognitive disorders and neurodegenerative diseases, including AD. Further investigations into its multitarget action and elucidation of underlying mechanisms will contribute to our understanding of its therapeutic potential.

The fibroblast growth factor system in cognitive disorders and dementia.

Cognitive impairment is the core precursor to dementia and other cognitive disorders. Current hypotheses suggest that they share a common pathological basis, such as inflammation, restricted neurogenesis, neuroendocrine disorders, and the destruction of neurovascular units. Fibroblast growth factors (FGFs) are cell growth factors that play essential roles in various pathophysiological processes via paracrine or autocrine pathways. This system consists of FGFs and their receptors (FGFRs), which may hold tremendous potential to become a new biological marker in the diagnosis of dementia and other cognitive disorders, and serve as a potential target for drug development against dementia and cognitive function impairment. Here, we review the available evidence detailing the relevant pathways mediated by multiple FGFs and FGFRs, and recent studies examining their role in the pathogenesis and treatment of cognitive disorders and dementia.

Use of SGLT2 inhibitors in the treatment of cognitive disorders

Background:Dementia is a progressive and irreversible disease entity that affects memory, verbal fluency, thinking and the performance of daily activities.The most common type of dementia is alzheimer's disease(AD).Currently, there are no specific therapies with established efficacy against cognitive decline or AD.Objective:The aim of this study is to summarize the current knowledge about the effectiveness of SGLT2 inhibitors(SGLT2i) in the treatment of cognitive disorders.Method and material:The article was created based on the PubMed database and the Polish Journal of Endocrinology.Articles were searched in English using the following keywords: SGLT2ihibitors;dementia;Alzheimer type 3 diabetes mellitus.State of knowledge:Patients with type 2 diabetes (TD2) are 1.5-2 times more likely to develop dementia than the general population.Dementia among diabetic patients is characterized by an earlier age of onset, slightly worse overall cognitive status and a higher prevalence of cognitive impairment in male patients.Diabetes and pre-diabetes shorten the time from the onset of mild cognitive impairment (MCI) to the development of full-blown dementia.Conclusions:The use of SGLT2i is associated with reduced mortality from dementia, in contrast to insulin and sulfonylurea derivatives.SGLT2 inihibitors prevent cognitive impairment more potently than dipeptidylpeptidase-4 inhibitors. Taking empagliflozin for one month, is associated with improved cognitive function and increased scores on the Montreal Cognitive Assessment scale.

Assessing preparedness for Alzheimer disease-modifying therapies in Australasian health care systems.

Assessing preparedness for Alzheimer disease-modifying therapies in Australasian health care systems.

Chinese clinical practice guidelines for digital memory clinic

Digital memory clinic aims to strengthen the early prevention and treatment of cognitive disorders by applying electronic assessment tools and digital auxiliary equipment to the management of cognitive disorders and sharing the information of the diagnosis and treatment from the hospitals at all levels. This guideline systematically retrieved and evaluated the effectiveness evidence related to the appropriate candidates of the digital memory clinic and the evaluation tools in various application scenarios, and recommended corresponding construction schemes for equipment configuration, personnel allocation and work flow suitable for the hospitals at all levels. Based on the empirical research and clinical practice in recent years, this guideline standardizes the selection of evaluation tools in various scenarios in the construction of digital memory outpatient clinic, refines the use of digital evaluation equipment, and clearly puts forward the responsibilities that hospitals at all levels should undertake. Release of this guideline will prompt the construction of digital memory outpatient department in hospitals at all levels, standardize the whole-process disease management for cognitive impairment patients and its high-risk groups (including combining reception, referral, intervention and follow-up), and extremely improve the efficiency of diagnosis and treatment of cognitive impairment.

Pathogenetic therapy of cognitive impairment: results of a multicenter placebo-controlled clinical trial of the efficacy and safety of Miladean

Evaluation of the efficacy and safety of the use of the drug Miladean in the treatment of patients with cognitive disorders (CDs) of vascular genesis. In during the double-blind multicenter prospective randomized placebo-controlled phase III clinical trial, 300 patients with CDs and chronic cerebral ischemia were randomized into 3 groups: group 1 (n=100) received Miladean (daily dose: memantine 10 mg + melatonin 6 mg), group 2 (n=101) - memantine (10 mg/day), group 3 - placebo (n=99) for 8 weeks. The dynamics of the overall score (the primary criterion of effectiveness) and the proportion of patients with improvement on the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog), the dynamics of visual-spatial orientation disorders (Benton test), sleep quality (Pittsburgh Sleep Quality Index scale) and the safety of therapy were evaluated. Miladean demonstrated efficacy in the treatment of CDs: a statistically and clinically significant decrease in the overall score on the ADAS-Sod scale was shown (by 6.1 versus 4.7 and 3.5 points in the 2nd (p=0.009) and 3rd (p<0.05) groups) and an increase in the proportion of patients (96.9%) with clinically and statistically a significant improvement compared to the 2nd and 3rd groups (p=0.019 and p<0.001 respectively). Miladean significantly improved the performance in the Benton test (1.20±1.66 vs. 0.64±1.69 points in group 3, p=0.026) and sleep quality (84.7% of patients with CDs), compared to placebo (63.9%) and memantine (64.3%) (p=0.002 in both cases). Miladean was well tolerated, there were no cases of interaction with basic therapy drugs. The combination of many different pathogenetic effects of Miladean suggests that it has the ability to slow down the rate of progression of CDs and stabilize the condition of patients. The unique combination of active substances in Miladean has been proven to be effective and safe in the treatment of patients with CDs.

Intelligent BCI Headphone for a Healthier and a Deeper Immersive Gameplay

The developments in the area of brain research by analysing brain activity of individuals have given rise to many useful applications, such as diagnosing mental disorders more efficiently, treatment of cognitive disorders, and developing of brain-computer interfaces for treatment, communication and entertainment purposes. However, the development of such applications is hindered by a shortage of easy-to-use and comfortable sensors, as well as a lack of high-quality brain activity data. In the first part of this paper, a review of the status of BCI applications is presented followed by a proposal of a framework for developing an intelligent BCI headphone that takes leverages of the huge amount of data coming from playing video games to let the players experience a full immersive gaming experience.

Assessment of hypolipidemic and anti-inflammatory properties of walnut (Juglans regia) seed coat extract and modulates some metabolic enzymes activity in triton WR-1339-induced hyperlipidemia in rat kidney, liver, and heart.

Atherosclerosis and cognitive impairment are both influenced by hyperlipidemia. Due to their high margin of safety and low cost, natural chemicals have recently attracted particular attention in the context of the treatment of disease. Hence, the purpose of this study was to investigate the possible amendatory impact of ethanol extract walnut (Juglans regia) seed coat (E-WSC) on some metabolic enzymes (glutathione reductase (GR), paraoxonase-1 (PON1), aldose reductase (AR), sorbitol dehydrogenase (SDH), acetylcholinesterase (AChE), glutathione S-transferase (GST), and butyrylcholinesterase (BChE)) activity in the liver, kidney, and heart of rats with Triton WR-1339-induced hyperlipidemia. Rats were divided into five groups: control group, HL-Control group (Triton WR-1339 400 mg/kg, i.p administered group), E- WSC + 150 (150 mg/kg,o.d given group), E- WSC + 300 (E- WSC 300 mg/kg, o.d given group) and HL+ E-WSC + 300 (Group receiving E- WSC 300 mg/kg, o.d 30 min prior to administration of Triton WR-1339 400 mg/kg, i.p). In HL-Control, AR, SDH, and BChE enzyme activity was significantly increased in all tissues compared to the control, while the activity of other studied enzymes was significantly decreased. The effects of hyperlipidemia on balance were improved and alterations in the activity of the investigated metabolic enzymes were prevented by E-WSC. As a result, promising natural compounds that can be used as adjuvant therapy in the treatment of cognitive disorders and hyperlipidemia may be found in E-WSC powder.

Vitamin D3 supplementation ameliorates cognitive impairment and alters neurodegenerative and inflammatory markers in scopolamine induced rat model.

A multifaceted approach can be effective for the treatment of dementia including the most common form, Alzheimer's disease (AD). However, currently, it involves only symptomatic treatment with cholinergic drugs. Beneficial effects of high Vitamin D3 levels or its intake in the prevention and treatment of cognitive disorders have been reported. Thus, the present study examined the preventive effect of Vitamin D3 (Calcitriol) supplementation on cognitive impairment and evaluated its impact on the accumulation or degradation of Aβ plaques. A single intraperitoneal injection of scopolamine was used to induce cognitive impairment in rats. Treatment of Vitamin D3 was provided for 21days after the injection. Various behavioral parameters like learning, spatial memory and exploratory behavior, biochemical alterations in the brain homogenate and histology of the hippocampus were investigated. Our results indicated that scopolamine-induced rats depicted cognitive deficits with high Aβ levels and hyperphosphorylated tau proteins in the brain tissue, while Vitamin D supplementation could significantly improve the cognitive status and lower these protein levels. These results were supported by the histopathological and immunohistochemical staining of the hippocampal brain region. Furthermore, mechanistic analysis depicted that Vitamin D supplementation improved the Aβ protein clearance by increasing the neprilysin levels. It also reduced the accumulation of Aβ plaques by lowering neuroinflammation as well as oxidative stress. The present findings indicate that Vitamin D3 supplementation can ameliorate cognitive deficits and thereby delay AD progression by increasing Aβ plaque degradation, reducing inflammation and oxidative stress.

Protective Effects of Pioglitazone on Cognitive Impairment and the Underlying Mechanisms: A Review of Literature.

Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, is known to have anti-inflammatory and anti-oxidant effects on the brain, and its clinical potential in the treatment of cognitive impairment in diseases such as Alzheimer's disease (AD) and Parkinson disease (PD) is currently being explored. This review focused on the reported beneficial effects of pioglitazone on cognitive dysfunction and summarized the associated mechanisms associated with pioglitazone-induced improvement in cognitive dysfunction. Our review of the relevant literature indicated that there is conclusive evidence of the effect of pioglitazone on improving cognitive impairment via its agonistic effect on PPAR-γ. Further, several mechanisms of action have been reported, and these include enhanced NF-kB and p38 activity; regulation of the pro-inflammatory cytokines IL-1, IL-6, and TNF-α; inhibition of Aβ production; alterations in the levels of mitochondrial proteins such as mitoNEET; regulation of protein kinases such as CDK5 and JNK; regulation of ROS and MDA levels and the levels of the antioxidant proteins TRX1 and PON2; and increased expression of thyroid hormone receptors. Despite these promising findings, pioglitazone treatment is also associated with cardiovascular risks, such as weight gain and edema, which subsequently increase the risk of mortality. Further, it has been documented that pioglitazone may be unable to cross the blood–brain barrier when administered in certain forms, and it can also cause cell death when administered at high concentrations. Therefore, further research is required to explore the effects of acute and chronic pioglitazone treatment on memory function and the associated risks, in order to determine its clinical applicability in the treatment of cognitive disorders. Nonetheless, the current literature does demonstrate that pioglitazone promotes the function of PPAR receptors in ameliorating inflammation, oxidative stress, amyloidogenesis, and hypothyroidism, and enhancing neurogenesis, synaptic plasticity, and mitochondrial function. Therefore, these mechanisms of PPAR receptors warrant further investigation in order to establish the clinical applicability of pioglitazone in the treatment of cognitive disorders, such as PD and AD, and neuronal impairment in conditions such as diabetes.

Comprehensive interdisciplinary and interdepartmental program for prevention, early detection, diagnosis and treatment of cognitive disorders in older and senile people

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Cross state-dependent memory retrieval between cannabinoid CB1 and serotonergic 5-HT1A receptor agonists in the mouse dorsal hippocampus

Understanding the neurobiological mechanisms of drug-related learning and memory formation may help the treatment of cognitive disorders. Dysfunction of the cannabinoid and serotonergic systems has been demonstrated in learning and memory disorders.The present paper investigates the phenomenon called state-dependent memory (SDM) induced by ACPA (a selective cannabinoid CB1 receptor agonist) and 8-OH-DPAT (a nonselective 5-HT1A receptor agonist) with special focus on the role of the 5-HT1A receptor in the effects of both ACPA and 8-OH-DPAT SDM and cross state-dependent memory retrieval between ACPA and 8-OH-DPAT in a step-down inhibitory avoidance task.The dorsal hippocampal CA1 regions of adult male NMRI mice were bilaterally cannulated, and all drugs were microinjected into the intended injection sites. A single-trial step-down inhibitory avoidance task was used to assess memory retrieval and state-dependence.Post-training and/or pre-test microinjections of ACPA (1 and 2 ng/mouse) and 8-OH-DPAT (0.5 and 1 μg/mouse) dose-dependently induced amnesia. Pre-test administration of the same doses of ACPA and 8-OH-DPAT reversed the post-training ACPA- and 8-OH-DPAT-induced amnesia, respectively. This phenomenon has been named SDM. 8-OH-DPAT (1 μg/mouse) reversed the amnesia induced by ACPA (0.5, 1, and 2 ng/mouse) and induced ACPA SDM. ACPA (2 ng/mouse) reversed the amnesia induced by 8-OH-DPAT (0.25, 0.5, and 1 μg/mouse) and induced 8-OH-DPAT SDM. Pre-test administration of a 5-HT1A receptor antagonist, (S)-WAY 100,135 (0.25 and 0.5 μg/mouse), 5 min before ACPA and 8-OH-DPAT dose-dependently inhibited ACPA- and 8-OH-DPAT-induced SDM, respectively.The present study results demonstrated ACPA- and 8-OH-DPAT- induced SDM. Overall, the data revealed that dorsal hippocampal 5-HT1A receptor mechanisms play a pivotal role in modulating cross state-dependent memory retrieval between ACPA and 8-OH-DPAT.

Activation of a Locus Coeruleus to Dorsal Hippocampus Noradrenergic Circuit Facilitates Associative Learning.

Processing of contextual information during a new episodic event is crucial for learning and memory. Neuromodulation in the hippocampus and prefrontal cortex plays an important role in the formation of associations between environmental cues and an aversive experience. Noradrenergic neurons in the locus coeruleus send dense projections to both regions, but their contribution to contextual associative learning has not been established. Here, we utilize selective optogenetic and pharmacological manipulations to control noradrenergic transmission in the hippocampus during the encoding of a contextual fear memory. We find that boosting noradrenergic terminal release in the dorsal CA1 enhances the acquisition of contextual associative learning and that this effect requires local activation of β-adrenenergic receptors. Moreover, we show that increasing norepinephrine release can ameliorate contextual fear learning impairments caused by dopaminergic dysregulation in the hippocampus. Our data suggest that increasing of hippocampal noradrenergic activity can have important implications in the treatment of cognitive disorders that involve problems in contextual processing.

COVID-19 in structure of risk factors for cognitive impairment, methods of correction

Cerebrovascular disorders are one of the main causes of cognitive impairment. Understanding the cause of vascular brain damage, establishing the existing risk factors allow choosing the optimal treatment strategy and slowing the progression of cognitive impairment. The article discusses information about risk factors for cognitive impairment: age, level of education, social isolation and lack of physical activity, excessive alcohol consumption, smoking, exposure to polluted air, hypertension, hearing loss, traumatic brain injury, diabetes mellitus, depression, cerebrovascular diseases, Alzheimer’s disease, genetic predisposition. Information is provided on the possible impact of COVID-19 on the development and progression of cognitive impairment. The possibilities of neurometabolic drugs in the treatment of cognitive disorders are considered. The results of the analysis of the experience of using the drug citicoline (Noocil) in the treatment of patients with cognitive impairment are presented, the possible advantages of prescribing Noocil in the form of a solution for oral administration are noted.