Alterations in Neuronal Nicotinic Acetylcholine Receptors in the Pathogenesis of Various Cognitive Impairments.

Cognitive impairment is a typical symptom of both neurodegenerative and certain other diseases. In connection with these different pathologies, the etiology and neurological and metabolic changes associated with cognitive impairment must differ. Until these characteristics and differences are understood in greater detail, pharmacological treatment of the different forms of cognitive impairment remains suboptimal. Neurotransmitter receptors, including neuronal nicotinic acetylcholine receptors (nAChRs), dopamine receptors, and glutamine receptors, play key roles in the functions and metabolisms of the brain. Among these, the role of nAChRs in the development of cognitive impairment has attracted more and more attention. The present review summarizes what is presently known concerning the structure, distribution, metabolism, and function of nAChRs, as well as their involvement in major cognitive disorders such as Alzheimer's disease, Parkinson's disease, vascular dementia, schizophrenia, and diabetes mellitus. As will be discussed, the relevant scientific literature reveals clearly that the α4ß2 and α7 nAChR subtypes and/or subunits of the receptors play major roles in maintaining cognitive function and in neuroprotection of the brain. Accordingly, focusing on these as targets of drug therapy can be expected to lead to breakthroughs in the treatment of cognitive disorders such as AD and schizophrenia.

An update on the cognitive safety of antimuscarinics in the treatment of overactive bladder.

INTRODUCTION: Antimuscarinics are often the first-choice medications used to treat overactive bladder (OAB), a condition that increasingly affects the aging population. However, concerns regarding their potential impact on cognitive function have persisted for more than a decade. AREAS COVERED: This review was conducted to update the literature on the cognitive safety profiles of various antimuscarinics, integrating findings from both recent and earlier studies to present an updated and comprehensive analysis. A search of English-language publications, including electronic databases and gray literature, focused on the cognitive impacts of antimuscarinics, resulting in a review and assessment of diverse studies and their associated outcomes. EXPERT OPINION: Oxybutynin requires caution due to potential adverse effects, suggesting a need to consider alternative therapies. Darifenacin, while promising in preserving cognitive function, warrants further investigation for use in dementia patients. Fesoterodine has shown tolerance without cognitive decline in controlled trials. However, Tolterodine and Solifenacin present conflicting evidence regarding cognitive impairment and dementia risk, respectively, necessitating additional research to ascertain their safety profiles. Careful monitoring and treatment of patients taking these medications for cognitive impairment are essential. Further research, particularly in vulnerable populations, is crucial to establish cognitive safety profiles of various antimuscarinics and inform optimal OAB treatment strategies.

The Profile of the Italian Centers for Cognitive Disorders and Dementia in the Context of New Drugs in Alzheimer's Disease.

Background: The wait for the upcoming disease-modifying therapies (DMT) for Alzheimer's disease in Europe is raising questions about the preparedness of national healthcare systems to conduct accurate diagnoses and effective prescriptions. In this article, we focus on the current situation in Italy. Objective: The primary goal is to propose a profile of the Italian Centers for Cognitive Disorders and Dementias (CCDDs) that could be taken into consideration by regional and autonomous provincial authorities when deciding on the prescribing centers for DMT. Methods: Based on responses to a national survey on CCDDs in Italy, we identified the CCDDs that meet the requirements for effective prescription: 1) Multidisciplinary team; 2) Minimum Core Test for the neuropsychological assessment; 3) PET, CSF, and Brain MRI assessments. Univariate and multivariate comparisons were conducted between CCDDs that met the criteria and the others. Results: Only 10.4% of CCDDs met the requirements for effective DMT prescription, mainly located in Northern Italy. They are also characterized by longer opening hours, a higher number of professionals, a university location, and a higher frequency of conducting genetic tests, and could potentially result in prescribing centers. Conclusions: The findings suggest that the Italian national healthcare system may benefit from further enhancements to facilitate the effective prescription of DMTs. This could involve initiatives to reduce fragmentation, ensure adequate resources and equipment, and secure sufficient funding to support this aspect of healthcare delivery.

BACE1 inhibitors from the fruits of Alpinia oxyphylla have efficacy to treat T2DM-related cognitive disorder.

The fruits of Alpinia oxyphylla (Alpiniae Oxyphyllae Fructus, AOF) are one of the "Four Famous South Medicines" in China. In this study, beta-site amyloid protein precursor cleaving enzyme 1 (BACE1) was applied to explore the active components in AOF responsible for type 2 diabetes mellitus (T2DM)-related cognitive disorder. As a result, 24 compounds including three unreported ones (1, 3, 4) were isolated from AOF. Compound 1 is an unusual carbon­carbon linked diarylheptanoid dimer, and compound 4 is the first case of 3,4-seco-eudesmane sesquiterpenoid with a 5/6-bicyclic skeleton. Four diarylheptanoids (3, 5-7), one flavonoid (9) and two sesquiterpenoids (14 and 20) showed BACE1 inhibitory activity, of which the most active 6 was revealed to be a non-competitive and anti-competitive mixed inhibitor. Docking simulation suggested that OH-4' of 6 played important roles in maintaining activity by forming hydrogen bonds with Ser36 and Ile126 residues. Compounds 3, 5, 9 and 20 displayed neuroprotective effects against amyloid ß (Aß)-induced damage in BV2 cells. Mechanism study revealed that compounds 5 and 20 downregulated the expression of BACE1 and upregulated the expression of Lamp2 to exert effects. Thus, the characteristic diarylheptanoids and sesquiterpenoids in AOF had the efficacy to alleviate T2DM-related cognitive disorder by inhibiting BACE1 activity and reversing Aß-induced neuronal damage.

Nimodipine Protects Vascular and Cognitive Function in an Animal Model of Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease is a common cause of vascular cognitive impairment and dementia. There is an urgent need for preventative treatments for vascular cognitive impairment and dementia, and reducing vascular dysfunction may provide a therapeutic route. Here, we investigate whether the chronic administration of nimodipine, a central nervous system-selective dihydropyridine calcium channel blocking agent, protects vascular, metabolic, and cognitive function in an animal model of cerebral small vessel disease, the spontaneously hypertensive stroke-prone rat. METHODS: Male spontaneously hypertensive stroke-prone rats were randomly allocated to receive either a placebo (n=24) or nimodipine (n=24) diet between 3 and 6 months of age. Animals were examined daily for any neurological deficits, and vascular function was assessed in terms of neurovascular and neurometabolic coupling at 3 and 6 months of age, and cerebrovascular reactivity at 6 months of age. Cognitive function was evaluated using the novel object recognition test at 6 months of age. RESULTS: Six untreated control animals were terminated prematurely due to strokes, including one due to seizure, but no treated animals experienced strokes and so had a higher survival (P=0.0088). Vascular function was significantly impaired with disease progression, but nimodipine treatment partially preserved neurovascular coupling and neurometabolic coupling, indicated by larger (P<0.001) and more prompt responses (P<0.01), and less habituation upon repeated stimulation (P<0.01). Also, animals treated with nimodipine showed greater cerebrovascular reactivity, indicated by larger dilation of arterioles (P=0.015) and an increase in blood flow velocity (P=0.001). This protection of vascular and metabolic function achieved by nimodipine treatment was associated with better cognitive function (P<0.001) in the treated animals. CONCLUSIONS: Chronic treatment with nimodipine protects from strokes, and vascular and cognitive deficits in spontaneously hypertensive stroke-prone rat. Nimodipine may provide an effective preventive treatment for stroke and cognitive decline in cerebral small vessel disease.

Structural characterization and improves cognitive disorder in ageing mice of a glucomannan from Dendrobium huoshanense.

In the present work, a neutral polysaccharide (DHP-2W) with attenuating cognitive disorder was identified from Dendrobium huoshanense and its structure was clarified. The polysaccharide was successfully purified from D. huoshanense by column chromatography and its activity was evaluated. With a molecular weight of 508.934kDa, this polysaccharide is composed of mannose and glucose at a molar ratio of 75.81: 24.19. Structural characterization revealed that DHP-2W has a backbone consisting of 4)-ß-D-Manp-(1 and 4)-ß-D-Glcp-(1. In vivo experiments revealed that DHP-2W improved cognitive disorder in D-galactose treated mice and relieved oxidative stress and inflammation. DHP-2W attenuates D-galactose-induced cognitive disorder by inhibiting the BCL2/BAX/CASP3 pathway and activating the AMPK/SIRT pathway, thereby inhibiting apoptosis. Furthermore, DHP-2W had a significant effect on regulating the serum levels of Flavin adenine dinucleotide, Shikimic acid, and Kynurenic acid in aged mice. These, in turn, had a positive impact on AMPK/SIRT1 and BCL2/BAX/CASP3, resulting in protective effects against cognitive disorder.

Prenatal treatment with preimplantation factor improves early postnatal neurogenesis and cognitive impairments in a mouse model of Down syndrome.

Down syndrome (DS) is a genetic disease characterized by a supernumerary chromosome 21. Intellectual deficiency (ID) is one of the most prominent features of DS. Central nervous system defects lead to learning disabilities, motor and language delays, and memory impairments. At present, a prenatal treatment for the ID in DS is lacking. Subcutaneous administration of synthetic preimplantation factor (sPIF, a peptide with a range of biological functions) in a model of severe brain damage has shown neuroprotective and anti-inflammatory properties by directly targeting neurons and microglia. Here, we evaluated the effect of PIF administration during gestation and until weaning on Dp(16)1Yey mice (a mouse model of DS). Possible effects at the juvenile stage were assessed using behavioral tests and molecular and histological analyses of the brain. To test the influence of perinatal sPIF treatment at the adult stage, hippocampus-dependent memory was evaluated on postnatal day 90. Dp(16)1Yey pups showed significant behavioral impairment, with impaired neurogenesis, microglial cell activation and a low microglial cell count, and the deregulated expression of genes linked to neuroinflammation and cell cycle regulation. Treatment with sPIF restored early postnatal hippocampal neurogenesis, with beneficial effects on astrocytes, microglia, inflammation, and cell cycle markers. Moreover, treatment with sPIF restored the level of DYRK1A, a protein that is involved in cognitive impairments in DS. In line with the beneficial effects on neurogenesis, perinatal treatment with sPIF was associated with an improvement in working memory in adult Dp(16)1Yey mice. Perinatal treatment with sPIF might be an option for mitigating cognitive impairments in people with DS.

Effectiveness of Psychobiotics in the Treatment of Psychiatric and Cognitive Disorders: A Systematic Review of Randomized Clinical Trials.

In this study, a systematic review of randomized clinical trials conducted from January 2000 to December 2023 was performed to examine the efficacy of psychobiotics-probiotics beneficial to mental health via the gut-brain axis-in adults with psychiatric and cognitive disorders. Out of the 51 studies involving 3353 patients where half received psychobiotics, there was a notably high measurement of effectiveness specifically in the treatment of depression symptoms. Most participants were older and female, with treatments commonly utilizing strains of Lactobacillus and Bifidobacteria over periods ranging from 4 to 24 weeks. Although there was a general agreement on the effectiveness of psychobiotics, the variability in treatment approaches and clinical presentations limits the comparability and generalization of the findings. This underscores the need for more personalized treatment optimization and a deeper investigation into the mechanisms through which psychobiotics act. The research corroborates the therapeutic potential of psychobiotics and represents progress in the management of psychiatric and cognitive disorders.

Inhibition of mannan-binding lectin associated serine protease (MASP)-2 reduces the cognitive deficits in a mouse model of severe traumatic brain injury.

The lectin pathway (LP) of complement mediates inflammatory processes linked to tissue damage and loss of function following traumatic brain injury (TBI). LP activation triggers a cascade of proteolytic events initiated by LP specific enzymes called MASPs (for Mannan-binding lectin Associated Serine Proteases). Elevated serum and brain levels of MASP-2, the effector enzyme of the LP, were previously reported to be associated with the severity of tissue injury and poor outcomes in patients with TBI. To evaluate the therapeutic potential of LP inhibition in TBI, we first conducted a pilot study testing the effect of an inhibitory MASP-2 antibody (α-MASP-2), administered systemically at 4 and 24 h post-TBI in a mouse model of controlled cortical impact (CCI). Treatment with α-MASP-2 reduced sensorimotor and cognitive deficits for up to 5 weeks post-TBI. As previous studies by others postulated a critical role of MASP-1 in LP activation, we conducted an additional study that also assessed treatment with an inhibitory MASP-1 antibody (α-MASP-1). A total of 78 mice were treated intraperitoneally with either α-MASP-2, or α-MASP-1, or an isotype control antibody 4 h and 24 h after TBI or sham injury. An amelioration of the cognitive deficits assessed by Barnes Maze, prespecified as the primary study endpoint, was exclusively observed in the α-MASP-2-treated group. The behavioral data were paralleled by a reduction of the lesion size when evaluated histologically and by reduced systemic LP activity. Our data suggest that inhibition of the LP effector enzyme MASP-2 is a promising treatment strategy to limit neurological deficits and tissue loss following TBI. Our work has translational value because a MASP-2 antibody has already completed multiple late-stage clinical trials in other indications and we used a clinically relevant treatment protocol testing the therapeutic mechanism of MASP-2 inhibition in TBI.

Hippocampal acetylcholinesterase activation induced by streptozotocin in mice is protected by an organotellurium compound without evidence of toxicity.

The cognitive deficit, which is like Alzheimer's disease and is associated with oxidative damage, may be induced by exposure to streptozotocin. This study aimed to evaluate if the tellurium-containing organocompound, 3j, 5'-arylchalcogeno-3-aminothymidine derivative, interferes with the effects of streptozotocin, as well as to investigate its toxicity in adult mice. Cognitive deficit was induced by two doses of streptozotocin (2.25 mg/kg/day, 48 h interval) intracerebroventricularly. After, the mice were subcutaneously treated with 3j (8.62 mg/kg/day) for 25 days. The effects were assessed by evaluating hippocampal and cortical acetylcholinesterase and behavioral tasks. 3j toxicity was investigated for 10 (0, 21.55, or 43.10 mg/kg/day) and 37 (0, 4.31, or 8.62 mg/kg/day) days by assessing biometric parameters and glucose and urea levels, and alanine aminotransferase activity in blood plasma. 3j exposure did not alter the behavioral alterations induced by streptozotocin exposure. On the other hand, 3j exposure normalized hippocampus acetylcholinesterase activity, which is enhanced by streptozotocin exposure. Toxicity evaluation showed that the administration of 3j for either 10 or 37 days did not cause harmful effects on the biometric and biochemical parameters analyzed. Therefore, 3j does not present any apparent toxicity and reverts acetylcholinesterase activity increase induced by streptozotocin in young adult mice.

[Asthenic disorders correction with Recognan]. / Korrektsiya astenicheskikh sostoyanii preparatom Rekognan.

Asthenia, asthenic syndrome, asthenic condition, asthenic reaction, asthenic disorders are terms that describe the state of «impotence¼. Fatigue that occurs against the background of habitual physical or intellectual stress for a person, and persists after rest, is asthenia. For people of the older age group, the term senile asthenia syndrome is used. Asthenia manifests itself with increased fatigue and exhaustion, mood instability, increased irritability, sleep disorders. Asthenic conditions manifest themselves along with a decrease in physical activity, increased cognitive and mental fatigue. Asthenic syndrome (AS) are considered as an integral part of cardiovascular diseases (CVD), as one of the manifestations of cerebrovascular pathology. Senile asthenia syndrome (SAS) is a geriatric syndrome characterized by an age-associated decrease in the physiological reserve and functions of many body systems, including cognitive functions. One of the drugs that has a positive effect on the severity of AS and improves the state of cognitive functions is the domestic drug Recognan (citicoline). The effectiveness of Recognan in the treatment of AS in patients with CVD, SAS, and post-COVID asthenia has been shown. It is recommended to prescribe Recognan orally at 500 mg / day for 30 days. Recognan has a nootropic and antiasthenic effect.

[Neurometabolic therapy of mild cognitive impairment in patients with chronic cerebral ischemia]. / Neirometabolicheskaya terapiya umerennykh kognitivnykh rasstroistv u patsientov s khronicheskoi ishemiei golovnogo mozga.

OBJECTIVE: To evaluate the effect of a sequential therapy regimen with Mexidol (500 mg injections intravenously for 14 days) and Mexidol FORTE 250 (250 mg tablets 3 times a day for 60 days) on higher cortical functions in patients with moderate cognitive disorders in chronic cerebral ischemia. MATERIAL AND METHODS: A comparative, prospective study included 63 patients with chronic cerebral ischemia with moderate cognitive impairment. All patients received basic therapy aimed at reducing risk factors (antihypertensive, antithrombotic drugs as indicated). Patients of the main group (30 people: 12 men, 18 women) received Mexidol intravenously 500 mg in 100 ml of 0.9% NaCl solution once a day for 14 days, then Mexidol FORTE 250 (film-coated tablets) 250 mg 3 times a day for the next 60 days. The comparison group consisted of 33 patients (14 men, 19 women) who received only basic therapy. The groups were comparable in terms of age, sex characteristics and severity of cognitive deficit. We examined cognitive status (MoCA scale, Frontal Dysfunction Battery, 10 Word Memorization tests), severity of asthenia (MFI-20 scale), anxiety and depression (HADS scale), patient's subjective assessment of the dynamics of the condition (CGI-improvement scale) in 1st, 14th and 74th±5 days of observation. On days 1 and 74±5 of observation, patients were examined using transcranial magnetic stimulation to study the neuronal activity of the cerebral cortex. RESULTS: In the main group, at the time of completion of taking Mexidol and Mexidol FORTE 250, a pronounced cognitive regression was noted (MoCA scale +3 points, difference with the comparison group 1 point (p<0.0001); Frontal Dysfunction Battery test +4 points, difference with comparison group 2 points (p<0.001); memory test «10 words¼ +2 points, difference with the comparison group 1 point (p<0.05), emotional (HADS anxiety scale -8 points, difference with the comparison group 3 points (p<0.001), depression -3.5 points, difference with the comparison group 1.5 points (p<0.01), asthenic disorders (MFI-20 scale -30 points, difference with the comparison group 15.5 points (p<0.01), improvement in the well-being of patients (CGI-improvement scale -2 points, difference with the comparison group 1 point (p<0.0001). According to the transcranial magnetic stimulation performed, a statistically significant decrease in the central motor conduction time at the level of 1 and 2 motor neurons of the pyramidal tract bilaterally from the start to the end of therapy with Mexidol and Mexidol FORTE 250 was determined (p<0.01). An inverse correlation was found between the time of central motor conduction and the results of the Frontal Dysfunction Battery test at the same time points with left-sided localization of 1 motor neuron (p<0.01). The results of a study of the use of sequential therapy with Mexidol 500 mg IV drip 1 time per day for 14 days followed by oral administration of Mexidol FORTE 250 1 tablet 3 times a day for 60 days indicate its clinical effectiveness and safety in patients with chronic cerebral ischemia with mild cognitive impairment, and also confirm its importance for preventing the progression of cognitive disorders.

(R)-ketamine restores anterior insular cortex activity and cognitive deficits in social isolation-reared mice.

Chronic social isolation increases the risk of mental health problems, including cognitive impairments and depression. While subanesthetic ketamine is considered effective for cognitive impairments in patients with depression, the neural mechanisms underlying its effects are not well understood. Here we identified unique activation of the anterior insular cortex (aIC) as a characteristic feature in brain-wide regions of mice reared in social isolation and treated with (R)-ketamine, a ketamine enantiomer. Using fiber photometry recording on freely moving mice, we found that social isolation attenuates aIC neuronal activation upon social contact and that (R)-ketamine, but not (S)-ketamine, is able to counteracts this reduction. (R)-ketamine facilitated social cognition in social isolation-reared mice during the social memory test. aIC inactivation offset the effect of (R)-ketamine on social memory. Our results suggest that (R)-ketamine has promising potential as an effective intervention for social cognitive deficits by restoring aIC function.

Association between serum insulin-like growth factor 1 levels and the improvements of cognitive impairments in a subgroup of schizophrenia: Preliminary findings.

BACKGROUND: Numerous studies have implicated abnormal insulin-like growth factor 1 (IGF-1) in the pathophysiology of schizophrenia, but findings have been inconsistent. METHODS: We conducted a meta-analysis to compare IGF-1 levels in schizophrenia patients with healthy controls and explored factors contributing to variability between estimates. In an independent sample (58 chronic schizophrenia patients and 30 healthy controls), we investigated differences in IGF-1 levels among schizophrenia subgroups with distinct cognitive profiles, identified using k-means clustering based on five cognitive domains from The Repeatable Battery for the Assessment of Neuropsychological Status. Associations between serum IGF-1 levels and clinical and neurocognitive improvements were also examined. RESULTS: The meta-analysis revealed significantly lower serum IGF-1 levels in schizophrenia patients compared to healthy controls, albeit with high heterogeneity. Medication status, BMI, and severity of negative symptoms were identified as potential contributors to this heterogeneity. In our independent study, antipsychotic treatment led to a significant increase in IGF-1 levels, and lower pre-treatment serum IGF-1 levels correlated with greater improvement in cognitive deficits, particularly in a subgroup with more severe cognitive symptoms. CONCLUSIONS: Our findings support the "IGF-1 deficiency hypothesis" in the pathogenesis of schizophrenia. Further research is crucial to elucidate the role of IGF-1 in the cognitive impairments associated with schizophrenia.

Therapeutic potential of curcumin on the cognitive decline in animal models of Alzheimer's disease: a systematic review and meta-analysis.

Curcumin, a polyphenol derived from the herb turmeric, has emerged as a prospective potential therapy in the treatment of Alzheimer's disease (AD). However, the efficacy of curcumin treatment in improving cognitive decline caused controversy recently. We aimed to systematically review the effect of curcumin on cognitive impairment in an animal model of AD. We conducted an exhaustive database search of related studies. Two investigators identified studies and independently extracted data. Stratified meta-analyses and meta-regression analyses were carried out to explore the sources of heterogeneity. Publication bias was assessed using funnel plots and Egger's test. Our systematic review included 33 articles. A meta-analysis of 29 publications showed that curcumin exerts significant positive effects on cognitive performance. For acquisition, the global estimated effect of curcumin was - 2.027 (95% CI - 2.435 to - 1.619, p < 0.001); for retention, the global estimated effect of curcumin was 1.606 (95% CI 1.101 to 2.111, p < 0.001). The stratified meta-analysis demonstrated that an increased effect size depended on diverse study characteristics. Additionally, publication bias was detected. We conclude that curcumin may reduce cognitive deficits in experimental AD. Furthermore, we emphasize that additional well-designed and well-reported animal studies are needed to inform further clinical studies.

Coconut oil ameliorates behavioral and biochemical alterations induced by D-GAL/AlCl3 in rats.

Alzheimer's disease (AD) is a chronic, progressive neurodegenerative condition marked by cognitive impairment. Although coconut oil has been shown to be potentially beneficial in reducing AD-related cognitive deficits, information on its mechanism of action is limited. Thus, we investigated the effects of coconut oil on spatial cognitive ability and non-cognitive functions in a rat model of AD induced by G-galactose (D-GAL) and aluminum chloride (AlCl3), and examined the changes in synaptic transmission, cholinergic activity, neurotrophic factors and oxidative stress in this process. The AD model was established by administering D-GAL and AlCl3 for 90 days, while also supplementing with coconut oil during this time. Cognitive and non-cognitive abilities of the rats were evaluated at the end of the 90-day supplementation period. In addition, biochemical markers related to the pathogenesis of the AD were measures in the hippocampus tissue. Exposure to D-GAL/AlCl3 resulted in a reduction in locomotor activity, an elevation in anxiety-like behavior, and an impairment of spatial learning and memory (P < 0.05). The aforementioned behavioral disturbances were observed to coincide with increased oxidative stress and cholinergic impairment, as well as reduced synaptic transmission and levels of neurotrophins in the hippocampus (P < 0.05). Interestingly, treatment with coconut oil attenuated all the neuropathological changes mentioned above (P < 0.05). These findings suggest that coconut oil shows protective effects against cognitive and non-cognitive impairment, AD pathology markers, oxidative stress, synaptic transmission, and cholinergic function in a D-GAL/AlCl3-induced AD rat model.

Cognitive impairment after recovery from COVID-19: Frequency, profile, and relationships with clinical and laboratory indices.

Cognitive impairment (CI) is regarded as a remarkable burden in COVID-19 survivors. Its prevalence and profile, and relationships with the disease clinical and laboratory indices, remain unclear. The present study investigated, in a large sample of patients recovered from COVID-19, the frequency of CI with both a face-to-face screening tool and comprehensive test battery (MCCB). The study also evaluated the profile of CI and its relationships with COVID-19 clinical and laboratory indices and with psychopathological features. Out of 1344 subjects assessed for eligibility, 736 completed the screening phase 11 months after the COVID-19 infection; 402 participated in the baseline phase and completed an in depth cognitive, clinical and laboratory assessment about one month later. More than one third of the screened subjects presented a CI (COG+); it was associated to age, education, male gender, COVID-19 severity, and presence of anosmia, dyspnea at rest and exertional dyspnea during the acute phase. COG+ subjects showed a higher severity of depression, anxiety and post-traumatic distress, and worse global functioning, than subjects without CI. The MCCB showed that 45% of the subjects had a CI involving attention, working memory, verbal learning, visual learning, and reasoning and problem solving. Finally, neurocognitive functioning was inversely correlated with LDH blood levels, a potential biomarker of disease severity. According to our findings, cognitive functioning should be routinely and periodically assessed in COVID-19 patients, especially in older subjects, who experienced more severe COVID-19 symptoms. In case of persisting dysfunctions cognitive training programs should be considered as treatment strategies.

Mechanisms of multi-omics and network pharmacology to explain traditional chinese medicine for vascular cognitive impairment: A narrative review.

BACKGROUND: The term "vascular cognitive impairment" (VCI) describes various cognitive conditions that include vascular elements. It increases the risk of morbidity and mortality in the elderly population and is the most common cognitive impairment associated with cerebrovascular disease. Understanding the etiology of VCI may aid in identifying approaches to target its possible therapy for the condition. Treatment of VCI has focused on vascular risk factors. There are no authorized conventional therapies available right now. The medications used to treat VCI are solely approved for symptomatic relief and are not intended to prevent or slow the development of VCI. PURPOSE: The function of Chinese medicine in treating VCI has not yet been thoroughly examined. This review evaluates the preclinical and limited clinical evidence to comprehend the "multi-component, multi-target, multi-pathway" mechanism of Traditional Chinese medicine (TCM). It investigates the various multi-omics approaches in the search for the pathological mechanisms of VCI, as well as the new research strategies, in the hopes of supplying supportive evidence for the clinical treatment of VCI. METHODS: This review used the Preferred Reporting Items for Preferred reporting items for systematic reviews and meta-analyses (PRISMA) statements. Using integrated bioinformatics and network pharmacology approaches, a thorough evaluation and analysis of 25 preclinical studies published up to July 1, 2023, were conducted to shed light on the mechanisms of TCM for vascular cognitive impairment. The studies for the systematic review were located using the following databases: PubMed, Web of Science, Scopus, Cochrane, and ScienceDirect. RESULTS: We discovered that the multi-omics analysis approach would hasten the discovery of the role of TCM in the treatment of VCI. It will explore components, compounds, targets, and pathways, slowing the progression of VCI from the perspective of inhibiting oxidative stress, stifling neuroinflammation, increasing cerebral blood flow, and inhibiting iron deposition by a variety of molecular mechanisms, which have significant implications for the treatment of VCI. CONCLUSION: TCM is a valuable tool for developing dementia therapies, and further research is needed to determine how TCM components may affect the operation of the neurovascular unit. There are still some limitations, although several research have offered invaluable resources for searching for possible anti-dementia medicines and treatments. To gain new insights into the molecular mechanisms that precisely modulate the key molecules at different levels during pharmacological interventions-a prerequisite for comprehending the mechanism of action and determining the potential therapeutic value of the drugs-further research should employ more standardized experimental methods as well as more sophisticated science and technology. Given the results of this review, we advocate integrating chemical and biological component analysis approaches in future research on VCI to provide a more full and objective assessment of the standard of TCM. With the help of bioinformatics, a multi-omics analysis approach will hasten the discovery of the role of TCM in the treatment of VCI, which has significant implications for the treatment of VCI.