Correction Of Cognitive Impairment Research Articles

Choline alfoscerate in the correction of cognitive impairment

In preclinical and clinical studies, choline alfoscerate (CA) has proven to be highly effective in the correction of cognitive impairment (CI). The clinical effect of CA is seen in the improvement of mental activity, concentration, ability to remember and recall information, cognitive and behavioural responses, elimination of emotional instability and apathy. Experimental studies have shown the effectiveness of CA in preventing atrophic changes in the cerebral cortex. Based on several studies conducted on the use of CA in the treatment of CI, it can be concluded that oral administration of CA at a dose of 600 mg/day can be recommended both as monotherapy and as part of complex therapy in patients with cerebrovascular diseases such as chronic cerebral ischemia. As part of complex therapy for CI in Alzheimer's disease, a combination of CA at a dose of 1200 mg/day with donepezil at a dose of 10 mg/day may be recommended. Several studies have demonstrated the efficacy of CA in the treatment of post-COVID and post-traumatic CI. The efficacy of CA administration in the treatment of CI (including vascular dementia) following ischemic stroke and transient ischemic attacks has been demonstrated. When CA is taken, there is also a reduction in anxiety and depressive disorders, asthenia, the severity of pain symptoms and changes in coordination. The duration of therapy should be 60 to 90 days, depending on the severity of CI, followed by an observation phase of up to 2 years. For successful treatment with CA, it is necessary to carry out repeated courses of CI treatment. Today, a new drug Cerpechol (600 mg/7 ml) has appeared on the Russian market, which has all the effects of CA. The convenience of the new form (oral solution) makes it possible to use it in patients with swallowing disorders.

Prospects for the use of intranasally administered insulin and insulin-like growth factor-1 in cerebral ischemia

Currently, the approaches used to treat stroke have significant limitations, and neuroprotective therapy is ineffective. In this regard, the search for effective neuroprotectors and the development of new neuroprotective strategies in cerebral ischemia are still relevant. Insulin and insulin-like growth factor-1 (IGF-1) play a key role in the functioning of the brain, are involved in the regulation of growth, differentiation and survival of neurons, neuronal plasticity, food intake, control peripheral metabolism and endocrine functions. They have a complex effect on the brain, including neuroprotective effects in cerebral ischemia and stroke. Experiments on animals and cell cultures have shown that insulin and IGF-1 under hypoxic conditions improve energy metabolism in neurons and glial cells, have a positive effect on blood microcirculation in the brain, restore nerve cell functions and neurotransmission processes, and have anti-inflammatory and antiapoptotic effects on brain cells. Of greatest interest to the clinic is the intranasal route of administration of insulin and IGF-1, since it allows dosed delivery of these hormones directly to the brain, bypassing the blood-brain barrier. Intranasally administered insulin demonstrates a pronounced positive effect in the correction of cognitive impairment in elderly people with neurodegenerative and metabolic disorders. Insulin and IGF-1 administered intranasally improve increase the survival of animals with ischemic stroke. The review discusses literature data and the results of our own studies on the mechanisms of the neuroprotective action of intranasally administered insulin and IGF-1 in cerebral ischemia and the prospects for their use to normalize CNS functions and reduce neurodegenerative changes in this pathology.

Dynamic electric neurostimulation in the cognitive rehabilitation of patients in the early recovery period of ischemic stroke

BACKGROUND: Post-stroke cognitive impairments negatively affect the results of rehabilitation, worsening the outcomes of motor functions recovery, daily activity, and also increase the likelihood of recurrent stroke and premature death. Therapeutic physical factors contribute to the activation of the body's reserve capabilities and aim at correcting metabolic and vascular disorders, improving the functional status of the nervous system, which allows them to be used in a complex of rehabilitation measures.
 AIM: to substantiate the use of dynamic electric neurostimulation in the correction of cognitive impairment in patients in the early recovery period of ischemic stroke.
 MATERIALS AND METHODS: A prospective cohort study of 60 patients in the early recovery period of ischemic stroke, with mild and moderate cognitive impairment, at an average age of 62.44.5 years, divided by random sampling into 3 groups: group 1 (n=25), in addition to the basic rehabilitation complex, which included medication, sessions with a neuropsychologist, massage and physical exercise therapy, received a 15-day course of dynamic electric neurostimulation from the "Neurodance-PCM" device; group 2 (n=20) received the basic rehabilitation complex and procedures from the placebo device similar to procedures on "Neurodance-PCM"; group 3 (n=15) received only the basic rehabilitation treatment. All patients underwent an assessment of cognitive status using the Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB) and the study of psychophysiological status on the psycho-physiological tester "NS-Psychotest", using the following tests: tapping test, the SchultePlatonov tables with red-black cells, test of simple visual-motor reaction, reaction to a moving object test.
 RESULTS: Over the two-week rehabilitation, it was found that the inclusion of dynamic electrical stimulation, in addition to the standard therapy of cognitive impairment in patients in the early recovery period of ischemic stroke, improves attention, memory, speech fluency, generalization functions, complicated choice reaction, increases the functions of visual attention and the speed of sensorimotor response, which was not noted in the comparison groups.
 CONCLUSIONS: The inclusion of dynamic electric neurostimulation in the rehabilitation complex of patients in the early recovery period of ischemic stroke with mild and moderate cognitive impairment may affect cognitive functions by stimulating the third block of the brain according to A.R. Luria and improving the neurodynamic support of higher mental functions.

P05-03 The role of physical training in the correction of cognitive impairment in patients with type 2 diabetes

BackgroundThe purpose of the study was to evaluate the role of physical exercises in improving cognitive functions in type 2 diabetes mellitus.MethodsThe study protocol was approved by an ethics committee and all patients signed an informed consent. We examined 204 patients with type 2 diabetes aged 61.7 ± 11.2 years (persons hospitalized in the endocrinology department of the clinics of the Siberian State Medical University, Tomsk). Blind double method patients were randomized into 2 groups: the main one was engaged in physical therapy and the control group (observation). The study was carried out in two stages: at the first visit, a clinical and psychological examination was conducted, which included the Montreal Cognitive Function Assessment Scale and the Diabetes-dependent Quality of Life Questionnaire; repeated clinical and psychological examination was carried out after rehabilitation after 6 monthsResultsAt the first stage the study revealed the presence of cognitive impairment in type 2 diabetes, mainly in tasks on visual-constructive skills, memory, attention and speech. These disorders were reduced after physical therapy (second stage) by 2.6 points (t = 0.01, p = 0.00006): visual-constructive skills (t = 0.0, p = 0.008), speech (t = 0.0, p = 0.005), abstraction (t = 0.0, p = 0.002) and memory (t = 0.0, p = 0.0007), no change in cognitive function occurred in the observation group. In terms of carbohydrate metabolism: the level of HbA1c decreased by 0.9%, fasting glycemia - by 1.6 mmol/L in main group, but increased by 0,1% of HbA1c and by 0,2 mmol/L of glycemia in the observation group (second stage) (t = 2.0, p = 0.000003; t = 3.0, p = 0.0008). Patients involved in physical therapy showed improvement in a larger number of parameters - leisure, travel, vacation, personal life, appearance, self-confidence, future confidence, financial situation, dependence, food choice, choice of drinks, total point (p > 0.05), when there was a decrease in points in the parameters of the control group.ConclusionDuring rehabilitation in patients with type 2 diabetes, there is an improvement in cognitive functions, carbohydrate metabolism and quality of life.

Polyfactorial approach in the correction of cognitive impairment in patients with post-Covid syndrome

The article discusses a multi-level polyfactorial approach in the correction of cognitive impairment in patients with post-Covid syndrome based on the combined use of cognitive-motivational correction of the psychological state and physiotherapeutic methods of treatment: multi-level magnetolaser therapy, advanced blood irradiation, transcranial neuroacoustic and light-pulse stimulation.
 According to the results of the analysis of the results of testing patients based on the Montreal scale for assessing cognitive functions before the start, after 6 and 12 procedures, as well as 4 weeks after the completion of rehabilitation in the first group, the average indicators of the level of cognitive functions changed from 18.2 to 21.4 points, in the second group from 17 to 26 points.
 Psychological testing using the psychometric tables of A. Beck and Spielberger-Hanin showed a decrease in the average level of depression after the procedures in the first group by 5.4±1.4 (from 27.5 to 22.1) points, the anxiety level by 4.9±0.3 (from 35.1 to 30.2), in the second group by 9.9±1.2 (from 27.3 to 17.4) and 8.2±0.4 (from 35.2 to 27.0), respectively. Additionally, it should be noted that the clients of the second group were more interested in conducting a second course.
 A multi-level approach in the medical rehabilitation of patients with post-Covid syndrome based on the use of psychological correction, magnetolaser effect on the projection of the liver, supravenous irradiation of blood and combined transcranial neuroacoustic and light-pulse stimulation in combination with endonasal breathing of a singlet-oxygen mixture in a magnetic field turned out to be the most effective for restoring cognitive functions.

Морфоліній 3-метил-1,2,4-тріазолін-5 тіоацетат у комплексній корекції когнітивних порушень у хворих на гострий інфаркт міокарда

Вивчено вплив морфоліній 3-метил-1,2,4-тріазолін-5 тіоацетату в корекції когнітивних порушень у хворих на гострий інфаркт міокарда (ГІМ). У дослідження було включено 70 пацієнтів із ГІМ і когнітивною дисфункцією до 60 років. Додатково вивчалися рівні С-реактивного білка і кортизолу крові, когнітивні порушення виявлялися тестами на когнітивну дисфункцію. Залежно від вигляду терапії хворі були поділені на 2 групи: 1-ша група (n = 35) — пацієнти зі стандартною схемою лікування при ГІМ; 2-га група (n = 35) — до стандартної терапії був доданий морфоліній 3-метил-1,2,4-тріазолін-5 тіоацетат. У результаті дослідження встановлено, що доданий до стандартної схеми лікування морфоліній 3-метил-1,2,4-тріазолін-5 тіоацетат сприяв значному зниженню когнітивної дисфункції в досліджуваних, тоді як у пацієнтів, які одержували стандартну терапію, регресування когнітивних порушень було значно зниженим.

Медотилін у лікуванні постінсультних когнітивних порушень

Стаття присвячена питанням лікування пацієнтів, які перенесли інсульт. Робиться акцент на корекції когнітивних порушень. Наведено дані дослідження впливу генеричного препарату Медотилін (холіну альфосцерат) на стан когнітивних функцій, показники повсякденної життєвої активності у хворих у відновному періоді ішемічного інсульту.

Low - intensity electrical impulse therapy in the correction of cognitive impairment in patients after ischemic stroke

Low - intensity electrical impulse therapy in the correction of cognitive impairment in patients after ischemic stroke

Testosterone, Depression, and Cognitive Impairment in Men: an Attempt at Practical Analysis

Cognitive impairment (CI) accompanies the aging process and is manifested by difficulties with memorization, learning, concentration and decision-making, which greatly complicates the daily life of the suffering subject. In addition, medical care and social adaptation of these patients are costly and put a significant strain on the health care system. According to a forecast by G. Corona’s group, the number of people with CIs will increase significantly in the coming years, reaching 131.5 million by 2030. To date, a significant amount of researches has been conducted to uncover the mechanisms of development and risk factors of CI in order to develop effective prevention and treatment programs. Age-related decline in testosterone levels are among the potentially modified risk factors of СI. The objective: to analyze the role of testosterone in pathogenesis of cognitive impairment and depression and the possibilities of testosterone therapy to correct them. Materials and methods. Evidence was collected from the study publications and meta-analyzes exploring the role of testosterone in pathogenesis, prevention and correction of cognitive impairment and depression over the past five years and preliminary analysis of data from our own study involving 547 men with hormonal disorders. Results. Cerebral vessels are the target for the direct (via androgen receptors) and indirect (via influence on cardiovascular risk factors) action of androgens. The testosterone insufficiency is associated with both metabolic and cardiovascular disorders (hypertension, diabetes, hyperlipidemia, obesity), as well as depression and CI. Serum-free-testosterone and free testosterone index are the most sensitive biomarkers of testosterone insufficiency in patients with depression and CI. The corrective effect of testosterone therapy (TT) on depression and CI depends on their severity and levels of androgens: a clinically and statistically significant effect was registered in mild disorders with androgen deficiency. The findings of the meta-analysis do not support the use of TT for improving attention, memory (working, verbal, visual), executive function, speech, visual-motor and visual-spatial abilities in subjects with eugonadism and hypogonadism. According to preliminary analysis of the results of our study, the nature of psycho-emotional disorders is determined by the sexual constitution (SC): weak type of SC (feminine men) is associated with the higher incidence of anxiety, the strong type of SC – with propensity for depression, the middle type of SC – with aggression. Thus, testosterone, estrogens, vasopressin, and adrenaline levels should be measured in patient with aggression. Conclusions. Despite the importance of androgens for mood and cognitive functions, and their synchronous decline during the aging process, the place of TT in the prevention/ correction of whole spectrum of CIs is still unclear. It is obvious now that TT can be justified in patients with mild disorders and proven androgen signal attenuation, but in most cases has no independent meaning. Further studies to find optimal TT indications and regimes are mandatory.

Эффективность антигипертензивной терапии в коррекции когнитивных нарушений у пациентов с гипертонической болезнью

Данные о способности антигипертензивной терапии снижать риск развития новых случаев когнитивных нарушений (КН) противоречивы. Поэтому целью исследования было оценить влияние антигипертензивной терапии на динамику когнитивных функций у пациентов с гипертонической болезнью (ГБ). В исследование включено 90 пациентов с ГБ I–II стадии, 2–3-й степени (средний возраст пациентов составил 49,66 ± 8,74 года). Всем пациентам проведены клинико-анамнестические обследования, использованы лабораторные и инструментальные методы исследования. Для изучения когнитивных функций применялись нейропсихологические тесты: GPCOG, MMSE, таблицы Шульте. Среди обследованных КП обнаружены у 36 пациентов (40 %). Для лечения в качестве антигипертензивной терапии была использована комбинация ингибитора ангиотензинпревращающего фермента или блокатора рецепторов ангиотензина + блокатор кальциевых каналов. На фоне антигипертензивной терапии отмечалось не только снижение и нормализация артериального давления, но и улучшение когнитивных функций. В частности, в 61,29 % случаев пациенты набрали достоверно больше баллов при повторном тестировании MMSE (p = 0,003) и GPCOG (p = 0,01), почти все пациенты (96,77 %) затратили достоверно меньше времени на выполнение заданий по таблицам Шульте (p = 0,0001). Общая сумма баллов по шкале MMSE выросла на 3,66 % (p = 0,003), суммарный балл по шкале GPCOG увеличился на 22,24 % (p = 0,01), а при контрольном выполнении теста Шульте пациенты потратили на 14,39 % меньше времени по сравнению с исходными результатами (p = 0,0001).

Priorities of medical rehabilitation of patients with recent experience of transient ischemic attack

Introduction.Transient ischemic attacks can be a predictor of a more severe cardiovascular event, the risk of which depends on many factors that requires a personalized approach. Neuropsychological disorders (cognitive, emotional) have a significant impact on quality of life and social activity and are often underestimated in patients with TIA. Comprehensive medical rehabilitation with the inclusion of antithrombotic therapy and psychocorrection measures may reduce the risk of recurrent cardiovascular events in patients with TIA.Purpose of the study: to substantiate the efficiency of complex medical and non-pharmacological rehabilitation in patients who underwent TIA by analyzing the characteristics of the main and leading concomitant diseases.Materials and methods. The morbidity of 351 TIA patients was studied and analyzed. The average age of the examined patients was 58.6 ± 2.2 years, there were 64.9% of women and 35.1% of men. All patients received an individualized medical rehabilitation program for 12 months with correction of identified neuropsychological disorders. Depending on background and concomitant diseases the antiplatelet or anticoagulants therapy was differently administrated.Results and dicussion. Psychological, cognitive, and physical disorders (based on subjective complaints) are common in patients with TIA. The prevalence of mental disorders in patients with TIA was 138.2 cases per 100 patients. The correction of cognitive impairment, depressive symptoms is associated with improved quality of life (p < 0.05). Repeated acute cerebrovascular events (TIA, ischemic stroke) were recorded during the first 6 months after TIA in 29 patients (10.4%) with severe stenosis of the brachiocephalic arteries, severe arterial hypertension and paroxysmal atrial fibrillation.Conclusion.The importance of comprehensive medical and social rehabilitation of patients with TIA is determined. The participation of a psychotherapist as a member of a multidisciplinary team is necessary. A significant role of the secondary prevention of acute cerebrovascular events is assigned to rational antithrombotic therapy.

Features of Cognitive Impairments in Patients with Comorbid Recurrent Affective and Panic Disorders

Objectives. To identify targets for medication and psychotherapy in the treatment of patients with comorbid recurrent affective and panic disorders based on results from studies of cognitive functions. Materials and methods. A set of pathopsychological methods (Schulte tables, correction test, 120-word test, cube drawing test, Binet and Berstein tests) was used. Cognitive status was studied in 60 patients with signs of recurrent affective (depressive) and panic disorders. ICD-10 diagnoses for the 27 patients making up the study group (SG) were recurrent affective disorder with mild and moderate depressive episodes (RAD, F33.0, F33.1) in combination with panic disorder (PD, F41.0). The control group (CG) included 33 patients with recurrent affective disorder (RAR, F33.0, F33.1) without panic disorder. Results and conclusions. All patients showed changes in the cognitive domain. Cognitive disorders in patients of the SG were more severe than those in patients of the CG. Cognitive functions in SG patients were characterized by being “left-hemisphere” impairments, in the form of paroxysmal emotional disorders with a predominance of fear and anxiety and dysfunction in the operation of a number of neuropsychological factors: successiveness, spatiality, inertia-mobility, for which the mediobasal and subcortical parts of the brain are responsible. Studies of cognitive impairments in remission provided evidence of some level of improvement in the cognitive domain in SG and CG patients, though there were no significant differences between the groups (p > 0.05). Targets for medication and psychotherapy in SG patients were attention, audioverbal memory, and components of thought (logical and spatial). The authors believe that use of neuropsychological correction of cognitive impairments is appropriate in patients of this group.

The result of prospective randomized study CITADEL - the efficacy and safety of drug cytoflavin in postcovid rehabilitation

To investigate the structure of postcovid syndrome, age and gender characteristics of its course, and to assess the effect of Cytoflavin on the clinical course of neurological disorders in patients who have undergone COVID-19. The study included 100 patients, the average age was 40.4±11.7 years, there were statistically more men than women. The duration of the transferred SARS-CoV-2 days is from 30 to 90 days from the date of recovery). By random sampling, the patients were divided into two groups, the main group, received Cytoflavin tablets, a course of 25 days, 2 tablets 2 times a day. Comparison group - other drugs (vitamins, nootropic drugs). All patients were examined on the day of treatment and 25-30 days after the end of therapy. The status was assessed using Asthenia Assessment Scale (MFI-20), Brief Mental Status Assessment Scale (MMSE), Quality-of-Life Questionnaire (EQ-5D), General Health Assessment Scale, and Pittsburgh Sleep Quality Index (PSQI). The analysis of laboratory parameters was carried out retrospectively. Postcovid syndrome was more common in men, among comorbid conditions arterial hypertension and atherosclerosis prevailed, neurocognitive and autonomic disorders predominated. Appointment of Cytoflavin made it possible to achieve a pronounced anti-asthenic effect with the correction of cognitive impairments, which was reflected in a significantly more significant positive dynamics of indicators of all scales. An additional effect of Cytoflavin was revealed - a decrease in the severity of thrombocytopenia. During the observation period, no patient had any serious adverse events or side effects associated with taking the drug. Prescription of the drug does not require age-related dose adjustment and is well combined with basic therapy for concomitant pathology.

Preliminary results of rehabilitation intervention for the correction of cognitive impairment in patients with multiple sclerosis

One of the leading symptoms in patients with multiple sclerosis (MS) is cognitive impairment. It often affects aspects of cognition such as learning ability, memory, processing speed, and attention. It has been proven that patients often complain of difficulties in multitasking and choosing the right words. These problems are often underestimated. Various studies show that regular physical activity, mainly aerobic exercise, can potentially improve cognitive function. Positive effects on concentration, memory, and multitasking were described. In March 2019, the Tyumen regional center of MS, together with the clinical Institute of the brain (Yekaterinburg), launched a clinical study of methods for rehabilitation of cognitive disorders in patients with MS. There was a statistically significant improvement in MOCA-test scores, according to SDMT and PASSAT data in the main group of MS patients. Despite a significant improvement in cognitive function, the self-assessment of mental function according to the MSQOL54-MN test in this group of patients did not change. Our preliminary results suggest that a comprehensive and well-controlled training program can improve cognitive abilities in MS patients even after a short course of treatment.

Prospects Of Using Resveratrol For Cognitive Impairment Correction In Patients With Type II Diabetes Mellitus

Our goal was to study the effectiveness of resveratrol in correcting cognitive impairments and in normalization of neurotrophin levels in patients with type II diabetes mellitus. Material and Methods ― In a randomized placebo-controlled trial, 100 patients with a verified diagnosis of type II diabetes mellitus took part, who were subsequently placed into two groups: the treatment group of 50 patients taking a polyphenol therapeutic drug in addition to standard therapy, and the comparison group of 50 indivuduals taking a placebo medication in addition to standard therapy. The control group consisted of 30 individuals belonging to the health group I sensu RF Ministry of Healthcare. Treatment efficacy was assessed using the Montreal Cognitive Assessment (MoCA) scale. The concentrations of insulin-like growth factor 1 (IFR-1), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) in blood plasma were analyzed before and after treatment completion (10 weeks later). Results ― Before starting treatment, patients exhibited an increase in the level of IFR-1 and a decrease in the content of neurotrophic factors (BDNF and NGF) in their blood plasma. In patients receiving resveratrol in addition to standard treatment, changes in IFR-1, BDNF and NGF in blood plasma were more noticeable relative to the comparison group and approached the values of the control group. According to the MoCA scale, more pronounced dynamics of cognitive functions was observed in patients of the treatment group. Conclusion ― The high efficiency of the polyphenol therapeutic drug resveratrol in the correction of cognitive impairments in patients with type II diabetes mellitus was established. The use of resveratrol promoted the normalization of the levels of IFR-1 and neurotrophic factors in the blood plasma: in the treatment group, a more pronounced statistically significant decrease in the concentration of IFR-1, along with an increase in BDNF and NGF levels, were observed relative to the control group. The clinically significant effect of resveratrol was in the reduction of cognitive deficit symptoms, which was confirmed by the data of dynamic monitoring on the MoCA scale: in treatment group, there was a statistically significant improvements of optical and spatial functions, attention, abstract thinking, and fulfilling delayed reproduction task; in the comparison group, there was a statistically significant improvement solely of completing delayed reproduction task.

Contemporary approaches to correction of cognitive impairment in endogenous depression

Cognitive dysfunction is one of the basic symptoms of endogenous depression, gaining much of the researchers’ interest lately. It is observed at the initial stage, at the peak intensity of depressive symptoms and even after their reduction, which leads to the persistence of residual depressive state. Cognitive impairment during the depressive episode can be detected by objective methods (clinical and neuropsychological), and their subjective importance is being revealed by standardized questionnaires. Depressed patients show lower results in executive functions, working memory, reaction speed, verbal learning, immediate and delayed recall subtests of neuropsychological batteries. There are few pharmacological agents (mostly antidepressants) with well-proven procognitive activity in depression. Besides, some new pharmacological and non-pharmacological approaches for treatment of cognitive impairment in depression have appeared lately and are described in literature as promising.

An enriched environment improves cognitive impairment in an Alzheimer’s disease model by enhancing the secretion of exosomal miR‐146a from the choroid plexus

AbstractBackgroundAn enriched environment (EE) is reported to prevent the cognitive impairment and ameliorate the pathologic changes in mouse models of Alzheimer's disease (AD), however the mechanisms have not been fully clarified. In this study, we examined whether an EE enhance the secretion of exosomal miRNA(miR)‐146a from the choroid plexus (CP) and ameliorate the pathologic changes in AD model.MethodMale 5×FAD mice (B6.Cg‐Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax) which develop Aβ plaques in the brain and exhibit cognitive decline were used. At 3 months of age, these mice were divided into control cage (CC) or EE, then housed in either cage until 6 months old. Then, cognitive function was evaluated using Morris Water Maze (MWM) test and mice were sacrificed. In vitro experiments, the secretion of exosomal miR‐146a from CP epithelial cells were evaluated after stimulating of interferon (IFN)‐γ. In addition, we cultured hippocampal astrocytes and added 1 µM Aβ fibrils and 250 ng/ml lipopolysaccharide (LPS) to them to mimic the pathological change of astrocytes in AD. Then we transfected miR‐146a into Aβ/LPS induced inflammatory astrocytes to evaluate the effect of miR‐146aResultIn MWM test, the cognitive impairment in 5×FAD mice was completely prevented by EE. In morphological study, EE ameliorated the expression of TNFα in astrocytes and increased the intensity of synaptophysin in the subiculum area of the hippocampus. In AD model mice treated with EE, increased levels of micro RNA (miR)‐146a and down‐regulation of NF‐κB were observed in the hippocampus. In addition, increased levels of IFN‐γ were seen in serum from mice exposed to an EE. In vitro, enhanced miR‐146a expression was observed in exosomes derived from the CP after IFN‐γ treatment. In further in vitro experiments, miR‐146a transfection ameliorated Aβ/LPS induced astrocytic inflammation by down‐regulating tumor necrosis factor receptor‐associated factor 6 and NF‐κB.ConclusionThe secretion of exosomal miR‐146a from CP, that is enhanced by EE, is a key factor in ameliorating astrocytic inflammation, leading to synaptogenesis and correction of cognitive impairment.

An enriched environment prevents cognitive impairment in an Alzheimer’s disease model by enhancing the secretion of exosomal microRNA-146a from the choroid plexus

Alzheimer’s disease (AD) is characterized by the extensive deposition of amyloid-β plaques and neurofibrillary tangles. We previously found that preserved function of astrocytes is associated with cognitively normal subjects with AD pathology. Here we show that an enriched environment (EE) can prevent cognitive impairment in AD model mice by ameliorating astrocytic inflammation and increasing synaptic density in the subiculum area of the hippocampus. In AD model mice treated with an EE, increased levels of microRNA (miR)-146a and down-regulation of NF-κB were observed in the hippocampus. In addition, increased levels of interferon (IFN)-γ were seen in serum from mice exposed to an EE. In vitro, enhanced miR-146a expression was observed in exosomes derived from the choroid plexus (CP) after IFN-γ treatment. In further in vitro experiments, we transfected miR-146a into Aβ/lipopolysaccharide-induced inflammatory astrocytes and showed that miR-146a ameliorated astrocytic inflammation by down-regulating tumor necrosis factor receptor-associated factor 6 and NF-κB. The present study indicates that following an EE, exosomal miR-146a derived from the CP cells is a key factor in ameliorating astrocytic inflammation, leading to synaptogenesis and correction of cognitive impairment.

Bone marrow-derived mesenchymal stem cells improve cognitive impairment in an Alzheimer\u2019s disease model by increasing the expression of microRNA-146a in hippocampus

Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β and tau. We previously reported that administration of bone marrow mesenchymal stem cells (BM-MSCs) ameliorates diabetes-induced cognitive impairment by transferring exosomes derived from these cells into astrocytes. Here, we show that intracerebroventricularly injected BM-MSCs improve cognitive impairment in AD model mice by ameliorating astrocytic inflammation as well as synaptogenesis. Although AD model mice showed an increase in NF-κB in the hippocampus, BM-MSC-treated AD model mice did not show this increase but showed an increase in levels of microRNA (miR)-146a in the hippocampus. Intracerebroventricularly injected BM-MSCs were attached to the choroid plexus in the lateral ventricle, and thus, BM-MSCs may secrete exosomes into the cerebrospinal fluid. In vitro experiments showed that exosomal miR-146a secreted from BM-MSCs was taken up into astrocytes, and an increased level of miR-146a and a decreased level of NF-κB were observed in astrocytes. Astrocytes are key cells for the formation of synapses, and thus, restoration of astrocytic function may have led to synaptogenesis and correction of cognitive impairment. The present study indicates that exosomal transfer of miR-146a is involved in the correction of cognitive impairment in AD model mice.

Possibilities of antihypertensive therapy in correction of cognitive impairment in hypertensive patients

Possibilities of antihypertensive therapy in correction of cognitive impairment in hypertensive patients