Treatment Of Cognitive Disorders Research Articles

Role of Crataegus oxyacantha (Hawthorn) on scopolamine induced memory deficit and monoamine mediated behaviour in rats

Treatment of cognitive disorders is a challenging task in neurology since long time. Crataegus oxyacantha, also known as hawthorn belongs to family Rosaceae grown in colder areas and is one of the most widely used herb for the treatment of heart disorders. Traditionally Crataegus oxyacantha has also been used to treat Alzheimer disease, nervousness, stress, pain, and sleep disorders. In this study nootropic activity of petroleum ether, chloroform and methanol extract of Crataegus oxyacantha leaves was assessed using elevated plus maze model. Scopolamine (1 mg/kg) was used as amnesia inducing agent and piracetam (120 mg/kg) as standard nootropic drug. On the last day of the experiment, biochemical parameters like acetylcholinesterase, lipid peroxidase and superoxide dismutase were measured in brain homogenate. Effect of Crataegus oxyacantha on monoamines mediated behaviour was assessed through lithium induced head twitches and haloperidol induced catalepsy model in rats. Among all three extracts, methanol extract of Crataegus oxyacantha caused highest reduction in transfer latency time significantly as measured on 7th and 14th day and on 8th and 15th day on elevated maze and also decreased acetylcholinesterase and lipid peroxidase level and increased super oxide dismutase content as compared to scopolamine group. Methanol extract of Crataegus oxyacantha (200 mg/kg and 400 mg/kg) decreased number of head twitches and duration of catalepsy in rats significantly compared to vehicle treated group. So our study showed promising effect of Crataegus oxyacantha in enhancing learning and memory due to the presence of certain phytoconstituents.

The sodium channel activator Lu AE98134 normalizes the altered firing properties of fast spiking interneurons in Dlx5/6+/- mice.

Mental disorders such as schizophrenia are associated with impaired firing properties of fast spiking inhibitory interneurons (FSINs) causing reduced task-evoked gamma-oscillation in prefrontal cortex. The voltage-gated sodium channel NaV1.1 is highly expressed in PV-positive interneurons, but only at low levels in principal cells. Positive modulators of Nav1.1 channels are for this reason considered potential candidates for the treatment of cognitive disorders. Here we examined the effect of the novel positive modulator of voltage-gated sodium channels Lu AE98134. We found that Lu AE98134 facilitated the sodium current mediated by NaV1.1 expressed in HEK cells by shifting its activation to more negative values, decreasing its inactivation kinetics and promoting a persistent inward current. In a slice preparation from the brain of adult mice, Lu AE98134 promoted the excitability of fast spiking interneurons by decreasing the threshold for action potentials. We then tested if Lu AE98134 could normalize the altered firing properties of FSINs in Dlx5/6+/- mutant mice. FSINs of this model for schizophrenia are characterized by broader action potentials and higher spike threshold. We found that in the presence of Lu AE98134, the firing frequency was increased while the spike duration and the threshold were decreased. Compounds with similar mode of action appear as promising candidates for restoring cognitive deficits present in schizophrenia.

Ameliorative Effects of Roots of <I>Asparagus adscendens</I> Roxb. on Cognitive Impairments and Brain Aging Induced by Scopolamine and Diazepam in Animal Models Relevant to Alzheimer's Disease

Memory loss in dementia is often the most disabling feature of many disorders, impairing the normal daily activities of the patients and profoundly affecting their families. Treatment of cognitive disorders like dementia and Alzheimer's disease has been challenging since no potential drug is available at present with proved efficacy. In the present study, nootropic activity of methanolic extract of roots of Asparagus adscendens Roxb.(AR) was studied in mice. Elevated plus maze and passive avoidance paradigm were employed to evaluate learning and memory. Scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) were used to induce amnesia in mice. AR (50 and 100 mg/kg, p.o.) significantly attenuated amnesic deficits induced by scopolamine, diazepam and natural aging. Furthermore, it also reversed aging induced amnesia due to natural aging of mice. AR profoundly increased whole brain acetyl cholinesterase inhibition activity. Hence, AR might prove to be a useful memory restorative agent in the treatment of dementia seen in the elderly. The underlying mechanism of its action may be attributed to its antioxidant and acetyl cholinesterase inhibition properties.

Sargassum swartzii extracts ameliorate memory functions by neurochemical modulation in a rat model.

Recently, considerable attention has been paid to drug exploration from natural sources for treating memory loss, a major manifestation of various neurodegenerative diseases. Increasing evidences implicate brain serotonin metabolism in learning and memory, supporting the notion that targeting 5-HT (5-hydroxytryptamine) and its receptors would be beneficial in the treatment of cognitive disorders. In the present study, behavioral and neurochemical effects were examined following administration of Sargassum swartzii extracts in albino Wistar rats. Increase in spatial working memory and recognition memory was exhibited by the seaweed-treated rats as compared to controls. Plasma tryptophan, brain 5-HT, and 5-hydroxyindoleacetic acid levels were measured using HPLC-ECD, and a significant increase in brain 5-HT metabolism was observed in the seaweed-treated rats. The increase in memory functions following repeated administration of S. swartzii extracts is suggested to be due to the increased serotonergic neurotransmission in the brain of seaweed-treated rats.

Heroin-piracetam mixture: Suggested mechanisms of action and risks of misinterpretation for drug users.

Piracetam is a positive allosteric modulator of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor that has been frequently used in the treatment of cognitive disorders. Press and internet reports indicate that the use of piracetam, as a heroin adulterant, has spread rapidly in some countries, especially in Asia and Europe. Its use, as adulterant, is believed to produce more profound desirable effects, while decreasing hangover. Recent surveys demonstrated that piracetam protects neurons from heroin-induced apoptosis. The protective role of this adulterating substance may be related to restoration of beta-endorphin levels and to its neuroprotective effects. The aim of this paper is to review the relevant literature and suggest the main hypothetical mechanisms that justify its use as a heroin adulterant, try to understand if its use could help people who want to come off heroin by reducing withdrawal symptoms and, finally, give useful information that permit us to understand why drug trafficking organisations started to use piracetam as heroin adulterant.

The effectiveness of piribedil for the treatment of cognitive disorders in patients with coronary heart disease: results of six-month
 observation

Aim. The detection of cognitive deficiency after heart bypass surgery, the evaluation of the influence of piribedil on the higher cerebral function in the early postoperative period during the follow-up. Materials and methods. 64 patients with ischemic heart disease were examined. They were divided into two groups. Patients of the main group (n=32) were treated with pronoran (piribedil) at a daily dose of 50 mg for 3 months. 32 patients of the control group received standard therapy in the postoperative period. All patients had undergone heart bypass surgery. Cognitive functions were examined before operation, 10 days , three and six months after surgery. Results. Positive dynamics of all tested parameters was documented in the patients of the main group within 6 months after the onset of therapy. In control patients, cognitive disorders remained at the preoperative level based on the results of three tests. Conclusion. The positive results of piribedil therapy suggest that piribedil has positive effect on memory, attention and psychomotor activity of the patients

What do Cochrane systematic reviews say about non-pharmacological interventions for treating cognitive decline and dementia?

Dementia is a highly prevalent condition worldwide. Its chronic and progressive presentation has an impact on physical and psychosocial characteristics and on public healthcare. Our aim was to summarize evidence from Cochrane reviews on non-pharmacological treatments for cognitive disorders and dementia. Review of systematic reviews, conducted in the Discipline of Evidence-Based Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo. Cochrane reviews on non-pharmacological interventions for cognitive dysfunctions and/or type of dementia were included. For this, independent assessments were made by two authors. Twenty-four reviews were included. These showed that carbohydrate intake and validation therapy may be beneficial for cognitive disorders. For dementia, there is a potential benefit from physical activity programs, cognitive training, psychological treatments, aromatherapy, light therapy, cognitive rehabilitation, cognitive stimulation, hyperbaric oxygen therapy in association with donepezil, functional analysis, reminiscence therapy, transcutaneous electrical stimulation, structured decision-making on feeding options, case management approaches, interventions by non-specialist healthcare workers and specialized care units. No benefits were found in relation to enteral tube feeding, acupuncture, Snoezelen stimulation, respite care, palliative care team and interventions to prevent wandering behavior. Many non-pharmacological interventions for patients with cognitive impairment and dementia have been studied and potential benefits have been shown. However, the strength of evidence derived from these studies was considered low overall, due to the methodological limitations of the primary studies.

Synthesis and biological evaluation of novel N1-phenylsulphonyl indole derivatives as potent and selective 5-HT6R ligands for the treatment of cognitive disorders

A series of 1-[3-(4-methyl piperazin-1-ylmethyl) phenylsulfonyl]-1H-indole and 1-[3-(4-ethyl piperazin-1-ylmethyl) phenylsulfonyl]-1H-indole derivatives were designed and synthesized as 5-HT6 receptor (5-HT6R) ligands. The lead compound 1-[4-methyl-3-(4-methyl piperazin-1-yl methyl) phenylsulfonyl]-1H-indole dihydrochloride (6b), in this series, has shown potent in vitro binding affinity, selectivity, good pharmacokinetics (PK) profile and activity in the animal models of cognition.

Does genetic testing for ERα gene polymorphisms provide new possibilities of treatment for cognitive function disorders in postmenopausal women?

It is commonly considered that cognitive abilities decrease with age, especially with respect to processing and psychomotor speed. It is an interesting issue whether, apart from the ageing process, the undergoing of menopause itself deteriorates cognitive functions, compared to women at reproductive age. Hopes for improvement of cognitive functions were pinned on the use of menopausal hormone therapy. However, the results of studies concerning the effect of hormone replacement therapy on cognition proved to be contradictory. It seems that the essence of the problem is more complicated than only estrogen deficiency. It is suggested that estrogen receptor α (ERα) polymorphism may be responsible for the differences in the effect of estrogens on cognitive processes. The article presents current knowledge concerning the effect of estrogens on the central nervous system, especially the role of ERα polymorphism, with respect to foreseeing benefits from the use of exogenous estrogens for cognitive functions. At the present stage of research, ERα appears to be poorly specific; nevertheless, it may be an important instrument for the classification of peri- and post-menopausal patients in the group where therapy with the use of estrogens may bring about benefits in terms of prevention and treatment of cognitive disorders. It also seems necessary to conduct prophylactic, screening examination of cognitive functions in post-menopausal women, in order to identify those at risk of the development of dementia.

Curcumin and Resveratrol in the Management of Cognitive Disorders: What is the Clinical Evidence?

A growing body of in vitro and in vivo evidences shows a possible role of polyphenols in counteracting neurodegeneration: curcumin and resveratrol are attractive substances in this regard. In fact, epidemiological studies highlight a neuroprotective effect of turmeric (rhizome of Curcuma longa L.), the main source of curcumin. Moreover, the consumption of red wine, the main source of resveratrol, has been related to a lower risk of developing dementia. In this review, we analyzed the published clinical trials investigating curcumin and resveratrol in the prevention or treatment of cognitive disorders. The ongoing studies were also described, in order to give an overview of the current search on this topic. The results of published trials (five for curcumin, six for resveratrol) are disappointing and do not allow to draw conclusions about the therapeutic or neuroprotective potential of curcumin and resveratrol. These compounds, being capable of interfering with several processes implicated in the early stages of dementia, could be useful in preventing or in slowing down the pathology. To this aim, an early diagnosis using peripheral biomarkers becomes necessary. Furthermore, the potential preventive activity of curcumin and resveratrol should be evaluated in long-term exposure clinical trials, using preparations with high bioavailability and that are well standardized.

Role of Artemisia macrocephala as enzymes inhibitor in dementia and nociception! A pharmacological study

This study was conducted for investigating potentials of methanolic extract (Am. CME) and subsequent fractions of Artemisia macrocephala (A. macrocephala) for the inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and cyclo-oxygenase (COX-1 and COX-2). Ellman's assay was followed for the investigation of AChE and BChE inhibitory potentials of Am. CME and subsequent fractions of A. macrocephala while cyclo-oxygenase inhibition was investigated using a COX inhibition assay. For AChE inhibitory assay, chloroform (Am.CHF), ethyl acetate (Am.EtOAc) fractions and Am.CME showed 85.76 ± 1.49, 77.50 ± 0.86 and 71.00 ± 1.15 % inhibition of the enzyme respectively at 1000µg/mL concentration. Similarly, for BChE inhibition assay, Am.CHF, Am.EtOAc and Am. CME showed 82.56±0.68, 73.56 ± 1.56 and 68.55±0.81% inhibition of the enzyme respectively at 1000µg/mL concentration. Am.CHF and Am.CME were found to be most active against COX-1 and COX-2. Against COX-1, AmCHF and Am.CME showed 75.23 ± 0.98 and 73.33 ± 0.46% inhibition respectively at 1000µg/mL concentration. Similarly against COX-2, they showed 81.23 ± 1.23 and 79.40 ± 0.46% respectively at 1000µg/mL concentration. It can be concluded from results that Artemisia macrocephala can be used in the treatment of cognitive disorders, along with neurodegenerative ailments, various neuro-pharmacological ailments and certain painful conditions.

Cognitive Impairment in Multiple Sclerosis.

Multiple sclerosis (MS) is a socially significant immune-mediated disease, characterized by demyelination, axonal transection and oligodendropathy in the central nervous system. Inflammatory demyelination and neurodegeneration lead to brain atrophy and cognitive deficit in up to 75% of the patients. Cognitive dysfunctions impact significantly patients' quality of life, independently from the course and phase of the disease. The relationship between pathological brain findings and cognitive impairment is a subject of intensive research. Summarizing recent data about prevalence, clinical specificity and treatment of cognitive disorders in MS, this review aims to motivate the necessity of early diagnosis and complex therapeutic approach to these disturbances in order to reduce the social burden of the disease.

Obstacles and Opportunities for Cholinergic Drug Development in the Treatment of Cognitive Disorders.

The frequency of neuropsychiatric disorders is greater than that of cancer, cardiovascular disease, and diabetes combined, and is growing at a faster rate than any other ailments in the United States or Europe. Despite a considerable need for the development of treatments for central nervous system disorders, pharmaceutical companies continue to reduce investment in this area of research. Of particular concern is the treatment of diseases and disorders that affect cognitive function, which are often given a lower priority for research investment than life threatening conditions or those with overt physical symptoms. Several reasons exist for this reduced investment, including a poor understanding of the mechanisms underlying impaired cognitive function, costly and long periods of development for these medications, disproportionately lower success rates, and a stigma associated with the medical treatment of mental illness. This paper will discuss these issues, review some of the successes resulting from research investment and discuss opportunities that should encourage increased research investment in cognitive disorders and their treatment.

Dementia Competence Network. Results and outlook

The Dementia Competence Network (DCN) is represented by academic memory clinics and has three major aims: (1)To facilitate the development of diagnostic tools including neuropsychology, biomarkers, imaging and genetics. (2)To implement clinical trials in mild cognitive impairment and dementia and (3)to improve standard care for dementia in Germany. This article summarizes the achievements of the DCN so far and highlights future perspectives. The DCN has built up two multicentre cohorts. Within the first cohort, patients with mild cognitive impairment or mild dementia were examined longitudinally using multiple neuropsychological assessments and numerous different biomarkers. In asubgroup of the first cohort, patients were treated with antidementive drugs in two placebo-controlled clinical trials. The second cohort included cognitively healthy older people and examined repetitively clinical, neuropsychological and psychosocial parameters for ten years. The DCN has generated alarge data and biomaterial bank. Numerous publications have helped to develop further diagnostic procedures and treatment of cognitive disorders and dementia. The DCN has contributed to end stigmatisation of dementia.

Cognitive disorders in stroke patients: the possibilities of pharmacological correction

To determine the efficacy and safety of cellex in treatment of cognitive disorders in acute ischemic stroke (IS). The study involved 246 patients with acute IS. Patients were randomly divided into two groups depending on the use of cellex or placebo along with basic treatment during 10 days. The dynamics of neuropsychological status was evaluated. In IS patients, treatment with cellex have led to more rapid and marked reduction of mild and moderate cognitive disorders.

A synergistic effect of magnesium ions and lambertianic acid amide in the regulation of NMDA-type glutamate receptors in pyramidal neurons of the hippocampus

Although caused by different mechanisms, the most common neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, as well as multiple sclerosis, epilepsy, and ischemic brain damage, may share a common pathway: abnormalities of ionotropic glutamate receptors, particularly, of the NMDA type. Drugs with a glutamatergic mechanism of action are currently being intensively developed for the treatment of cognitive disorders and neurodegenerative processes. The goal of this work is to study the effect of lambertianic acid amide on glutamatergic synaptic transmission. A functional integration of glutamate and nonneurotransmitter receptors of hippocampal pyramidal neurons has been analyzed. The plasma membrane receptors are prevalently involved in integration of the effects of selective signaling molecules (mediators) and numerous internal and external factors, as well as the sharing of signaling pathways. An examination of mouse hippocampal slices has shown that lambertianic acid amide does not interfere with the development of NMDA receptor-dependent synaptic potentiation and displays neuroprotective properties, normalizing the epileptiform activity triggered by the absence of an endogenous ion channel blocker (magnesium ions) of the NMDA receptor. Lambertianic acid extracted from the Siberian pine (Pinus sibirica R. Mayr) needles and galipot and its derivatives are presumably a promising source of drugs with a glutamatergic mechanism of action that are suitable for the treatment of cognitive disorders and neurodegenerative diseases.

TORC2: a novel target for treating age-associated memory impairment.

Memory decline is one of the greatest health threats of the twenty-first century. Because of the widespread increase in life expectancy, 20 percent of the global population will be over 60 in 2050 and the problems caused by age-related memory loss will be dramatically aggravated. However, the molecular mechanisms underlying this inevitable process are not well understood. Here we show that the activity of the recently discovered mechanistic target of rapamycin (mTOR) complex 2 (mTORC2) declines with age in the brain of both fruit flies and rodents and that the loss of mTORC2-mediated actin polymerization contributes to age-associated memory loss. Intriguingly, treatment with a small molecule that activates mTORC2 (A-443654) reverses long-term memory (LTM) deficits in both aged mice and flies. In addition, we found that pharmacologically boosting either mTORC2 or actin polymerization enhances LTM. In contrast to the current approaches to enhance memory that have primarily targeted the regulation of gene expression (epigenetic, transcriptional, and translational), our data points to a novel, evolutionarily conserved mechanism for restoring memory that is dependent on structural plasticity. These insights into the molecular basis of age-related memory loss may hold promise for new treatments for cognitive disorders.

Waking up to the alarm: sleep, clocks, and making memory (s)tick.

Waking up to the alarm: sleep, clocks, and making memory (s)tick.

A review study on medicinal plants used in the treatment of learning and memory impairments

Alzheimer's disease (AD) is a progressive brain disorder that gradually impairs the person's memory and ability to learn, reasoning, judgment, communication and daily activities. AD is characterized clinically by cognitive impairment and pathologically by the deposition of β amyloid plaques and neurofibrillary tangles, and the degeneration of the cholinergic basal forebrain. During the progression of AD patients may produce changes in personality and behavior, such as anxiety, paranoia, confusion, hallucinations and also to experience delusions and fantasies. The first neurotransmitter defect discovered in AD involved acetylcholine as cholinergic function is required for short-term memory. Oxidative stress may underlie the progressive neurodegeneration characteristic of AD. Brain structures supporting memory are uniquely sensitive to oxidative stress due to their elevated demand for oxygen. The neurodegenerative process in AD may involve β amyloid toxicity. Neurotoxicity of β amyloid appears to involve oxidative stress. Currently, there is no cure for this disease but in new treatments, reveals a new horizon on the biology of this disease. This paper reviews the effects of a number of commonly used types of herbal medicines for the treatment of AD. The objective of this article was to review evidences from controlled studies in order to determine whether herbs can be useful in the treatment of cognitive disorders in the elderly.

DIAGNOSIS AND CORRECTION OF COGNITIVE DISORDERS IN CHILDREN WITH TRAUMATIC BRAIN INJURY SEQUELAE

научный биометрический журнал, который знакомит читателя с клиническими рекомендациями и особенностями применения лекарственных и вакцинных средств у детей, предоставляет исчерпывающую информацию о воздействии лекарственных средств на плод, о проводимых в