Correction of cognitive impairment in patients with cerebral vascular disorders

The principles of correction of cognitive impairment in patients with cerebral vascular disorders are considered. The effectiveness of the action of memantine hydrochloride on cognitive functions, daily activity, emotional and somatic state has been proved, and its appointment to patients with this pathology is recommended.

Key words: cerebral disorders, memantine hydrochloride.

Cognitive impairment (CN) is observed in 20-50% of patients who have suffered a stroke, and have a negative impact on social activity and quality of life of patients. A close correlation between the quality of life and the prognosis of the degree of disability of patients is proved.

According to epidemiological data, 4-6% of patients who have had a stroke develop dementia in the next six months. After 5 years, this indicator increases to 20-25%. Even more often, moderate cognitive impairment or mild dementia is detected.

By postinsultaneous cognitive impairment (PICN), any cognitive impairment that has a temporary connection with a stroke, that is, it is detected within the first 3 months after a stroke (early PIC), or at a later date, but usually not later than a year after the stroke PICN). A three-month interval was introduced in the criteria of vascular dementia NINDS-AIREN as one of the evidence of a causal relationship between cerebrovascular disease and dementia.

In 1993, V. Hachinski proposed the term "vascular cognitive disorders" (SCR) to denote violations of cognitive functions resulting from cerebrovascular disease. In the structure of TFR, it was suggested to consider vascular dementia proper, violation of cognitive functions due to a combination of vascular and neurodegenerative cerebral pathology (mixed dementia with the vascular component) and vascular cognitive disorders that do not reach the degree of dementia.

By the degree and extent of cognitive deficits, we can distinguish three variants of cognitive impairment that occur after a stroke:

• focal (monofunctional) cognitive impairment, usually associated with focal brain damage and involving only one cognitive function (aphasia, amnesia, apraxia, agnosia); in such cases, over time, one or another degree of compensation for cognitive deficits is possible due to the plasticity of the brain and conserved cognitive functions;
• multiple cognitive impairments that do not reach the degree of dementia (post-stroke moderate cognitive impairment);
• multiple cognitive impairments that cause impaired social adaptation (regardless of the available motor or other focal neurological deficit) and, accordingly, allow to diagnose dementia (post-stroke dementia).

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]

Symptoms of vascular cognitive disorders

The clinical picture of vascular cognitive disorders, reflecting the dysfunction of the frontal lobes of the brain due to the formation of the syndrome of separation of the cortex of the frontal lobes and subcortical ganglia, often involves slowed thinking, difficulty concentrating, disturbing voluntary attention and switching from one task to another, increased distraction, perseveration and increased impulsivity, reduction of speech activity, analytical abilities, planning, organization and control of activities.

Primary memory impairments (disruption of memorization of a new material, difficulty in remembering previously acquired information) are not characteristic of vascular cognitive disorders, but memory imbalances can be noted: it is difficult for patients to keep a large amount of information, to switch from the perception of one information to another. This makes it difficult to learn and gain new skills, but does not extend to memorizing and reproducing life events. In patients with arterial hypertension (AH), lower results are shown for all neuropsychological tests (reaction time, spatial, auditory and visual memory, immediate and delayed reproduction of memorized words, speed of response, information analysis, problem solving, identification of similarities and differences, generalization, activity, motivation, program construction, inference, voluntary attention).

The morphological basis for the development of cognitive impairment can be:

• stroke in the strategic areas of the brain that provide memory and other critical mental functions, if they are damaged, a significant cognitive defect arises;
• multiple vascular lesions (lacunas), when extensive brain damage leads to a rupture of the connections between the frontal cortex and other important centers, which causes cognitive deficits;
• leukoareoz - rarefaction of white matter, which is the cause of cognitive disorders in patients with AH, with the formation of discirculatory encephalopathy.

Vascular lesion of the brain is accompanied by a violation of the functioning of neurotransmitter systems involved in the regulation of cognitive functions. Among the latter, special importance is attached to the glutamatergic system.

It is known that glutamate receptors play an important role in the development of the central nervous system, modulating the processes of neuronal migration, ensuring their survival and the formation of neuronal networks. These receptors are divided into ionotropic, associated with ion channels, and metabolototropic, inducing changes in metabolic processes. A characteristic feature of ion -otropic NMDA-class receptors is the inherent function of regulating the conductivity of ion channels for CA2 +. Due to this, NMDA-receptors play an important role in regulating the duration of the exciting potential, thereby participating in the implementation of cognitive functions, mediating such processes in the brain as learning, coordination, and memory.

Treatment of vascular cognitive disorders

The spectrum of therapeutic effects aimed at the treatment and prevention of progressive disorders of cognitive functions is wide enough and includes the following types of therapy: antiaggregant, antihypertensive, and also aimed at stimulating the processes of neuroplasticity and correction of neuro-medical disorders. The latter areas include cholinergic therapy, the use of neurotrophic drugs, correction of glutamatergic neurotransmission disorders. One of the drugs that correct the state of the glutamatergic system is memantine hydrochloride.

Memantine hydrochloride is a potential-dependent, non-competitive M-methyl-B-aspartate (NMDA) receptor antagonist with an average affinity. It blocks calcium currents, enhances the utilization of glucose in the brain and the release of dopamine, has neuroprotective properties, increases the resistance of mitochondria to hypoxia, and slows down the processes of neurodegeneration. By blocking the activity of ion channels at low concentrations of glutamate and interacting with the receptor when it is in the "open" state, memantine hydrochloride does not disrupt the physiological activation of the NMDA receptor necessary for the effect of long-term potentiation and memory consolidation. The clinical efficacy of the drug was noted in many patients with varying degrees of cognitive impairment.

Thus, memantine hydrochloride, possessing neuroprotective properties, entered clinical practice as a drug capable of improving the condition of patients with cognitive impairment.

The aim of the study was to study the effectiveness of the memantine hydrochloride preparation in patients with cognitive impairment that developed after an acute cerebrovascular accident (2-3 months after the ONMC) and after an ischemic or hemorrhagic stroke (1-2 years after the ONMC).

The tolerability, effectiveness and safety of the course therapy of memantine hydrochloride ("Mema", Actavis) was studied according to the scheme: 5 mg only in the morning for 5 days, then 5 mg 2 times a day for 3 months in patients with ONMI and in patients who underwent ischemic or hemorrhagic stroke in an anamnesis with the presence of cognitive impairment.

The study included 60 people between the ages of 47 and 78 who had an acute cerebral event, in the background of which they had various cognitive disorders. Patients were divided into 2 groups: the main group (n = 30) received memantine hydrochloride according to the scheme against baseline therapy; Control group (n = 30) received basic therapy (metabolic, decongestant).

Neuropsychological testing was aimed at identifying such cognitive disorders as memory impairment, attention, concentration, mental performance, psychomotor functions. Objective assessment of cognitive impairment was performed using a set of neuropsychological tests. Mental state was determined by MMSE (mini-study of mental state), according to the test of 10 words, Isaac's test, 3A33O-ZCT test at the beginning of therapy, 1 month and 3 months later. Side effects of the drug were recorded during the entire period of observation of patients.

MRI of the brain was performed by patients in the hospital to confirm the presence of an ischemic or hemorrhagic stroke in the anamnesis.

In patients of both groups, vascular events developed against the background of AH, cardiac rhythm disturbances, diabetes mellitus, atherosclerosis. There were no statistically significant differences between the groups for these indicators.

In the main group of cognitive impairments, hemorrhagic stroke was observed in 4.5% of cases, ischemic stroke in 22.7% of cases, lacunar conditions in 18.2% of cases, with the consequences of hemorrhagic stroke in 9.1% of cases, the consequences of ischemic stroke - in 31.8% of cases, against a background of chronic cerebrovascular accident of the 2-3rd degree - in 13.6% of cases.

At admission, patients complained of weakness in the extremities with impaired motor functions in them, speech impairment (blur, blurred pronunciation of some sound combinations), dizziness, headache of various character and localization, aggravated by psychoemotional and physical stress, memory loss, attention disturbance, mood , impossibility to concentrate, quick fatigue, psychoemotional instability with a predominance of depressive background. Some patients noted a disturbance in the rhythm of sleep, which became superficial, with frequent awakenings.

Focal symptoms were represented by motor disorders: mono- and hemiparesis of varying severity, sensory disorders (hypoesthesia of pain sensitivity by mono- or hemitip), speech disorders (elements of motor aphasia, dysarthria), oculomotor disorders, decreased pharyngeal reflex; observed symptoms of cerebellar disorders (diffuse muscle hypotension, static-locomotor ataxia), oral automatism.

Evaluation of the dynamics of cognitive functions in patients with vascular events in the treatment with memantine hydrochloride was carried out with the help of MMSE. During the treatment, significant changes in the degree of cognitive impairment were noted.

Evaluation of the state of long-term memory, fatigue, attention activity was determined using a test of 10 words. A large number of "superfluous" words indicate disinhibition or disorders of consciousness. When examining adults for the third repetition, the subject with normal memory usually reproduces correctly to 9 or 10 words. The memory curve may indicate a loss of attention, a marked fatigue. Increased fatigue is recorded if the subject immediately reproduced 8-9 words, and then each time less and less. In addition, if the subject reproduces fewer and fewer words, this may indicate forgetfulness and absent-mindedness. In the main group of patients who received memantine hydrochloride before treatment, the results were significantly improved.

In the control group, the improvement was not so pronounced.

With the help of a set of Isaac's tests on speech activity, the ability to reproduce word lists for 4 semantic categories was evaluated, the maximum result was 40 points. In the patients of the main group there was a decrease in the level of speech activity before treatment, after 3 months it reached the norm. In all patients there was a repetition of the same words, the use of words from other semantic categories.

In the proof-of-effect test, Zazzo, the speed of the task before the start of treatment indicated a decrease in concentration and performance in general; it increased by the 3rd month of treatment.

The obtained results testify to the effectiveness of the use of memantine hydrochloride in the complex therapy of cognitive impairment in patients with acute cerebral vascular events (2-3 years after the ONMC), their consequences (1-2 years after the ONMC). The use of memantine hydrochloride is safe and is not accompanied by pronounced side effects. It affects the central mediator processes, contributes to the regress of existing cognitive impairment, reduces the accompanying emotional-affective and behavioral disorders and improves the quality of life of patients.

After the treatment, there were changes in the cognitive status of patients. The MMSE scores improved by an average of 4.5 points (up to 29.45 ± 0.19 points) in the main group and by 1.8 points (up to 27.44 ± 0.27 points) in the control group. No dynamics of symptoms of organic brain damage was observed. Some patients reported an increase in overall motor activity. In Isaac's test, repetitions of the same words stopped, the speed of the test was significantly increased in patients who received memantine hydrochloride. Also in the patients of this group, in the test of the proof sample of Zazzo, in all cases a significant increase in the rate of performance of the task and a reduction in errors were recorded, which indicates an increased concentration of attention and improved performance in general compared to the control group. The received results testify to high efficiency, good tolerability and rather long therapeutic effect of memantine hydrochloride.

Thus, the use of NMDA receptor antagonists is a valid and effective method for the complex treatment of cognitive impairment. Considering the complex nature of the action of memantine hydrochloride on cognitive functions, daily activity, emotional and somatic state, its administration to patients with cerebral vascular events can be recommended for widespread use.

Prof. VA Yavorskaya, OB Bondar, T. X. Mikhayelyan, Yu. V. Pershina, Cand. Honey. Of Sciences BE Bondar // International Medical Journal - №4 - 2012