All about Actovegin: what is it prescribed for and how to use it

Analogs and cheap substitutes

The only generic (non-patented analogue) of Actovegin is the drug Solcoseryl (the same active ingredient and indications for use and almost the same cost of 600-1700 rubles, depending on the form of the drug).

Actovegin is produced in Austria by a branch of the Swiss pharmaceutical company Nykomed, and Solcoseryl is produced in Germany. The drugs are made from the blood of Austrian and German calves, but in no Western European country is this medicine allowed not only for use, but also for sale.

It is also worth remembering that cattle are susceptible to so-called slow prion infections (including “mad cow disease,” to which humans are susceptible). The pathogen can enter the body through parenteral administration of the drug; it is stable to high temperatures and antiseptics. Prion infection proceeds slowly (the incubation period can reach 8 years), and the clinical manifestations are disguised as other diseases. A case of release of a batch of Actovegin from raw materials that did not undergo appropriate control was registered.

Conditional analogues of Actovegin on the Russian market:

• Cerebrolysin;
• Cortexin;
• Mildronate;
• Mexidol.

The incidence of chronic cerebrovascular accident is determined to be 70-100 cases per 1000 population [8], and impaired cognitive function is recognized as one of the most common manifestations of cerebrovascular disease. According to population studies, the initial manifestations of this disorder are detected in 24.4% of the urban population of elderly and senile age (60 years and older), and among elderly patients observed in a psychoneurological clinic - in 18.7% [1]. During a comprehensive examination of elderly patients at a territorial clinic, these disorders were found in 30.8% [6]. Mild cognitive impairment (MCI) as part of vascular psychoorganic syndrome in 24.5% of cases is the reason for contacting a gerontopsychiatrist at a general somatic clinic, and in another 36.2% of cases it is diagnosed as a comorbid disorder in patients of a gerontopsychiatric office [6 ].

MCI[] syndrome is characterized by a borderline disorder of memory and cognitive functions, the degree of manifestation of which does not allow a diagnosis of dementia of cerebrovascular or other origins, including Alzheimer's disease (AD) [2].

The prevalence of MCI syndrome in old age is extremely high. Among the Moscow population over 60 years of age, this figure is about 18% [4]. Similar figures (19%) are given by O. Lopez et al. [15]. As has been shown by domestic researchers [9], 40% of people with an established diagnosis of MCI are diagnosed with AD or dementia of another origin within 4 years.

In recent years, evidence has been obtained of the heterogeneity of the MCI syndrome, and therefore various clinical variants of the syndrome have been identified (amnestic, non-amnestic and variant with multiple cognitive impairment), which have a different prognosis in terms of the likelihood of transition to different nosological types of dementia (AD, vascular or frontal dementia). temporal dementia, dementia with Lewy bodies, etc.).

A high risk of worsening cerebral vascular disease, including an increased risk of cerebrovascular accidents, as well as the risk of developing dementia even without stroke, is most often associated with MCI syndrome with multiple cognitive impairment [5, 15].

In this regard, the tasks of treating MCI of vascular origin in elderly and senile patients have become the most pressing in geriatric practice and constitute the daily content of the activities of both neurologists and psychiatrists, as well as general practitioners [12, 14]. Treatment of the initial manifestations of cognitive decline is one of the most important tasks of complex therapy, including the prevention of dementia in the elderly.

Current treatments for initial cognitive decline of vascular origin include improving blood rheology, improving the delivery and use of oxygen and glucose in cerebral structures; reduction of neurotransmitter deficiency.

Actovegin, used for the treatment and prevention of hypoxic and ischemic disorders of organs and tissues, belongs to the group of drugs without direct vasodilating effects. The drug acts as a neurometabolic stimulant, increasing the energy supply of nerve cells by increasing the consumption and utilization of oxygen and glucose, which leads to improved brain function.

Actovegin is a highly purified hemodialysate obtained by ultrafiltration from the blood of young bulls under the age of 6 months. The drug contains exclusively physiological components with high biological activity - organic low-molecular compounds: amino acids, oligopeptides, nucleosides; intermediate products of carbohydrate and fat metabolism: oligosaccharides and glycolipids. The molecular weights of the organic compounds that make up Actovegin do not exceed 5000 daltons. The technology for obtaining hemodialysate excludes the presence of protein and other components with antigenic and pyrogenic properties. Experimental and clinical studies have proven that Actovegin does not contain additional impurities of blood components.

The therapeutic effectiveness of Actovegin is due to a wide range of substances included in its composition: amino acids, oligopeptides (insulin-like action), nucleosides, electrolytes (potassium, sodium, phosphorus, magnesium, calcium, copper) and microelements, as well as intermediate metabolic products (oligosaccharides, glycolipids).

Numerous studies have shown that Actovegin, by improving the absorption of oxygen and glucose by nerve cells, has an activating effect on metabolic processes in the brain. When glucose consumption increases, oxygen consumption increases accordingly. These processes lead to the acceleration of ATP synthesis in the brain, stimulation of cellular metabolism, and improvement of blood supply to ischemic brain tissue, which provides a clear therapeutic effect for cerebrovascular accidents.

The supply of large amounts of oxygen causes activation of aerobic oxidation, which in turn increases the energy potential of the cell. Actovegin improves energy exchange in the vascular endothelium, which leads to the release of endogenous substances with vasodilating properties - prostacyclin and nitric oxide - and improved perfusion of all tissues and a decrease in peripheral resistance. In conditions of tissue hypoxia caused by impaired microcirculation, Actovegin promotes the restoration of the capillary network due to newly formed vessels. By improving oxygen delivery and reducing the severity of ischemic tissue damage, Actovegin promotes the protein-synthesizing function of cells.

The effect of Actovegin is most pronounced under conditions of intracellular oxygen deficiency, in particular due to hypoxia or hypoperfusion, and the antihypoxic effect of Actovegin extends not only to neuronal, but also to glial structures. The effect of Actovegin begins to manifest itself no later than 30 minutes (10-30 minutes) after parenteral administration and reaches a maximum after an average of 3 hours (2-6 hours).

Due to the fact that Actovegin improves microcirculation and has an activating effect on metabolic processes in the brain, it seems reasonable to study its effectiveness in elderly patients with cognitive impairment of vascular origin. Although Actovegin has been known for about 40 years as a classic neurometabolic drug, its attitude towards nootropic properties has fluctuated from doubts to evidence-based statements. A number of controlled studies [6, 7, 9, 12, 15, 17, 19] have shown the effectiveness of Actovegin in cognitive disorders of varying severity, including dementia of vascular and Alzheimer's origin [7, 9, 12]. Most studies show the benefits of parenteral administration of Actovegin by intravenous infusion of 250 ml (2000 mg) in a course of at least 10 infusions; however, a faster onset of effects on cognitive impairment is indicated. Reduction or leveling of memory and attention disorders, an increase in the pace of mental processes are recorded in more than half of the patients. There are no data on the results of another method of parenteral administration of Actovegin - intramuscular, which is much more convenient for widespread use in outpatient practice.

The purpose of this work is to study the effectiveness and safety of intramuscular use of Actovegin in elderly patients with mild cognitive decline syndrome of cerebrovascular origin.

Material and methods

The study was conducted as an open, uncontrolled study in a group of patients with MCI syndrome of vascular origin, under the supervision of employees of the Department of Alzheimer's Disease and Associated Disorders of the Department of Geriatric Psychiatry of the Scientific Center for Mental Health of the Russian Academy of Medical Sciences.

Inclusion criteria

patients in the study: women (postmenopausal) and men aged 50 to 85 years;
MMSE score ≥26 points; compliance with the operational criteria for the diagnosis of mild cognitive decline syndrome (MCI) (patient complaints of memory loss, confirmed by an informant - usually a family member, and objectively detected signs of mild cognitive dysfunction; score 0.5 on the CDR scale; no basis for a diagnosis of dementia; preservation of daily activities , although slight deterioration in complex and instrumental types of daily and/or professional activities is possible); Hacinski scale score >4 points; obtaining written informed consent from the patient. Exclusion criteria
: diagnosis of dementia according to DSM-IV, ICD-10 criteria; other organic diseases of the nervous system, congenital and/or acquired metabolic encephalopathies, toxic and drug encephalopathies, Parkinson's disease, stroke, epilepsy, infectious diseases, demyelinating and hereditary degenerative diseases of the central nervous system); neoplastic and/or traumatic brain injury; systemic diseases; severe organ pathology: malignant extracerebral, HIV infection, diabetes mellitus in the stage of decompensation or other endocrine diseases; alcoholism and/or drug dependence; drug or other intoxication; depression with a score >18 on the Hamilton Depression Scale; systolic pressure level >180 mm Hg, diastolic >95 mm Hg; deficiency of folic acid and/or vitamin B12; hypothyroidism; treatment with procognitive agents for 4 weeks before or during the study.

At the end of the run-in period, which lasted up to 7 days, patients were prescribed Actovegin at a dose of 200 mg (5 ml) intramuscularly, and treatment continued for 28 days.

Concomitant therapy was allowed to use short-acting benzodiazepine drugs and drugs aimed at treating somatic pathology if therapy with them began 1 month before the present study and continued throughout the study in stable doses.

The assessment of the patients' condition during treatment using scales was carried out on fixed days: day 0 (before the start of therapy), day 14 of the study, day 28 of the study (end of the treatment course), day 56 (follow-up period).

Before and during the study, the following methods of examining patients were used: objective clinical examination, ECG, laboratory blood and urine tests.

In accordance with the recommendations of S. Kanowski [14], the effectiveness of a nootropic drug should be assessed in three areas: psychopathologically (assessment of clinical symptoms); psychometrically (testing); by behavior (self-esteem and assessment by others, taking into account age characteristics).

The following scales and tests were used to assess the state of cognitive functions and daily activity of patients: CGI (Clinical Global Impression Scale), MMSE, Speech Performance Test, Frontal Dysfunction Scale, Clock Drawing Test, Boston Naming Test, Mattis Dementia Scale, 10 Word Memory Test , Hamilton Depression Scale. The safety of the drug was assessed using an adverse event rating scale.

The study included 30 patients, 7 men and 23 women aged from 53 to 84 years (average 71.2±8 years), who were undergoing inpatient or outpatient treatment.

The age of the patients at the onset of the disease ranged from 52 to 81 years (average 67.8±7.9 years). The duration of the disease in all cases (with the exception of one) coincided with the duration of the psychopathological state that was the indication for the prescription of Actovegin, and ranged from 1 year to 7 years (on average 3.3 years).

All patients with sufficiently long duration of disorders that met the criteria for MCI syndrome had no signs of obvious progression of cognitive impairment. In all cases, the score on the General Deterioration Scale - GDS (Global Deterioration Scale) corresponded to point 3, which reflects the most initial manifestations of the disease [18]. The assessment of cognitive status according to the Clinical Dementia Rating - CDR (Clinical Dementia Rating) in all cases did not exceed 0.5 points, which excluded or made the diagnosis of dementia doubtful due to the mild degree of the disorder. According to the Clinical Global Impression - Severity (CGI-S) scale, the severity of the patients’ condition was classified as “borderline disorder” in 10 patients, and in the remaining 20 observations - as “mild illness”.

In 3 cases, mild cognitive impairment was combined with comorbid depression of mild severity (14-16 points on the Hamilton Depression Scale - HAM-D). Another 12 patients had individual depressive symptoms (5-13 points on HAM-D) , the totality of which did not meet the criteria for depressive syndrome, and their manifestations coincided with somatic complaints or overlapped with asthenic symptoms.The average group total score before the start of treatment with Actovegin according to HAM-D was 9.1.

The psychopathological history, along with mild cognitive decline and pseudoneurasthenic disorders, in 5 patients revealed time-bound episodes of psychopathological disorders that occurred 2-3 years before inclusion in the present study. One patient had experienced delirium in the past, another developed depression after an acute cerebrovascular accident (ACVA), and another 3 patients had previously reported psychogenic depressive reactions.

Determination of the neurological history revealed that 9 patients had previously suffered strokes - in 5 cases in the form of transient ischemic attacks (TIA), the remaining 4 patients suffered ischemic strokes (in one of these cases - again). The Hacinski scale score at the beginning of the study ranged from 4 to 10 points (average 6 points). The neurological diagnosis of all patients included in the study was formulated as stage 1-2 dyscirculatory encephalopathy [10].

The condition of the patients before starting treatment with Actovegin was characterized by a complex of symptoms of varying nature and varying degrees of severity. Common to all was a combination of signs of mild cognitive decline and asthenic (pseudoneurasthenic) disorders expressed to varying degrees and extent.

The reason for seeking medical help was primarily complaints of forgetfulness and various manifestations of asthenia. Manifestations of forgetfulness were described by patients as difficulties in memorizing or recalling, loss of natural ease in choosing words, “as if something had stopped.” Patients complained of absent-mindedness, slowed intelligence, admitted that it was “not easy for them to collect their thoughts” and remember recent intentions, especially when attention was distracted, but, as the patients noted, they could subsequently spontaneously remember what was necessary. Most patients, with rare exceptions, complained of frequent or constant headaches, sometimes only in one half of the head, but more often without clear localization, or heaviness in the head, described painful sensations in the head in the form of “tightening with a hoop” or “pressure on the eyes, on your ears." In addition, many patients complained of constant “ringing” in the ears, noise, and “hum” in the head.

The next most common complaints were unsteady balance, unsteadiness when walking, or a feeling that “the ground is falling away from under your feet.” In addition, patients noted the rapid onset of fatigue after light exertion, even after eating, making the bed, fatigue and decreased performance, weakness with a desire to lie down. The deterioration of general well-being was accompanied by sleep disturbances, difficulty falling asleep, a decrease in the depth and duration of sleep, abundant vivid dreams of sometimes frightening content or tiresomely changing meaningless content, in some observations with hypnagogic visual illusions of perception. Morning awakening was characterized by difficulties in the transition from sleep to wakefulness, and a lack of feeling of rest after sleep. Some patients complained of daytime sleepiness and drowsiness that interfered with their usual activities.

Patients noticed the appearance of tearful touchiness or heightened sensitivity to ordinary impressions from what they saw or heard. Mood instability was characterized by the ease of reactions of irritation and impatience; patients often noticed an increase in these manifestations after a restless night with frequent awakenings. A tendency toward a pessimistic assessment of everyday phenomena and life events could be combined with an influx of unaccountable anxiety and worry. The content of anxious fears often determined the appearance of forgetfulness and concentration on the disease as a whole or individual disorders.

In the mental state, manifestations of bradyphrenia were revealed with a slow pace of thinking and speech, difficulties concentrating attention, its instability and exhaustion, which was clearly revealed during testing and was manifested by difficulties in maintaining an activity program, distractibility, forgetting a task, and a slow pace of completion. At the same time, the patients willingly underwent the testing procedure, and when they noticed their mistakes or when shortcomings were pointed out, they lamented or sadly ironized about the weakening of memory or intelligence. Initial manifestations of difficulties in naming the proposed objects or images were compensated for by replacing or describing their purpose, while a minimal sound prompt quickly led to the desired result. Hesitations and pauses when choosing words, slowness of speech were combined with thoroughness and excessive detail, getting bogged down in details or with repeated repetition of what has already been said. Emotional lability was manifested by episodes of tearful weakness against the background of a predominantly complacent background of mood or the emergence of anxiety against the background of low mood.

Basic clinical and demographic data regarding the examined patients are presented in Table. 1

.

Magnetic resonance imaging (MRI) of the brain in the vast majority of patients revealed: expansion of the subarachnoid spaces - in 25 (83.3%) patients out of 30 and enlargement of the cerebral ventricles - in 26 (86.7%) patients. In 18 (60%) patients, post-ischemic foci of small volume located periventricularly were found: single up to 1.5 cm in diameter in 7 (23.3%) patients or multiple small ones in 11 (36.7%) patients. Leukoaraiosis was noted in 19 (63.3%) cases. In general, according to MRI data, signs of dyscirculatory encephalopathy were confirmed in almost all patients.

In the patients included in the study, the polymorphism of the apolipoprotein (ApoE) genotype was determined using a blood test. In two thirds of the observations, patients had the ApoE4(-) genotype with the following distribution of &egr;2 and &egr;3 alleles: 3.3, 3.2, 2.3 (51.9, 3.7 and 11.1%, respectively). 7 patients (25.9%) had the ApoE4(+) genotype, including 3.4, 4.4 and 2.4 (25.9, 3.7 and 3.7%, respectively). Various types of somatic pathology were identified in the patients included in the study (Table 2)

.
80% of patients suffered from arterial hypertension. More than half of the patients were diagnosed with coronary heart disease; in one third of these cases, disturbances in cardiac conduction and rhythm were noted.

results

Clinical positive dynamics in the process of treatment with Actovegin was expressed in a decrease in complaints, patients about “gained strength.” The feeling of dizziness, according to them, occurred noticeably less frequently, the unsteadiness of gait and instability of balance disappeared. In a number of cases, a decrease in the painful sensation of noise in the head or ears was also noted. Patients also noted improved night sleep, decreased fatigue, and increased activity and performance. The improvement in mood was accompanied by a decrease in the level of anxiety and de-actualization of overvalued fears (according to the patients, “it was as if they were wearing a filter”). While forgetfulness remained, patients showed a lesser tendency to fixate on these manifestations.

It was noteworthy that already from the 2nd week of treatment in patients whose condition before the start of therapy showed signs of subdepression or individual depressive symptoms, the general background of mood improved, and this positive dynamics persisted until the end of the course administration of Actovegin and even a month after its ending.

Along with a decrease in complaints, a reduction in asthenic disorders, restoration or increase in emotional stability, disturbances in cognitive functioning experienced significant positive dynamics. First of all, this relates to improving concentration and reducing inhibition. The acceleration of the pace of mental activity was manifested in faster answers to questions and an improvement in the pace of activity when completing test tasks. In some cases, there was a clear decrease in the torpidity of thinking and the manifestations of bradyphrenia in general. Activity and initiative in conversation and communication increased, and daily activities were restored to the required extent. The manifestations of speech difficulties decreased, hesitations and pauses disappeared in spontaneous speech, and patients coped with naming faster and better. Dysmnestic disorders noticeably decreased in their severity, which was reflected in an increase in the volume of memorization or in a greater ease of reproducing consolidated information. It is important to note that this effect turned out to be quite stable and persisted a month after completion of Actovegin administration, when patients did not receive any other treatment other than maintenance therapy for somatic diseases.

Changes in the condition of patients during therapy and during the follow-up period are shown in the figure.

.
Figure 1. Effectiveness of Actovegin therapy according to the CGI scale. 1 - minimal deterioration, 2 - no improvement, 3 - minimal improvement, 4 - moderate improvement, 5 - marked improvement. An improvement in the general clinical condition in the studied group of patients by the 14th day of therapy was noted in 96.7% of cases, including minimal improvement in 73.4% of patients and moderate improvement in 23.3% (see figure)
. In 1 patient, by the 14th day of treatment, the condition slightly worsened. By the time the course of therapy was completed (28 days), the overall frequency of improvement of varying degrees of severity remained the same (96.7%), however, moderate improvement was found in 66.7% of patients, pronounced improvement was achieved in 13.3% of patients, and only in 16.7% of patients showed minimal improvement. In 1 patient the condition did not change. 28 days after the end of the course of treatment, i.e. on day 56, the rate of improvement of varying severity was 100%. Moderate improvement was observed in 76.7% of patients, pronounced improvement was found in 13.3% of cases, minimal improvement in 10% of cases.

There was a statistically significant improvement on the MMSE scale ( p

<0.01) cognitive functions at each stage of the course of therapy: before treatment - 26.8±1.3 points, after 14 days - 28.0±1.3 points, after 28 days - 28.5±1.0 points and on the 56th day - 28.6±1.2 points.
Compared with the period before treatment, all indicators reached a degree of statistical significance ( p
<0.01). Moreover, by the 56th day of the study (28 days after completion of the course of treatment), the total score on the scale turned out to be even higher than the score at the end of the course of therapy.

There was a statistically significant increase in the number of words named within 1 minute (starting with the letter “k”): on the 14th day - 14.2±3.9; on the 28th day - 14.7±3.9 and on the 56th day - 15.5±2.5 compared to the period before treatment - 11.3±3.9 ( p

<0,01).

There was a significant improvement on the frontal dysfunction scale ( p

<0.01) was noted in the “Conceptualization” and “Sound Associations” tests - by the 14th and 28th days of the treatment course, as well as by the 56th day of the study, i.e.
28 days after the end of Actovegin administration (Table 3)
.
Scores on the tests “Simple choice reaction” and “Complicated choice reaction” reached a statistically significant value by the time the treatment course was completed ( p
<0.01). There was no improvement in the total score on the Dynamic Praxis test.

The clock drawing test score improved statistically significantly ( p

<0.01) at each stage of the course of therapy and after completion of treatment: before treatment - 8.3±1.8; 14th day - 9.1±1.6; 28th day - 9.3±1.5; 56th - 9.6±1.1.

According to the Boston Naming Test, the total group number of independent correct answers statistically significantly improved ( p

<0.01) at each stage of the course of therapy and after completion of treatment: before treatment - 42.7±6.8; on the 14th day - 46.2±5.6; on the 28th day - 49.1±5.1; on the 56th day - 49.5±5.4.

According to the Mattis Dementia Scale in the “Similarities” and “Memory” tests, there was a statistically significant improvement ( p

<0.01) was noted on the 14th and 28th days of treatment, as well as after 4 weeks of follow-up
(Table 4)
.
There was no improvement in total scores on the “Reciprocal Coordination” and “Graphomotor Test” tests.
According to the 10-word memorization test, there was a statistically significant improvement in total scores during 1, 2, and 3 attempts to memorize words ( p

<0.01) was noted on the 14th and 28th days of the course of treatment, as well as on the 28th day of follow-up
(Table 5)
.
A statistically significant improvement in the total assessment of delayed word recall was achieved by the 28th day of therapy.
The statistically significant level of its improvement remained after 4 weeks of follow-up observation, although the degree of improvement in the total assessment decreased somewhat. According to the HAM-D scale, a statistically significant improvement in the total group score is M±SD ( p

<0.01) was noted by the 14th day - 5.8±3.2 points and the 28th day - 3.9±3.1 points of the course of treatment, as well as by the 28th day of follow-up - 3.9 ±3.7 points compared to the period before treatment - 8.8±4.5.

There were no adverse events during treatment with Actovegin during the study.

Discussion

The incidence of mild cognitive impairment, not reaching the level of dementia, is extremely high among elderly patients in general somatic institutions. However, there is a certain paradox in the clinical thinking of internists, when a diagnosis of cerebrovascular disease is easily made, often only on the basis of so-called “vascular” complaints and nonspecific neurological symptoms, while complaints of elderly patients about forgetfulness or statements of dysmnestic disorders are regarded as age-related characteristics of cognitive status. Accordingly, medical prescriptions are limited to the prescription of antihypertensive therapy, less often in combination with antiplatelet agents and vasodilators, and the correction of cognitive impairment is considered an optional measure, sometimes left to the discretion of patients.

Assessing the condition of patients urgently requires the study of cognitive functions, especially since complaints of elderly people about weakened memory, impaired ability to concentrate, decreased productivity, and fatigue are often the leading ones when visiting a doctor and determine the search for help.

In the genesis of cognitive impairment, a predominant role is given to ischemic brain lesions, both focal and diffuse, with special importance attached to subcortical lesions. One of the main pathogenetic factors is arterial hypertension (AH) and vascular lipohyalinosis. In these conditions, when there is a decrease in blood pressure or circadian blood pressure fluctuations, heart failure, or inadequate antihypertensive therapy, hypoperfusion occurs in the areas of the terminal circulation (deep structures). A marker of the presence of chronic ischemia is leukoaraiosis as a neuroimaging sign of demyelination, gliosis, and expansion of perivascular spaces.

The leading role in the pathogenesis of cognitive disorders of vascular origin is played by damage to the deep parts of the white matter and basal ganglia, which leads to disruption of connections between the frontal lobes and subcortical structures (disconnection phenomenon).

The results of an open, uncontrolled study of the effectiveness of a course of treatment with Actovegin with daily intramuscular administration of the drug at a dose of 200 mg demonstrated a significant improvement in the condition of the vast majority of patients with MCI syndrome of vascular origin. There was a significant improvement in group average indicators in almost all tests used to assess cognitive dysfunction. It should be noted that the drug in the studied dosage form has an undoubted effect on improving concentration, accelerating the pace of mental activity and memory processes.

The data obtained correspond to the indications given in the literature on the improvement of cognitive functions in cerebrovascular insufficiency under the influence of treatment with Actovegin [6, 7, 10, 17]. Although it is not possible to reasonably judge the antidepressant properties of the drug, one cannot ignore the fact that during treatment with Actovegin there was a decrease in the severity or disappearance of depressive symptoms, especially since none of the patients received antidepressant therapy during the period of treatment with Actovegin. A decrease in the severity of affective disorders as a result of treatment with Actovegin was previously noted in a study by Kuntz (2004), where depressive disorders were detected in 53.3% of patients with MCI.

Of particular interest is the fact that the positive therapeutic effect continued to increase after the end of the Actovegin therapy course, which indicates not only the persistence of the improvement, but also its possible impact on the mobilization of compensatory mechanisms.

[]MCI syndrome in a number of works by domestic neurologists [3] is called moderate cognitive disorder (MCI).

conclusions

At the moment, Actovegin has not undergone a single study according to the GHP rules (the international code of quality medical practice that guides scientists in conducting clinical trials). But at the same time, the company producing the drug does not set such a goal, since a strong evidence base is not required for the fish to enter the main market (CIS countries).

According to studies of medical records of patients with hypertension who were hospitalized, it was revealed that the percentage of money spent on treatment with Actovegin averaged 17% of the total amount. This is irrational spending on a drug without an evidence base for hypertension and concomitant conditions, and its inclusion in the prescription lists is impractical.

Actovegin

Actovegin belongs to the group of antihypoxants, i.e. drugs that help body cells store oxygen and reduce the need for it. The pharmaceutical raw material for the production of Actovegin is calf blood serum extract. By activating the cellular metabolism of oxygen and glucose and optimizing their consumption, the drug significantly increases the energy capabilities of cells and their resistance to oxygen starvation. When using Actovegin, the synthesis of ATP, the main energy “fuel” of the body, increases 18 times. Thus, all energy-consuming processes in cells are intensified (regeneration). At the same time, Actovegin increases the body's concentration of amino acids aspartate, glutamate, and gamma-aminobutyric acid, which promotes, for example, the rapid healing of wounds and other skin damage.

The method of using Actovegin is determined by its release form. Tablets are taken three times a day before meals along with a small amount of water, 1-2 pieces. Duration of treatment is 1-1.5 months. Actovegin solution is injected into a vein, muscle or artery. The initial dose is 10-20 ml per day, then the dose is reduced to 5-10 ml. The duration of treatment depends on the specific disease, for example, for disorders of cerebral circulation and metabolism it is at least a month, for ischemic stroke - 3 weeks, for poorly healing ulcers and burns, they focus mainly on the speed of the healing process.

As for the external forms of release of Actovegin - cream, gel and ointment - in this case the drug is used externally: applied twice a day (this is the established minimum, more often is possible) for at least 12 days. For ulcers, wounds and inflammatory skin diseases, treatment begins with 20% gel and 5% cream, then moves on to 5% ointment (the so-called three-step treatment). In order to prevent bedsores, external forms of Actovegin are rubbed into the skin in the most disadvantaged places in this regard.

When using Actovegin in the form of an injection solution, you should be aware of a number of important circumstances. Thus, when using the drug intramuscularly, it is allowed to administer no more than 5 ml of solution. To prevent allergies, it is recommended to do a test injection (2 ml of solution intramuscularly). No preservatives are used in the production of injectable Actovegin, so injections must be carried out in strict compliance with all aseptic conditions. And most importantly: the opened drug is not stored, and if not all of the solution was used from the open ampoule, then the remaining drug must be disposed of.

Indications

Actovegin ointment, the price of which is affordable, is prescribed in the presence of damage to the skin in order to speed up healing. The product is indicated for the treatment of any wounds. These can be cuts, scratches, etc. It is used to treat inflammatory processes, radiation injuries on the skin and mucous membranes

Indications for use of the product are:

• Trophic ulcers that occur with varicose veins or diabetic angipatia.
• Bedsores caused by prolonged immobility of seriously ill patients.
• Burns that can occur as a result of thermal or chemical exposure, or during prolonged exposure to the sun.

Peculiarities

1. Actovegin ointment belongs to a group of drugs that accelerate tissue regeneration processes. It is a white substance with a uniform consistency. The product is supplied in aluminum tubes of various sizes.
2. The active component in Actovegin ointment is a deproteinized hemoderivative. This is a natural component that is obtained from the blood of calves during dialysis and ultrafiltration. The natural substance contains more than two hundred biologically active substances. In this regard, it is impossible to accurately describe the mechanism of action of the drug. The main substances in the composition of the hemoderivat:

• Amino acids important for the body.
• Compounds of peptides and carbohydrates.
• Nucleotides.
• Cholesterol.

1. All of these components are natural to the human body, so the drug is well tolerated.
2. Actovegin ointment has a pronounced antihypoxic effect. That is, when using the ointment, it is possible to compensate for the lack of oxygen in tissue cells, and, therefore, accelerate the regeneration processes. In addition, the use of the product increases the concentration of amino acids, improves blood circulation and normalizes metabolism at the cellular level.

When to use them

Most often, nootropics appear in the prescriptions of neurologists. They are prescribed for everything - from neurosis and OCD, from VSD, which does not exist, and dementia. In hospitals, nootropic drugs are administered intravenously to speed up tissue recovery after a stroke or transient ischemic attack - as prescribed by clinical recommendations. But they do not recommend using some nootropics during the acute period of ischemic stroke due to possible neuronal depletion and steal syndrome. Therefore, focusing only on them is not enough.

“First, the doctor makes a generally accepted diagnosis,” says GMS Clinic neurologist Sergei Makarov. — If we are talking about vascular cognitive impairment, then first of all the risk factors are corrected: diabetes mellitus, atherosclerosis and arterial hypertension. Not all diseases require medication."

But many neurologists and psychiatrists, who are not interested in new research, prescribe nootropics to people with impaired memory, attention and learning ability, focusing only on clinical recommendations. For example, Cerebrolysin is recommended for the prevention of dementia at the initial signs of Alzheimer's disease. Also, many doctors believe that nootropics will help you stay sane and memory longer in case of chronic vascular disorders of the brain.

“When a child has a disorder of psychoneurological development, the doctor is tempted to give something to “improve brain function,” says Varvara Khaletskaya, MD, neurologist at the Fantasy children’s clinic. “After all, sometimes there is no effective method leading to a complete recovery. Therefore, the doctor and the parent are trying to invest bit by bit: pedagogical correction, physiotherapy and medications.

It’s another matter when there is an effective treatment protocol, but the doctor continues to treat in his own way. It turns out ugly: instead of pedagogical correction, a child with psycho-speech disorders is given nootropic drugs, and they are advised to “wait” with classes. Or in the case of sensorineural hearing impairment, for which hearing aids are possible, they are referred to a neurologist to “feed” the auditory nerve. In this case, time is simply wasted. Before prescribing a treatment with insufficient evidence base, the doctor should make sure that there is a more effective solution.”

New aspects of the use of Actovegin: from mechanisms of action to clinical effects

The results of studies evaluating the effect of the drug Actovegin on the functional activity of the microvascular endothelium, in particular the functional state of the microvascular smooth muscle apparatus, are presented. Due to its endothelial protective properties, Actovegin can be used to correct endothelial dysfunction in neurological, therapeutic, endocrinological and surgical patients.

Currently, the universality of the mechanisms of cell damage under various types of pathological influences has been proven. The final link in inflammation, ischemia, and stress is a violation of redox reactions, metabolism and energy supply to cells [1]. Today, neuroprotection, neuroplasticity and neurogenesis are considered fundamental neurobiological processes that participate in the implementation of endogenous protective activity, resist pathophysiological damaging mechanisms and stimulate endogenous recovery [2].

The classical concept of neuroprotection involves suppression of individual pathophysiological mechanisms of damage when using an appropriate drug [3]. Impaired transport and utilization of glucose is one of the leading pathogenetic mechanisms of cell apoptosis. The action of various drugs is aimed at enhancing the delivery of glucose into cells, inhibiting the oxidation of long-chain fatty acids in mitochondria and indirectly enhancing the oxidation of glucose. This leads to an increase in the synthesis of adenosine triphosphate and the neutralization of oxygen radicals, the production of which increases under ischemic conditions [4].

Today, one of the best approaches to neuroprotection is the use of pleiotropic drugs. Pleiotropic action involves a simultaneous modulating effect on various damaging pathological mechanisms (hypoxia, oxidative stress, excitotoxicity, inflammation, apoptosis and many others) [3]. The drug of biological origin Actovegin has these properties.

Actovegin is a highly purified, protein-free derivative of calf blood, obtained by ultrafiltration and consisting of more than 200 biological substances. The molecular weight of the organic compounds that make up the drug does not exceed 5000 daltons [5]. The main components of Actovegin are amino acids, biogenic amines and polyamines, sphingolipids, hexoses, eicosanoids, succinate, choline, vitamins, adenosine monophosphate, inositol phosphooligosaccharides, as well as macroelements (magnesium, sodium, calcium, phosphorus) and neuroactive microelements (silicon, copper). The macro- and microelements that make up Actovegin are part of neuropeptides, enzymes and amino acids, and therefore are recognized and absorbed by neurons much better than macro- and microelements that enter the body in the form of salts.

The metabolic effect of Acto-vegin consists primarily of enhancing the utilization of oxygen and the transfer of glucose into cell mitochondria. Various experimental models have shown that Actovegin, by influencing oxidative phosphorylation in mitochondria, increases oxygen production by cells by almost 40% [6, 7]. In addition, Actovegin is able to enhance the transport of glucose into the cell. It was found that the active fraction of the drug, including inositol phosphooligosaccharides, activates the transport of glucose into the cell through the activation of transport proteins (GLUT1, GLUT4), without involving insulin receptors. This is of great clinical importance, for example, in type 2 diabetes mellitus against the background of insulin resistance [8].

Actovegin has a neuroprotective effect and, in particular, has a pronounced antioxidant effect. According to in vitro data, Actovegin improves metabolism in cells, increases the number of neuronal synapses, reduces the level of markers of apoptosis induction (caspase 3) and the formation of reactive oxygen species in cells. These effects are dose-dependent [9, 10]. Similar results were obtained in recent experimental work.

MM. Yurinskaya et al. (2014) found that the use of Actovegin leads to a decrease in apoptosis of human neuroblastoma cells induced by hydrogen peroxide and suppression of intracellular signaling pathways involved in the mechanism of cell death [11].

L.G. Khaspekov et al. (2014) [12], studying the protective effect of Actovegin in a model of glutamate toxicity, found that the drug at a dose of 1 mg/ml has a neuroprotective effect, expressed in a decrease in cell death and most likely associated with the action of glutamate in rat cerebellar neurons.

Actovegin also demonstrated a neuroprotective effect in severe neuropathy in a model of streptozotocin-induced diabetes in rats. According to A. Dieckmann et al. (2011), Actovegin significantly improved conductivity in sensory nerve fibers and reduced the activity of poly-ADP-ribose polymerase, a nuclear enzyme whose excessive activation can trigger cell death processes in conditions such as cerebrovascular diseases and diabetic polyneuropathy [13].

In a study by S. Mielin et al. (2014) on a model of total cerebral ischemia in rats with occlusion of four main arteries of the brain, Actovegin contributed to better survival of neurons in the CA1 zone of the hippocampus compared to placebo [14]. This observation was accompanied by a large number of surviving individuals in the Actovegin group and significantly better results in the Morris water maze test.

In addition to Actovegin’s ability to improve cellular metabolism and have a neuroprotective effect, a number of studies have noted the drug’s effect on the microvascular endothelium.

In a pilot study by A.A. Fedorovich on 28 healthy volunteers, it was revealed that Actovegin has a direct endothelial protective effect at the level of the microvascular bed [15]. The obtained results were subsequently confirmed in a population of patients with obliterating diseases of the arteries of the lower extremities, as well as with arterial hypertension.

According to the results of another study, intravenous infusions of Actovegin improved microcirculation parameters due to the endothelial protective effect and had a positive effect on the course of the disease. Patients receiving the drug were able to walk longer distances without pain [16].

The effectiveness of the drug was assessed in patients with arterial hypertension and moderate vascular cognitive impairment. Despite adequate lipid-lowering and antihypertensive therapy with the achievement of target blood pressure levels, cognitive disorders persisted in the comparison group (decrease in voluntary attention indicators), while in the Actovegin group it was possible to level out the cognitive deficit. In addition, during Actovegin therapy, a significant increase in the number of functioning capillaries at rest was noted, that is, a decrease in the elements of functional rarefaction of the microvasculature observed in patients with arterial hypertension [17].

V.V. Zakharov and V.B. Sosnin assessed the therapeutic effect of Actovegin on cognitive functions in patients with type 2 diabetes mellitus [18]. The patients were divided into two subgroups: the first - with the presence of concomitant arterial hypertension, signs of coronary heart disease and hemodynamically significant stenosis of the carotid arteries, the second - with the absence of the above pathology. After a three-month course of therapy, the greatest dynamics in indicators of concentration, short-term memory, visual-motor coordination and regulation of mental activity were observed in the group of patients in whom diabetes was combined with other clinically significant cardiovascular risk factors. Cognitive impairment in this category of patients, along with other factors, is based on tissue hypoxia caused by micro- and macrovascular damage. It is likely that Actovegin may have an additional positive effect in vascular cognitive disorders associated with damage to small vessels by improving microcirculatory parameters.

Thus, based on a number of experimental and clinical data, we can conclude that Actovegin, having many positive effects (antihypoxic, metabolic, neuroprotective and endothelial protective), is one of the promising drugs for the correction of hypoxic-ischemic damage, endothelial dysfunction, and microcirculatory disorders. Actovegin can be recommended as the drug of first choice for neurological and therapeutic patients: with acute or chronic cerebral ischemia and concomitant cardiovascular diseases, diabetes mellitus complicated by diabetic polyneuropathy, moderate and severe cognitive impairment in persons who have suffered a stroke. Therapeutic regimens used for the use of Actovegin in chronic ischemic conditions: 10–20 ml (400–800 mg) per 200 ml of saline intravenously in a course of seven to ten days, then one or two tablets (200–400 mg) three times a day within one to two months. In the presence of mnestic-intellectual disorders in elderly people - up to 12 weeks, two to three tablets three times a day. Repeat courses after six to eight months.

Actovegin solution for injection 40 mg/1 ml in 2 ml ampoules No. 5x5

Name

Actovegin solution.

Release forms

Injection.

FTG

Tissue regeneration stimulator.

Compound

1 ampoule (2 ml) contains Actovegin concentrate as an active substance (in terms of dry deproteinized calf blood derivative) - 80 mg, containing sodium chloride - 53.6 mg; excipient: water for injection – up to 2 ml. 1 ampoule (5 ml) contains Actovegin concentrate as an active substance (in terms of dry deproteinized calf blood derivative) - 200 mg, containing sodium chloride - 134.0 mg; excipient: water for injection – up to 5 ml. 1 ampoule (10 ml) contains actovegin concentrate as an active substance (in terms of dry deproteinized calf blood derivative) - 400 mg, containing sodium chloride - 268.0 mg; excipient: water for injection – up to 10 ml.

Description

A clear, yellowish solution, practically free of particles.

Pharmacotherapeutic group

Other hematological agents. ATX code: В06АВ.

Pharmacological properties

Pharmacodynamics

Deproteinized hemoderivative in the blood of calves causes an increase in the energy metabolism of cells, which is not organ-specific. This activity is confirmed by measurements of increased accumulation and increased utilization of glucose and oxygen. The total effect of these processes leads to an increase in ATP metabolism and, accordingly, to an increase in the energy supply of the cell. In deficient conditions with disruption of the normal functioning of energy metabolism (hypoxia, substrate deficiency) and in conditions with increased energy needs (repair, regeneration), Actovegin® activates energy-dependent processes of functional metabolism and conservation metabolism. As a secondary effect, an increase in blood supply is observed.

Pharmacokinetics

Using chemical analytical methods, it is impossible to study the pharmacokinetic parameters of the drug Actovegin®, such as absorption, distribution and excretion, since its active ingredients are physiological components that are normally present in the body. The study of various parameters in animal experiments and in clinical studies showed that the effect of the drug Actovegin® begins to appear no later than 30 minutes after use. The maximum effect after parenteral administration or oral administration is achieved after 3 hours (2–6 hours).

Indications for use

- metabolic and vascular disorders of the brain (including dementia); - peripheral (arterial and venous) vascular disorders and their consequences (arterial angiopathy, venous ulcers of the lower extremities), including diabetic polyneuropathy.

Directions for use and dosage

General dosing instructions Ampoules with a breaking point (TP) Instructions for using ampoules TR: Take the ampoule with the colored dot pointing up! Allow the solution to drain from the top of the ampoule by lightly tapping the ampoule and shaking it. Take the ampoule with the colored dot pointing upward! Break off the top of the ampoule as shown in the picture. The solution for injection has a slightly yellowish color. The color intensity of the drug from different batches may vary due to the raw materials used. Color does not affect the effectiveness and tolerability of the drug. Actovegin® solution for injection can be administered intravenously (IV), intramuscularly (IM) or intra-arterially (IA), and it can also be added to solutions for infusion. When administered as an infusion, 10-50 ml of the drug is added to 200-300 ml of the main solution (isotonic sodium chloride solution or 5% glucose solution). Infusion rate: approximately 2 ml/min. When prescribing by infusion, general contraindications to infusion therapy should be taken into account, such as decompensated heart failure, pulmonary edema, oliguria, anuria, overhydration. Dosage depending on specific indications Metabolic and vascular disorders of the brain: from 5 to 25 ml (200-1000 mg per day) intravenously daily for two weeks, followed by switching to tablet form. Metabolic and vascular disorders of the brain, such as ischemic stroke: 20-50 ml (800-2000 mg) in 200-300 ml of 0.9% sodium chloride solution or 5% dextrose solution, intravenously drip daily for 1 week, then 10-20 ml (400-800 mg) intravenously - 2 weeks, followed by switching to tablet form. Peripheral (arterial and venous) vascular disorders and their consequences: 20-30 ml (800-1000 mg) of the drug in 200 ml of 0.9% sodium chloride solution or 5% dextrose solution, intra-arterial or intravenous daily; Duration of treatment is 4 weeks. Venous ulcers of the lower extremities: 10 ml (400 mg) intravenously or 5 ml intramuscularly daily or 3-4 times a week depending on the healing process. Diabetic polyneuropathy: 50 ml (2000 mg) per day intravenously for 3 weeks, followed by switching to tablet form - 2-3 tablets 3 times a day for at least 4-5 months. The duration of treatment is determined individually according to the symptoms and severity of the disease.

Contraindications

Allergy to Actovegin® or similar drugs or excipients.

Precautionary measures

When administering Actovegin® parenterally, it is necessary to maintain sterility during manipulations. Actovegin® is intended for single use, since it does not contain preservative additives. Opened ampoules and the prepared solution should be used immediately. Unused drug and used consumables must be disposed of in accordance with local legislation. When mixing the contents of Actovegin® ampoules with other solutions for injection or infusion, physicochemical incompatibility, as well as interaction between active substances, cannot be ruled out, even if the solution remains clear. As a result, it is unacceptable to mix Actovegin® with other drugs, except for those mentioned in the “General dosing instructions” section. When using Actovegin® intramuscularly, no more than 5 ml should be administered slowly, since the solution is hypertonic. Parenteral administration of Actovegin® should be carried out under medical supervision if appropriate means are available for the treatment of allergic reactions. Due to the possibility of anaphylactic reactions, it is recommended that a test infusion/injection (hypersensitivity test) be performed before starting therapy. Do not use a solution that is cloudy or has visible solids. It is a source of sodium, which should be taken into account when prescribing to patients on a controlled sodium diet. If electrolyte disturbances (such as hyperchloremia and hypernatremia) are present, they should be adequately corrected.

Interaction with other drugs

Not known.

Use during pregnancy and breastfeeding

Use during pregnancy During pregnancy, Actovegin® should be used only if the therapeutic benefit outweighs the potential risk to the fetus. Use during breastfeeding During breastfeeding, Actovegin® should be used only if the therapeutic benefit outweighs the potential risk to the child.

Side effect

In the information below, adverse effects are rated according to the following frequency classification: Very common ≥ 1/10 Frequent ≥ 1/100 to

Overdose

There is no information regarding an overdose of Actovegin®. Based on available pharmacological data, no additional undesirable effects are expected.

Impact on the ability to drive vehicles and machinery

There is little or no impact.

Release form

Solution for injection 40 mg/ml. 2, 5 or 10 ml of the drug in colorless glass ampoules (type I, Eur. Pharm.) with a breaking point. 5 ampoules in a plastic blister pack. 1 (for 5 ml and 10 ml) or 5 (for 2 ml) blister packs with instructions for use are placed in a cardboard box. Transparent round protective stickers with holographic inscriptions and first-opening control are glued to the pack.

Storage conditions

Store in a place protected from light at a temperature not exceeding 25 °C. Keep out of the reach of children!

Shelf life

3 years. Do not use the drug after the expiration date.

Vacation conditions

By doctor's prescription.

Buy Actovegin injection solution 40mg/1ml in 2ml ampoules No. 5x5 in the pharmacy

Price for Actovegin solution for injection 40 mg/1 ml in 2 ml ampoules No. 5x5

Instructions for use for Actovegin injection solution 40 mg/1 ml in 2 ml ampoules No. 5x5

Contraindications and negative reactions of the body

The main contraindication for the use of Actovegin ointment, the instructions for use warn about this, is hypersensitivity to the components of the drug. Due to individual intolerance to the drug, local allergic reactions may occur. To check the body's reactions, before using the ointment, apply a small amount to the inside of the wrist. If after a couple of hours there is no redness of the skin or discomfort, Actovegin ointment can be used.

Due to the natural composition of the product, there is no categorical ban on its use during pregnancy and lactation. But at the same time, you should use the ointment only if there are indications and recommendations from a doctor.

In practice, Actovegin ointment was well tolerated. Only with hypersensitivity are local allergic reactions possible. In this case, the use of ointment should be abandoned. To eliminate side effects, it is recommended to take antihistamines.

What it is

These are drugs that improve performance, memory and learning ability. Piracetam was created first - it appeared in the sixties of the last century. In the seventies, scientist Corneliu Giurgia discovered that this medicine stabilizes the membranes of cells in the central nervous system, improving the functioning of brain cells. They didn’t know the exact mechanism of how piracetam works—they were just guessing. Giurja proposed using it to restore mental abilities after injuries, oxygen starvation of the brain, with senile dementia and congenital dementia in children.

Most nootropics are of animal origin. They are extracted from the brains of pigs and cattle, rich in low molecular weight proteins. The drugs are inexpensive and rarely cause side effects, which is why doctors love them.

Indications, contraindications and adverse reactions during treatment with Actovegin

The medication in tablets is recommended for use in patients with certain diseases:

• in complex therapy of metabolic and vascular disorders associated with dementia, ischemic stroke, circulatory failure, and head injury;
• diabetic polyneuropathy, trophic ulcers, angiopathy.

Injection solutions and droppers with Actovegin are prescribed for similar diseases and conditions as for tablets.

Direct contraindications for therapeutic procedures are:

• pulmonary edema;
• fluid retention in tissues;
• decreased daily urine production, anuria;
• individual allergic reactions to the component composition;
• heart failure in the decompensation phase.

Actovegin rarely causes adverse reactions and is well tolerated by most patients. Sometimes during treatment the following is recorded:

• swelling, urticaria, fever, sweating, hot flashes and other allergy symptoms;
• nausea with vomiting, dyspepsia, epigastric pain, stool disorders;
• state of weakness, cephalalgia, attacks of dizziness, short-term fainting, involuntary trembling of the body, decreased blood pressure or hypertensive symptoms;
• painful sensations in the chest area, paleness of the skin, shortness of breath, rapid heartbeat;
• rapid breathing, problems with swallowing, discomfort in the throat and chest, feeling of suffocation;
• pain in the lumbar area, joints and bones.

If adverse reactions to treatment occur, it is necessary to consult your doctor and replace Actovegin with an analogue.

Possibilities of the drug Actovegin in the prevention and treatment of dementia

P

Dementia is understood as a diffuse impairment of mental functions as a result of organic brain damage, manifested by primary disorders of thinking and memory and secondary emotional and behavioral disorders. Dementia is an extreme degree of decline in higher mental functions. It is customary to talk about dementia in cases where impairments in memory and other cognitive functions are so pronounced that they interfere with the implementation of professional and social activities in the same volume and quality. If a person has impairments in memory, thinking or other higher mental functions, but they do not interfere with professional activities and/or do not cause maladaptation of the patient in everyday life, they speak of cognitive impairment (cognitive decline).

There are several types of dementia:

Alzheimer's disease, vascular dementia ("subcortical" dementia, subcortical arteriosclerotic encephalopathy), mixed dementia, alcoholic dementia, etc. Dementia is especially common in the elderly. According to population studies, it is detected in 5–20% of people over 60 years of age. According to a number of authors, the presence of dementia increases the mortality rate of elderly patients by almost 3 times. It is believed that this is due to mnestic-intellectual decline, so patients with dementia cannot adequately assess the severity of their disease and the need for treatment. In addition, due to memory loss (the main diagnostic criterion for dementia), such patients forget to take medications.

Alzheimer's disease and vascular dementia are the most common types of dementia

. In Russia, vascular dementia ranks first in frequency (5.4%), its share is from 10 to 39% of all cases of dementia. According to the ICD-10 definition, vascular dementia is the result of cerebral infarctions due to cerebral vascular disease, including cerebrovascular disease due to arterial hypertension (AH). Heart attacks are usually small, but their cumulative effect is manifested.

The development of vascular dementia is promoted mainly by ischemic brain lesions, both focal and diffuse, and clinically this can be characterized by a progressive deterioration of cognitive functions (memory, thinking, attention, orientation, etc.) and social skills. “Subcortical” dementia is characterized primarily by an increase in the time that the patient spends on performing mnestic-intellectual tasks. There is a decrease in concentration, rapid exhaustion, memory impairment, especially for current events, emotional and behavioral disorders. Memory loss is a characteristic symptom of “subcortical” dementias. However, mnestic disorders, as a rule, are more mildly expressed in comparison with the dementia that develops in Alzheimer's disease. There is no clinically clear amnesia for current or distant events. Memory impairments manifest themselves mainly during learning: it is difficult to memorize words, visual information, and acquire new motor skills. Basically, active reproduction of material suffers, while simpler recognition is relatively intact. External stimulation in the form of assistance with memorization, the establishment of semantic connections during information processing, and repeated presentation of material increase the productivity of memorization. The mnestic defect in subcortical dementias is localized at the stage of “working memory”: a decrease in the volume of information assimilation after the first presentations is noted.

The main pathogenetic role in the formation of mnestic disorders in subcortical dementias is played by dysfunction of the frontal lobes of the brain, which leads to decreased activity, lack of planning, and disruption of the sequence and selectivity of mnestic operations. Patients with vascular dementia are characterized by a slowdown in all mental processes and a narrowing of their range of interests. In later stages, impairments in abstract thinking and judgment may develop. As a rule, focal disorders of higher cortical functions (aphasia, agraphia, alexia, apraxia, acalculia) do not develop, which is typical for cognitive disorders of the subcortical type. The appearance of such severe symptoms accompanies severe dementia.

More than half of patients with vascular dementia experience so-called emotional incontinence (weakness of spirit, violent crying). Vascular dementia is characterized by long periods of stabilization and even a certain reverse development of mnestic-intellectual disorders, and therefore the degree of its severity often fluctuates quite significantly in one direction or another. In such cases, fluctuations in the state of regional cerebral blood flow are important.

In addition to cognitive impairment, patients with vascular dementia also have neurological manifestations: subcortical, pseudobulbar, cerebellar syndromes, impaired control of pelvic functions, mainly urinary incontinence, paresis of the muscles of the limbs, often mild and usually not affecting the functional activity of the patient. The combination of cognitive and marked neurological disorders distinguishes vascular dementia from degenerative diseases, in particular Alzheimer's disease, in which cognitive disorders and symptoms of impairment of higher cortical functions (aphasia, apraxia) dominate.

The leading role in the formation of dementia with vascular lesions of the brain is played by damage to the white matter of the brain and the basal ganglia, which leads to disruption of the connection between the frontal lobes of the brain and subcortical structures (the phenomenon of cortical-subcortical disconnection). The main pathogenetic factor in the development of this phenomenon is hypertension, which leads to changes in the vascular wall (lipohyalinosis), mainly in the vessels of the microvasculature. As a result, arteriolosclerosis develops, which causes a change in the physiological reactivity of blood vessels. Under such conditions, a decrease in blood pressure (BP), including due to inadequate antihypertensive therapy, leads to a decrease in perfusion and the development of ischemia of the white matter of the brain.

On T2-weighted images of magnetic resonance imaging of the brain, a marker of the presence of chronic ischemia is a rarefaction of the periventricular or subcortical white matter - leukoaraiosis (“glow of the white matter”), which is visualized. Morphologically, these zones represent a zone of demyelination, gliosis and expansion of perivascular spaces.

Based on the above, prevention and treatment

vascular dementia and cognitive impairment should primarily include adequate correction of high blood pressure. Achieving target blood pressure is mandatory, but the pace of its achievement should be as gentle as possible. They depend on the initial values ​​of blood pressure in a given patient, the duration and severity of both hypertension and concomitant diseases. But in general, the rule is true - a sharp decrease in blood pressure for an elderly patient with hypertension is no less, but rather more dangerous than its sharp increase. Treatment of hypertension, coronary heart disease, heart failure, prescription of antiplatelet agents, surgical correction of atherosclerotic narrowing of the great arteries help prevent the increase in cognitive impairment and, according to some data, reduce existing ones. Control of hyperglycemia and hyperlipidemia is also necessary. However, in a number of cases, pathogenetic therapy for dementia still seems impossible, since its cause remains either unknown (senile dementia of the Alzheimer's type) or cannot be affected (multi-infarct dementia).

Current approaches to the treatment of dementia are also based on improving the delivery and use of oxygen and glucose. Glucose and oxygen are necessary for brain cells to carry out aerobic glycolysis, during which 38 ATP molecules are produced, which, in turn, provide the cells with an adequate level of functioning. The importance of oxygen and glucose for maintaining the normal functioning of brain cells is evidenced by the fact that for the functioning of the brain (the weight of which is 2% of body weight), 50% oxygen and 10% glucose are extracted from the flowing blood at a normal volume of total blood flow. Indeed, in conditions of deficiency of these substances, the processes of not aerobic, but anaerobic glycolysis occur, as a result of which only 2 ATP molecules are formed. Under such conditions, not only is the normal functioning of brain cells impossible, but they also die.

Therefore, there are other areas for the prevention and treatment of dementia. Thus, for quite a long time in clinical practice, the drug Actovegin, a modern antihypoxant, has been used for this purpose. This is a highly purified hemodialysate obtained by ultrafiltration from the blood of calves. The drug contains organic low-molecular compounds: amino acids, oligopeptides, nucleosides; intermediate products of carbohydrate and fat metabolism; oligosaccharides and glycolipids, as well as electrolytes (sodium, calcium, phosphorus, magnesium) (Fig. 1). The technology for obtaining hemodialysate excludes the presence of protein and other components with antigenic and pyrogenic properties.

Rice.
1. Composition of the drug Actovegin The basis of the pharmacological action of Actovegin is its effect on the processes of intracellular metabolism
. Under the influence of this drug, the transport of glucose into cells and the absorption of oxygen in tissues improves. The entry of a large amount of oxygen into the cell leads to the activation of aerobic oxidation processes, which increases the energy potential of the cell (Fig. 2). Under the influence of Actovegin, glucose transporters are activated, and an increase in glucose transport is noted up to 50% of the maximum effect of insulin. But this action of Actovegin is insulin-independent: due to the presence of glycolipids in its composition, Actovegin directly causes the activation of glucose transporters.

Rice. 2. Pharmacological effect of Actovegin on the processes of intracellular metabolism

There are a large number of studies, both domestic and foreign, that indicate an improvement in cognitive processes during treatment with Actovegin. However, of particular interest, of course, are the results of double-blind, placebo-controlled studies (Fig. 3). The results of these studies indicate that patients with various brain diseases during treatment with Actovegin showed a significant improvement in cognitive functions compared to placebo.

Rice. 3. Results of double-blind, placebo-controlled studies of the drug Actovegin

Thus, B. Saletu et al., using IV Actovegin, found a significant improvement in memory, attention and some parameters of thinking in patients with age-related memory decline compared to placebo. This study included patients aged 50 to 80 years (mean age 64 years) with age-related memory decline, and none of the patients met diagnostic criteria for dementia. The authors noted this effect of Actovegin after 14 days of treatment.

Another group of researchers (WM Herrmann et al.) also used the IV route of administration of Actovegin. However, they examined patients with Alzheimer's disease and multi-infarct dementia (Fig. 5). Therefore, the period of treatment with Actovegin was already 4 weeks. In the Actovegin group, the authors found a significant improvement in cognitive processes for collecting and processing information, severity of dementia symptoms, patients’ general well-being and care needs compared to placebo. Moreover, improvement was noted after the second week of therapy and was even more pronounced after four weeks. Despite the fact that the chosen treatment period was relatively short (at least three months are needed), the required and significant effect was still revealed. This may be due to intravenous use of the drug, which could cause a faster onset of effect.

Rice. 5. Data from a survey of patients with Alzheimer’s disease and multi-infarct dementia after a course of Actovegin (iv)

The literature contains data from double-blind, placebo-controlled studies on the effectiveness of the oral dosage form of Actovegin. Thus, WD Oswald et al. showed that Actovegin increased the speed of cognitive processes in patients with mild to moderate organic brain damage syndrome to a significantly greater extent compared to placebo (Fig. 4). In this study, patients over 60 years of age with mild to moderate psychoorganic syndrome received 400 mg x 3 times or placebo for 8 weeks.

Rice. 4. Data from double-blind, placebo-controlled studies of the oral dosage form of Actovegin

W. Jansen and GW Brueckner studied the therapeutic effects of Actovegin forte tablets (200 mg of active substance) and the dependence of the results of therapy on the dose of the drug in elderly (60–72 years) patients with cerebrovascular insufficiency. Patients were randomized into 3 groups: Actovegin forte 3 tablets 3 times a day (40 people), Actovegin Forte 2 tablets 3 times a day (40 people), placebo (20 patients 3 tablets 3 times a day, 20 patients 2 tablets 3 times a day). The duration of therapy was longer than in the study by WD Oswald et al. and amounted to 12 weeks.

To assess intelligence, a jigsaw test was chosen (it is necessary to sort 16 decks in 7 patterns within a certain time), which requires synthetic and analytical abilities and is considered especially difficult for patients with reduced intelligence and the elderly (Fig. 6). This test also characterizes the degree of age-related decline in intellectual abilities. The authors found that both Actovegin dosage regimens improved thinking and attention in elderly patients to a significantly greater extent than placebo.

Rice. 6. Results of a mosaic test to assess intelligence in the elderly when taking Actovegin according to the regimen

HV Semlitsch et al. In a double-blind, placebo-controlled study, the effect of Actovegin on the so-called P300 component of evoked brain potentials in patients with age-related memory disorders was studied. The late positive component (P300) of potentials (syn.: cognitive evoked potentials) is used in studies of cognitive processes and nootropic drugs, since a close connection has been established between P300 and cognitive functions. This means that a potential nootropic drug should shorten P300 latency and/or increase P300 amplitude, and/or increase the activity of P300 sources.

Each patient in this study received therapy for 2 weeks with either 250 ml of a 20% Actovegin solution or 250 ml of placebo. After using Actovegin, the amplitude of parietal P300 increased in comparison with placebo. This may reflect improved cognitive processes in the parietal cortex, a region that plays a fundamental role in attention but is functionally damaged in dementia.

The results of EEG brain mapping showed that Actovegin, in contrast to placebo, has a significant positive effect on human brain function (decrease in delta and theta activity and increase in slow beta activity adjacent to alpha, decrease in fast beta activity). Topographically, the encephalotropic effects of treatment with Actovegin were more pronounced in the parietal, fronto-central and temporo-occipital areas. At the same time, topographically, the greatest differences between Actovegin and placebo were also observed in the parietal and temporal regions. These data are of interest because in recent studies with EEG brain mapping in Alzheimer's type dementia, it was the parietal and temporal regions that differed from those in the control group of healthy individuals. Indeed, most of the changes are described by neuropathologists, neurobiochemists and neuroradiologists in these areas of the brain. Significant decreases in cortical mass in the parietal and temporal regions have been described, consistent with decreased cerebral blood flow in the central and parieto-occipital regions and decreased glucose metabolism in these regions measured by positron emission tomography (PET) in the disease. Alzheimer's. RP Friedland et al. noticed that glucose metabolism suffers most in the temporo-parietal cortex. The author emphasizes that histopathological changes are most pronounced in this same area.

Thus, the results of double-blind, placebo-controlled studies indicate the effectiveness of the drug Actovegin for the prevention and treatment of dementia.

To prevent dementia in patients with impaired cognitive functions, Actovegin forte 200 mg x 3 times a day is usually used for 1.5–2 months. In patients with vascular dementia, they usually start with intravenous Actovegin 400-800 mg (10-20 ml) intravenously for 10-14 days, and then switch to oral Actovegin forte 200 mg 3 times a day.

An integrated approach to the treatment of elderly patients, including adequate treatment of cardiovascular diseases and the use of drugs with proven effectiveness, will improve the quality of life of elderly people, which is of great medical and social importance.
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5. Medvedev A.V. Vascular dementia // Modern psychiatry – 1998 – No. 4 – P.20–23.

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Do they have any effect?

Until the 2000s, the actual mechanism of action and effectiveness of nootropics was not particularly studied. Doctors prescribed them, and people drank them. There was a myth circulating among medical students that a month-long course of nootropics before exams improves memorization of the material, and to be sure, you need to inject it into a muscle or vein.

Now the proof of the drug’s effectiveness is not the doctor’s word, but research data. There must be at least three thousand participants, and they must be divided into at least two groups, one of which is a control group with a placebo. At the same time, neither the doctor nor the patient knows what each of the subjects is drinking - medicine or a “dummy”.

Nootropic drugs have been little studied, and studies of their effectiveness are inadequate. Either there are too few people, or the criteria are unclear. For example, they estimate the number of test points only after treatment - they apparently forgot before treatment. The American FDA, in principle, does not consider nootropics to be drugs - in the USA they are sold as dietary supplements.

“Everyone knows that nootropics are drugs without proven effectiveness. But they continue to be used, says Varvara Khaletskaya. — There are statistics, there are international protocols that help the doctor. But at the same time, each doctor’s personal experience remains with a wide range: from “they are useless” to “they are effective in many patients.”

The fact is that there is a rare exception: piracetam improves cognitive function in people with severe dementia, according to an assessment of 19 high-quality studies. But with a traumatic brain injury or mild dementia, piracetam will no longer help. Moreover, it is useless for healthy people who want to follow the path of Eddie Morra from the film “Dark Areas” and become a megabrain. Therefore, if biohacking experiments with Mexidol seem to be effective, it is only due to self-persuasion.