Cognitive impairment in adults and children. Impaired cognitive functions (memory, speech, perception) Impaired cognitive functions of the brain

Many people know that impaired blood circulation in the vessels of the neck and head is one of the main risk factors for the development of acute stroke, which has serious consequences for the health and life of patients. Meanwhile, much more often dyscirculatory problems cause changes that are not obvious at first glance: a progressive decrease in memory and the ability to concentrate, as well as other disorders of cognitive function.

Why cognitive impairments develop in vascular diseases of the brain, how they are manifested, diagnosed and treated: we will analyze in our review and the video in this article.

The brain began to cope with its work worse - perhaps this is a sign of illness

The essence of the problem

The most complex brain functions associated with:

• the process of rational cognition of the surrounding world;
• purposeful interaction with available objects, phenomena and living beings;
• perception (collection, receipt) of information;
• processing and analysis of the received data;
• memorization and storage in memory;
• exchange of information;
• construction and sequential execution of sequential actions, assessment of their results.

Thus, cognitive impairment is associated with a decrease in these functions relative to the initial level (individual norm).

Note! Each person has their own level of development of cognitive abilities, due to genetic characteristics. So, someone can boast of a phenomenal memory, while someone has difficulty memorizing a simple quatrain. There are no generally accepted norms for assessing cognitive function.

There are more than twenty pathologies accompanied by impaired cognitive functions. Vascular diseases occupy an important place among them.

Common causes of cognitive decline are:

• ischemic stroke (heart attack)the brain of certain localizations (see);
• multi-infarction condition;
• chronic ischemia of nerve tissues -discirculatory encephalopathy, vascular dementia;
• consequences of subarachnoid or intraventricular hemorrhage;
• dysmetabolic (mixed vascular-dysmetabolic) encephalopathy -hepatic, renal, hypoglycemic, etc.

Unfortunately, most chronic vascular diseases cause irreversible cognitive impairment. In some cases (for example, with successful treatment of acute cerebrovascular accident, correction of metabolic disorders), their full or partial recovery is possible.

What disorders are more common with CVD?

So, what cognitive impairment is provoked by a violation of the tone of the cerebral vessels? Depending on the severity, they are divided into light, medium and heavy.

Mild degree

An easy degree of impairment is characterized by the preservation of indicators of psychometric scales at the level of the average age norm. However, patients notice a decrease in the ability to remember, concentrate and analyze information and often show concern about this.

Note! Impairment of short-term memory and absent-mindedness are one of the first symptoms of chronic cerebrovascular diseases, which are accompanied by impaired cerebral vascular tone.

Despite the complaints of patients, mild cognitive disorders:

• invisible to others;
• do not cause difficulties in everyday life and at work;
• do not affect the quality of life of patients.

Moderate degree

Moderate disorders are accompanied by the appearance of complaints of high fatigue during mental stress, a pronounced decrease in memory, attention and learning ability.

With this form of cerebral circulatory insufficiency, signs of a disorder of cognitive function:

• are reflected in the patient's complaints;
• visible to others;
• hinder the performance of complex intellectual tasks.

Note! According to statistics, this form of pathology is determined in 12-17% of the elderly population of the world.

Severe degree

The severe degree of cognitive impairment, which was provoked by a violation of the vascular tone of the brain, is called vascular dementia. It occurs in 15-20% of all cases of cognitive decline, ranking three times after dementia in Alzheimer's disease and other degenerative diseases of the nervous system.

Dementia is an acquired mental disorder that is accompanied by a pronounced decrease in intelligence and complete social maladjustment of the patient.

The disease is accompanied by a complex disorder of cognitive functions, including:

• memory - the ability to perceive and reproduce the information received;
• attention;
• speech;
• gnosis - the ability to recognize objects by perception with the help of the senses;
• praxis - the ability to perform targeted movements;
• thinking;
• ability to plan;
• ability to make decisions;
• ability to control own labor and the actions of others.

Note! Unlike mental retardation, which manifests itself from birth, signs of dementia increase gradually, more often in old age.

It is manifested by a slowdown and rigidity of all mental processes. Patients experience difficulties even when performing simple everyday tasks (grocery shopping, cooking). Mnestic disorders are primarily expressed in a decrease in the ability to learn, later there is a violation of memory for past and current events.

More than 50% of patients are faced with emotional "incontinence" - weakness, tearfulness, irascibility. Many of them have clinical manifestations of depression.

In addition to cognitive disorders, the clinical picture of vascular dementia is often accompanied by the development of neurological deficits. The main syndromes of brain tissue damage are presented in the table below.

Table: Neurological syndromes in severe cognitive impairment:

In addition, paralysis and paresis of the limbs, impaired control of pelvic functions (urinary incontinence, fecal incontinence) are possible. Patients with vascular dementia often lose self-care skills and need constant care.

Methods for the diagnosis of cognitive impairment

Cognitive disorders are diagnosed by a neurologist.

The standard instruction is to use the following minimum survey scope:

1. Collection of complaints and anamnesis (from the words of the patient and relatives).
2. General neurological examination.
3. Neuropsychological testing.
4. Instrumental data (CT / MRI (see)).
5. Screening tests:

• "5 words";
• schulte test;
• clock drawing test;
• a short scale for assessing mental status.

Treatment principles

The main role in the correction of cognitive disorders in CVD is assigned to the elimination of vascular risk factors. All patients are advised to follow a rational diet, give up bad habits, and be physically active. Control of blood pressure, glucose and cholesterol concentration in the blood is of no small importance.

If cognitive impairment occurs after an acute cerebral stroke, the appointment is indicated:

• antiplatelet agents (Thrombo-Ass, Ticlopidine, Clopidogrel, Dipyridamole);
• indirect anticoagulants;
• antihypertensive drugs.

To improve cognitive functions, it is important to regularly train your memory by memorizing poetry and solving crosswords.

Additionally, medications can be prescribed:

• Piracetam;
• Galantamine;
• Donepizil;
• Vinpocetine;
• Gliatilin, etc.

The selection of a specific drug is determined by the severity and nature of cognitive impairment, the presence of concomitant pathologies, and the patient's tolerance of certain drugs.

With rare exceptions, cognitive impairment is a problem in old age. To avoid loss of memory, attention, learning ability and almost complete lack of independence in old age, it is important to lead a healthy lifestyle, eat right, be physically active and regularly exercise the brain.

Good results in the prevention of a decrease in cognitive functions are also obtained by timely treatment of circulatory disorders in the cerebral vessels.

Cognitive functions of the brain are the ability to understand, cognize, study, be aware, perceive and process (remember, transmit, use) external information. This is a function of the central nervous system - higher nervous activity, without which a person's personality is lost.

Gnosis is the perception of information and its processing, mnestic functions are memory, praxis and speech is the transmission of information. With a decrease in the indicated mnestico-intellectual functions (taking into account the initial level), one speaks of cognitive impairments, cognitive deficits.

A decrease in cognitive functions is possible with neurodegenerative diseases, vascular diseases, neuroinfections, severe traumatic brain injuries. In the mechanism of development, the main role is played by mechanisms that uncouple the connections of the cerebral cortex with subcortical structures.

The main risk factor is considered to be arterial hypertension, which triggers the mechanisms of vascular trophic disorders, atherosclerosis. Episodes of acute circulatory disorders (strokes, transient ischemic attacks, cerebral crises) contribute to the development of cognitive disorders.

There is a violation of neurotransmitter systems: degeneration of dopaminergic neurons with a decrease in the content of dopamine and its metabolites, the activity of noradrenergic neurons decreases, the process of excitotoxicity is started, that is, the death of neurons as a result of a violation of neurotransmitter relationships. The magnitude of the damage and the localization of the pathological process matter.

So, with the defeat of the left hemisphere, it is possible to develop apraxia, aphasia, agraphia (inability to write), acalculia (inability to count), alexia (inability to read), alphabetic agnosia (not recognizing letters), logic and analysis, mathematical abilities are violated, voluntary mental activity is inhibited ...

The defeat of the right hemisphere is manifested visually - spatial disturbances, the inability to consider the situation as a whole, the body scheme, orientation in space, the emotional coloring of events, the ability to fantasize, dream, compose are disturbed.

The frontal lobes of the brain play an important role in almost all cognitive processes - memory, attention, will, expressiveness of speech, abstract thinking, planning.

The temporal lobes provide the perception and processing of sounds, smells, visual images, the integration of data from all sensory analyzers, memorization, experience, and emotional perception of the world.

Damage to the parietal lobes of the brain gives a variety of variants of cognitive impairments - disorder of spatial orientation, alexia, apraxia (inability to perform targeted actions), agraphia, acalculia, disorientation - left - right.

The occipital lobes are the visual analyzer. Its functions are visual fields, color perception and recognition of faces, images, colors and the relationship of objects with a color scheme.

The defeat of the cerebellum causes cerebellar cognitive affective syndrome with dulling of the emotional sphere, disinhibited inappropriate behavior, speech impairments - a decrease in fluency of speech, the appearance of grammatical errors.

Causes of Cognitive Disorders

Cognitive impairments can be temporary, after traumatic brain injury, poisoning and recover in the interval from days to years, and can have a progressive course - with Alzheimer's disease, Parkinson's, vascular diseases.

Vascular diseases of the brain are the most common cause of cognitive impairment, varying in severity from minor impairments to vascular dementia. The first place in the development of cognitive impairments is occupied by arterial hypertension, then occlusive atherosclerotic lesions of the great vessels, their combination, aggravated by acute circulatory disorders - strokes, transient attacks, systemic circulatory disorders - arrhythmias, vascular malformations, angiopathies, impaired rheological properties of blood.

Metabolic disorders in hypothyroidism, diabetes mellitus, renal and hepatic failure, lack of vitamin B12, folic acid, alcoholism and drug addiction, abuse of antidepressants, neuroleptics, tranquilizers can cause the development of dysmetabolic cognitive disorders. With early detection and treatment, they can be reversible.

Therefore, if you yourself have noticed any emerging intellectual deviations, consult a doctor. The patient himself may not always realize that something is wrong with him. A person gradually loses the ability to think clearly, remember current events and at the same time clearly remembers old ones, intelligence, orientation in space decreases, the character changes to irritable, mental disorders are possible, self-service is disrupted. Relatives may be the first to notice any disturbances in daily behavior. In this case, bring the patient for examination.

Assessment for cognitive impairment

Baseline is considered to determine the presence of cognitive dysfunction. Both the patient and relatives are interviewed. The cases of dementia in the family, head injuries, alcohol use, episodes of depression, medications are important.

During examination, a neurologist can detect an underlying disease with corresponding neurological symptoms. The analysis of the mental state is carried out according to various tests, tentatively by a neurologist and in-depth by a psychiatrist. Mindfulness, reproduction, memory, mood, execution of instructions, imagery of thinking, writing, counting, reading are investigated.

The short scale MMSE (Mini-mental State Examination) is widely used - 30 questions for an approximate assessment of the state of cognitive functions - orientation in time, place, perception, memory, speech, performing a three-stage task, reading, sketching. MMSE is used to assess the dynamics of cognitive functions, the adequacy and effectiveness of therapy.

Slight decline in cognitive functions - 21 - 25 points, severe 0 - 10 points. 30 - 26 points is considered normal, but the initial level of education should be taken into account.

A more accurate clinical dementia rating scale (CDR) is based on the study of disorders of orientation, memory, interactions with others, behavior at home and at work, and self-care. On this scale, 0 points are normal, 1 point is mild dementia, 2 points are moderate dementia, 3 is severe dementia.

Scale - Frontal Dysfunction Battery is used to screen for dementia with predominant involvement of the frontal lobes or subcortical cerebral structures. This is a more complex technique and is determined by violations of thinking, analysis, generalization, choice, fluency, praxis, attention reaction. 0 points - severe dementia. 18 points - the highest cognitive ability.

The clock drawing test is a simple test when the patient is asked to draw a clock - a dial with numbers and arrows indicating a specific time can be used for the differential diagnosis of frontal dementia and lesions of subcortical structures from Alzheimer's.

For a patient with acquired cognitive deficit, a laboratory examination is necessary: \u200b\u200bblood test, lipid profile, determination of thyroid stimulating hormone, vitamin B 12, blood electrolytes, liver function tests, creatinine, nitrogen, urea, blood sugar.

For neuroimaging of brain damage, computer and magnetic resonance imaging, Doppler imaging of the great vessels, and electroencephalography are used.

The patient is examined for the presence of somatic diseases - hypertension, chronic lung diseases, heart.

A differential diagnosis of vascular dementia and Alzheimer's disease is carried out. Alzheimer's disease is characterized by a more gradual onset, gradual slow progression, minimal neurological impairment, late impairment of memory and executive functions, cortical type of dementia, absence of gait disorders, atrophy in the hippocampus and temporo-parietal cortex.

Treatment of disorders

Treatment of the underlying disease is mandatory!

For the treatment of dementia, donepezil, galantamine, rivastigmine, memantine (abixa, meme), nicergoline are used. Dosages, duration of admission and schemes are selected individually.

To improve cognitive functions, drugs of various pharmacological groups with neuroprotective properties are used - glycine, cerebrolysin, Semax, somazine, ceraxon, nootropil, piracetam, pramistar, memoplant, sermion, cavinton, mexidol, mildronate, solcoseryl, cortexin.
Treatment of hypercholesterolemia is mandatory. This helps to reduce the risk of developing cognitive dysfunction. This is adherence to a diet low in cholesterol - vegetables, fruits, seafood, low-fat dairy products; B vitamins; statins - liprimar, atorvastatin, simvatin, torvacard. Eliminate smoking, alcohol abuse.

Consultation with a neurologist on cognitive impairment

Question: is it useful to solve crosswords?
Answer: yes, this is a kind of "gymnastics" for the brain. You need to make your brain work - read, retell, memorize, write, draw ...

Question: is it possible to develop cognitive impairments in multiple sclerosis?
Answer: yes, the structure of the deficit of cognitive functions in multiple sclerosis is made up of impairments in the speed of information processing, mnestic impairments (short-term memory), impaired attention and thinking, visual-spatial impairments.

Question: what are “evoked cognitive potentials”?
Answer: The electrical response of the brain to the performance of a mental (cognitive) task. The neurophysiological method of evoked cognitive potentials is a recording of the bioelectric reactions of the brain in response to the performance of a mental task using electroencephalography.

Question: what drugs can you take on your own with mild distraction, impaired attention and memory after emotional overload?
Answer: dissolve glycine 2 tablets under the tongue or ginkgo-biloba preparations (memoplant, ginkofar) 1 tablet 3 times a day, vitamins of group B (neurovitan, milgamma) up to 1 month or nootropil - but then the doctor will prescribe the dosage depending on age and diseases. And it is better to see a doctor right away - you may underestimate the problem.

Neurologist S.V. Kobzeva

- a slight decrease in the patient's cognitive functions compared to a higher premorbid level. The symptoms remain objectively invisible, but the patients themselves complain of forgetfulness, difficulty concentrating, and rapid fatigue during mental work. Diagnostics involves pathopsychological and neuropsychological research of the intellectual sphere, a conversation with a psychiatrist, examination by a neurologist. Treatment is aimed at eliminating the cause of the cognitive impairment, includes psychocorrectional exercises, drug therapy, adherence to diet and daily regimen.

ICD-10

F06.7

General information

The word "cognitive" in translation from Latin means "cognitive, familiarizing". Thus, mild cognitive disorder (LCD) is a slight decrease in mental abilities: the ability to memorize and reproduce information, concentrate attention, solve abstract logical problems. LCR does not reach the level of mental retardation, dementia, or organic amnestic syndrome. Precedes, accompanies or occurs after an infectious or organic disease. The disorder is more susceptible to older people, among those over 65, the prevalence is 10%. Of this group, 10-15% develop symptoms of Alzheimer's disease during the year. LCR is more commonly diagnosed in people with a low level of education.

Causes of Mild Cognitive Disorder

Mild disorder of cognitive processes is not a separate nosological form, but a kind of condition that occupies an intermediate position between normal intellectual development and dementia. By origin, it is heterogeneous (polyetiological), the causes of development can be various pathological processes in the central nervous system:

• Neurodegenerative diseases. The disorder is formed with senile dementia of the Alzheimer's type, Parkinson's disease, Huntington's chorea, Lewy body dementia, and progressive supranuclear palsy. Cognitive decline precedes the onset of underlying symptoms.
• Vascular pathologies of the brain. LCR is diagnosed in patients with cerebral infarction, multi-infarction condition, chronic cerebral ischemia, hemorrhagic and combined vascular brain damage. Symptoms of cognitive impairment are found during illness and in sequelae.
• Dysmetabolic encephalopathy. Due to metabolic disorders, insufficiency of internal organs, disorders occur in the functioning of the central nervous system. LCR is determined in hypoxic, hepatic, renal, hypoglycemic, distyroid encephalopathy, deficiency of B vitamins and proteins, poisoning.
• Demyelinating diseases. The disorder is detected at an early stage of progressive paralysis, multiple sclerosis, and progressive multifocal leukoencephalopathy. It grows in accordance with the dynamics of the underlying disease.
• Neuroinfection. Deficiency of the cognitive sphere is determined at the initial stages of HIV-associated encephalopathy, Creutzfeldt-Jakob disease. In acute and subacute meningoencephalitis, PCR develops as a consequence of the infectious process.
• Traumatic brain injury. Mild cognitive impairment can be temporary or relatively persistent in the long-term period of traumatic injury. Symptoms are determined by the nature of the injury (depth, diffuseness, or localization of the lesion).
• Brain tumors. The disorder occurs early in the disease. The clinical picture is determined by the localization of the neoplasm.

Pathogenesis

The pathogenetic mechanisms of LCR are diverse, depending on the leading etiological factor. In old age, the processes associated with aging are influenced: weakening of attention, purposefulness, memory. Clinical and experimental psychological studies confirm that age-related deterioration of cognitive functions develops independently, without concomitant neuropsychiatric diseases against the background of natural aging processes of the central nervous system (age-related loss of neurons, changes in white matter nerve fibers and synaptic apparatus).

In 68% of cases, PCR occurs on the basis of cerebrovascular disorders, in which a decrease in the cognitive sphere is due to pathological changes in cerebral vessels, cerebral circulation insufficiency. In second place in terms of prevalence is degenerative damage to brain tissue (atrophy). Another 13-15% of elderly and senile patients have anxiety-depressive disorders and tend to exaggerate the severity of memory impairments.

Symptoms of Mild Cognitive Disorder

Clinical manifestations correspond to the state of cerebrasthenia: the patients are outwardly intact, there are no gross violations of criticism and intelligence, a slight attentive-mnestic decrease, rapid fatigue is determined. Patients complain of forgetfulness, absent-mindedness, difficulty in memorizing new material, the need to focus and hold attention. With vascular lung cognitive disorders in the onset, behavioral and emotional disturbances are observed - increased anxiety, affective instability, fussiness and distraction, mnestic symptoms appear later. In patients with degenerative CNS pathologies, memory problems first of all arise.

Patients often experience headaches, a feeling of heaviness in the head, general weakness, drowsiness, and dizziness. Ailments are of a non-systemic nature, during the day they have different intensities, in many patients they are noted in the morning and evening. Possible instability when walking, anxious and interrupted sleep, insomnia, lack of appetite, nausea. The condition worsens after mental and physical exertion. The course of PCR depends on the underlying disease, it can be fluctuating (often with cerebrovascular shifts), progressive, turning into dementia (with atrophic processes, tumors, some infections) and regressive (after a stroke, TBI, acute passing infections).

Complications

Mild and progressive cognitive impairment quickly leads to dementia if left untreated. Patients lose the ability to solve everyday tasks, they need help with self-care. Socialization is impaired - the circle of contacts is narrowed, patients cannot perform professional duties, attend social events. With a fluctuating course of the disorder, patients experience difficulties during the performance of intense mental tasks, but with the correct correction of the regimen and a decrease in stress, they retain their usual vital activity.

Diagnostics

LCR examination is performed by a neurologist, psychiatrist, clinical psychologist. For diagnosis, the criteria are used, determined taking into account the emphasis on memory loss, the normal or borderline general state of the cognitive sphere, the absence of dementia, oligophrenia and psychoorganic syndrome. Differentiation of PCR and these diseases is based on data from clinical and psychodiagnostic examination. The following methods are used:

• Conversation. The psychiatrist and neurologist interview the patient, finding out the history and the existing symptoms. Complaints of increased fatigue, difficulty in remembering and concentrating, and general confusion are characteristic. Patients whose professional activities are associated with high intellectual loads may note difficulties in formulating abstract ideas and logical conclusions.
• Psychological testing. Depending on the data of the anamnesis, the psychologist conducts a pathopsychological or neuropsychological examination. A slight degree of decrease in short-term memory, fluctuations in the dynamics of mental activity, a slight instability of attention are revealed. Reducing the abstract-logical function is possible, but not necessary. The test results are interpreted taking into account the patient's age, educational level and professional field.
• Neurological examination. An examination by a neurologist is prescribed for the purpose of differential diagnosis and establishing the causes of PCR. Often, mild but persistent neurological disorders are determined: anisoreflexia, discoordinating phenomena, oculomotor failure, symptoms of oral automatism. No distinct syndromes are found.

Treatment for mild cognitive impairment

Therapy is aimed at preventing dementia, slowing down the rate of cognitive decline, and eliminating existing mnestic disorders. The main therapeutic measures - etiotropic, pathogenetic - are aimed at the cause of the disorder. They can include the correction of dysmetabolic disorders, vascular changes, depression, the use of antioxidants, vasoactive, neurotransmitter, antiviral drugs, chemotherapy, surgical removal of the tumor. Common therapies are:

• Psychocorrection. To improve memory and attention, systematic exercises are used: reading and retelling texts, memorizing poems, words, pictures. Classes are held together with a psychologist and independently. At meetings with a specialist, new methods of memorization are mastered - the formation of semantic and situational connections, the analysis of situations and objects. The effectiveness of the exercises is monitored periodically, the set of exercises is adjusted.
• Medical treatment. The scheme of drug therapy is selected by the doctor individually. The most common drugs for the treatment of cognitive disorders are nootropics and metabolic agents.
• Correction of nutrition and daily regimen. Middle-aged and elderly patients need a diet low in fat and salt, with a sufficient intake of antioxidants. Moderate regular exercise, good sleep, rational alternation of physical and mental stress are important. After completing work, you need to remain socially active - attending hobby clubs, meeting friends, etc.

Forecast and prevention

With effective etiotropic treatment, the prognosis of LCR in most patients is favorable: the process of reducing cognitive abilities is suspended, the resulting disturbances are reduced (with a regressed course of the underlying pathology). The main prevention comes down to the prevention of vascular and atrophic processes in the brain. It is important to maintain physical activity, quit smoking and drinking alcohol, adjust nutrition, reducing the intake of fatty, smoked and salty foods, introduce a sufficient amount of vegetables, fruits, cereals, vegetable oils into the diet.

Moderate cognitive impairment refers to cognitive impairments that go beyond the age norm, although they do not reach a severe degree - dementia... Such disorders are noted in 11-17% of older people. Moderate cognitive impairment is intermediate between normal aging and severe dementia.

They are associated with:

Impairment of memory, attention or learning ability, confirmed by objective research (the patient himself or his relatives note the violation);

Maintaining full independence in everyday life - the listed disorders do not lead to any restrictions (this is the main difference between moderate cognitive disorders and dementia);
- the appearance of complaints of increased fatigue when performing mental work;
- a decrease in the results of neuropsychological tests compared to the average age norm (short scale for assessing mental status - MMSE, clock drawing test);
- absence of delirium and dementia (the result of a short scale for assessing mental status - at least 24 points);
- organic changes (associated with diseases of the brain, cardiovascular system, other organs).

The majority of patients with moderate cognitive impairment show impairment of several cognitive functions (thinking, attention, speech), but the leading is memory weakening (in 85% of patients).

Experts call mild cognitive impairment not a disease, but a syndrome. This means that their external manifestations can be caused by different reasons or their combination (age-related changes, neuronal death, vascular disorders, metabolic disorders). Therefore, when a syndrome of moderate cognitive disorders appears, it is necessary to undergo a thorough clinical, laboratory and instrumental examination in order to identify the possible cause of the impairment.

In about half of patients with complaints of memory loss, the use of medical tests does not confirm the presence of cognitive impairment. Emotional disorders are the most common cause of subjective complaints in the absence of objective evidence.in the form of increased anxiety or decreased mood, including depression. Often, cognitive deficits are caused by endocrine diseases (diabetes mellitus, hypothyroidism), heart or respiratory failure, certain systemic or infectious diseases... Of course, in this case, treatment should be directed not at the cognitive disorders themselves, but at eliminating these factors. In addition, it is important to exclude the association of mild cognitive impairment with side effects of drugs (these primarily include sedatives and anticholinergics) and, if such a connection is found, decide whether they can be canceled or replaced.

The most ambitious domestic research on moderate cognitive disorders was organized by the Department of Nervous Diseases of the First Moscow Medical University. I.M.Sechenov. It was carried out in 30 regions of the Russian Federation by 132 neurologists and covered more than three thousand patients (in each participating center, 25 first-time patients over 60 years of age were evaluated). The study included two stages: at the first stage, the patients assessed their own memory state, at the second stage (in the presence of complaints), standard neuropsychological testing (MMSE scale and clock drawing test) was carried out.

It was found that among people over 60 years old, subjective complaints of memory disorders and mental fatigue are found in 83% of patients (for people over 80 years old, this figure is 90%). Objective confirmation (test results) of cognitive impairment of varying severity is obtained in 69% of patients.

According to the severity of the identified cognitive disorders, the subjects were divided as follows:

Dementia - 25%

Moderate to mild cognitive impairment – 44%,

Subjective complaints with normal performance of neuropsychological tests - 14%,
- absence of any disorders in the cognitive sphere - 17%.

In every third patient, moderate cognitive impairments remain stable for a very long time, and sometimes even subside. More often, however, mild cognitive impairment syndrome progresses. Up to 15% of cases of mild cognitive impairment transform into dementia within one year, and within five years, dementia develops in 60% of patients.

For this reason, dynamic monitoring of each patient and repeated clinical and psychological studies are necessary.

The main question for patients and their families is: "Is it possible for people with mild cognitive impairments to identify those who are most likely to develop dementia?" Today this has become fundamentally possible due to the emergence of a special neuroimaging method - positron emission tomography (see Chapter 2) using special tracers. However, it requires very expensive equipment, which prevents its widespread use in everyday practice.

The 4 main types of mild cognitive disorder syndrome are:

1. Monofunctional amnestic type - isolated memory impairment while maintaining other functions (usually considered as the initial manifestation of Alzheimer's type dementia).
2. Polyfunctional type with memory impairment - impairment of several cognitive functions, including memory (high probability of gradual transformation into Alzheimer's disease).
3. Polyfunctional type without memory impairment - affects several cognitive functions without memory impairment (accompanied by vascular lesions of the brain, diffuse Lewy body disease, Parkinson's disease).
4. Monofunctional non-amnestic type - impairment of one cognitive function: thinking, speech, orientation, etc. Speech impairments may be associated with the initial stage of primary progressive aphasia, impaired praxis - cortico-basal degeneration, visual gnosis - posterior cortical atrophy, visual-spatial functions - dementia with Lewy bodies.

V.V. Zakharov
Department of Nervous Diseases, Moscow Medical Academy THEM. Sechenov, Moscow

One of the most common neurological symptoms is cognitive impairment. Since cognitive functions are associated with the integrated activity of the brain as a whole, cognitive impairment naturally develops in a wide variety of focal and diffuse brain lesions. Cognitive impairments are especially common in old age. According to statistics, from 3 to 20% of people over 65 years old have severe cognitive impairment in the form of dementia. The incidence of milder cognitive disorders in the elderly is even higher and reaches, according to some data, from 40 to 80% depending on age. The current trend towards an increase in life expectancy and, accordingly, an increase in the number of elderly people in the population makes the problem of cognitive impairment extremely relevant for neurologists and doctors of other specialties.

Definition of cognitive functions
Cognitive functions are usually understood as the most complex functions of the brain, with the help of which the process of rational cognition of the world is carried out. Cognitive functions include memory, gnosis, speech, praxis, and intelligence.
Memory is the ability of the brain to assimilate, store and reproduce information necessary for current activity. Memory function is associated with the activity of the entire brain as a whole, but structures of the hippocampus circle are of particular importance for the process of memorizing current events. Expressed memory impairments for life events are usually denoted by the term "amnesia".
Gnosis is the function of perception of information, its processing and synthesis of elementary sensory sensations into holistic images. Primary disorders of gnosis (agnosia) develop in the pathology of the posterior parts of the cerebral cortex, namely the temporal, parietal and occipital lobes.
Speech is the ability to exchange information through utterances. Speech disorders (aphasia) most often develop with pathology of the frontal or temporo-parietal regions of the brain. In this case, the defeat of the temporoparietal divisions leads to all sorts of disorders of speech understanding, and with pathology of the frontal lobes, the ability to express one's thoughts with the help of speech statements is primarily impaired.
Praxis is the ability to acquire, maintain and use a variety of motor skills. Violations of praxis (apraxia) most often develop with pathology of the frontal or parietal lobes of the brain. In this case, the pathology of the frontal lobes leads to a violation of the ability to build a motor program, and the pathology of the parietal lobes leads to improper use of one's body in the process of a motor act with a preserved movement program.
Intelligence is understood as the ability to compare information, find similarities and differences, make judgments and inferences. Intellectual abilities are provided by the integrated activity of the brain as a whole.
Neuropsychological research methods are used to assess cognitive functions. They represent various tests and tests for memorizing and reproducing words and pictures, recognizing images, solving intellectual problems, studying movements, etc. A complete neuropsychological study allows you to identify the clinical features of cognitive impairment and make a topical diagnosis. However, in everyday clinical practice, it is not always possible to conduct a complete neuropsychological examination. Therefore, in outpatient practice around the world, the so-called neuropsychological screening scales are widely used, which make it possible to confirm the presence of cognitive disorders in general and evaluate them quantitatively. An example of such a screening scale is the short mental status scale, which is shown in the table.

Cognitive impairment syndromes
Focal brain damage leads to impairment of one or more cognitive functions, which are based on a single pathogenetic mechanism. This kind of cognitive impairment is characteristic of the consequences of a stroke, brain injury, or develops with a brain tumor. However, in the most common neurological diseases, brain damage is not limited to one focus, but is multifocal or diffuse. In such cases, impairment of several or all of the cognitive functions develops, and several pathogenetic mechanisms of the formation of impairments can be traced.
Cognitive impairments in multifocal or diffuse brain damage are usually classified according to the severity of the impairment. The most severe type of disorder of this kind is dementia. The diagnosis of dementia is appropriate if there is memory impairment and other cognitive impairments (at least one of the following: impairment of praxis, gnosis, speech, or intelligence) that are so severe that they directly affect daily life. The conditions for the diagnosis of dementia are also clear consciousness of the patient and the presence of an established organic brain disease, which is the cause of cognitive impairment.
Dementia is most common in old age, with Alzheimer's disease (AD) being the most common cause of dementia. AD is a degenerative brain disease associated with the progressive death of acetylcholinergic neurons. This disease usually begins after age 65. The first and main symptom of AD is progressive forgetfulness of life events. In the future, disorders of spatial orientation and speech are added to mnestic disorders. In advanced stages of asthma, patients' independence is lost, and there is a need for outside help.
In AD, those parts of the brain are selectively affected, which are in direct connection with cognitive processes. In contrast, the primary motor and sensory cortical fields remain relatively intact, at least in the stages of mild to moderate dementia, therefore AD is characterized by selective cognitive impairment. Focal neurological symptoms, such as paresis and paralysis, sensory disorders, impaired coordination of movements, are almost always absent. The presence of focal neurological symptoms in combination with mild or moderate dementia is evidence against the diagnosis of AD or indicates a combination of this disease with another pathology of the brain, most often vascular.
Cerebrovascular insufficiency is the second cause of dementia in old age after AD. In this case, the direct cause of brain damage is repeated strokes, chronic cerebral ischemia, or, most often, a combination of repeated acute disorders and chronic cerebrovascular accident. The clinical picture of vascular dementia differs significantly from AD, while memory impairments for life events are relatively not expressed, and intellectual disorders come to the forefront of the clinical picture. Patients experience difficulties in generalizing, identifying similarities and differences between concepts, a significant slowdown in thinking and a decrease in concentration of attention develop.
In contrast to AD, vascular dementia is almost always characterized by a combination of cognitive impairment and focal neurological symptoms, with the formation of a syndrome of discirculatory encephalopathy (DE). The most typical manifestations of DE are pseudobulbar syndrome, hypokinesia, increased muscle tone by the plastic type, asymmetric increase in tendon reflexes, gait disturbance, and pelvic disorders. The absence of these focal neurological disorders makes the diagnosis of vascular dementia highly doubtful.
Neuroimaging - computed tomography or magnetic resonance imaging of the brain - is of great importance in the differential diagnosis of asthma and vascular dementia. In AD, pathological changes during neuroimaging may be absent or represent cerebral atrophy, most pronounced in the hippocampus. In contrast, vascular dementia is characterized by significant changes in neuroimaging in the form of cerebral infarctions and diffuse rarefaction of white matter density (so-called leukoaraiosis).
AD and vascular dementia have common risk factors, such as old age, arterial hypertension and cerebral atherosclerosis, carriage of the APOE4 gene and some others; therefore, AD and cerebrovascular insufficiency very often coexist. Clinical and morphological comparisons indicate that almost half of AD cases have cerebral infarctions and leukoaraiosis. On the other hand, in 77% of elderly patients with lifetime AD diagnosis, morphological signs of a concomitant neurodegenerative process are revealed. In such cases, it is customary to talk about mixed (vascular-degenerative) etiology of dementia. Many authors suggest that the prevalence of mixed dementia is greater than the prevalence of "pure" AD or "pure" vascular dementia.
In addition to AD, vascular and mixed dementia, the causes of severe cognitive impairment can be other degenerative brain diseases, traumatic brain injury, brain tumors, impaired absorption of cerebrospinal fluid from the ventricles (the so-called resorptive hydrocephalus), neuroinfection, dysmetabolic disorders, etc. In the literature, several dozen nosological forms are mentioned that can lead to dementia. However, the prevalence of these diseases is incomparable with the prevalence of AD, vascular and mixed dementia. The last three indicated nosological forms are responsible, according to statistics, for 70-80% of dementia in old age.
Dementia is the most severe cognitive impairment. In the vast majority of cases, dementia develops gradually, while severe cognitive impairment is prevented by less severe disorders. In 1997, the American neurologist R. Petersen suggested using the term "mild cognitive impairment" (MCI) to denote cognitive impairments at the pre-dementia stages of organic brain damage. Moderate cognitive impairment (MCI) is a failure of one or more cognitive functions that go beyond the age norm, but do not limit daily activity, that is, do not cause dementia. MCI is a clinically defined syndrome. With it, cognitive disorders cause anxiety for the patient himself and attract the attention of others. The diagnosis of MCI is confirmed by the data of neuropsychological research methods, which reveal a more pronounced decrease in cognitive functions than acceptable for age. According to epidemiological data, MCI syndrome is observed in 10-15% of elderly people. The risk of developing dementia in this category of the elderly population significantly exceeds the average risk (10-15% per year compared to 1-2%). Long-term observations indicate that within five years, 55-70% of patients with MCI develop dementia. The causes of MCI syndrome are similar to those of dementia in old age. The most common cause of MCI is a neurodegenerative process, cerebrovascular insufficiency, or a combination of both.
According to our experience, along with dementia and MCI syndrome, it is advisable to single out also mild cognitive impairments (LCI), while cognitive disorders are minimally expressed and their objectification requires the use of very sensitive neuropsychological methods. Most often, LCI is manifested by a decrease in concentration and short-term memory impairment. Despite their minor severity, these cognitive impairments can cause anxiety for the patient and a decrease in the quality of life. In the pathogenesis of LCI in the elderly, age-related changes themselves play an important role. It is known that, on average, according to statistics, a person's cognitive abilities gradually decrease starting from the age of 20-30. In 1994, the World Psychogeriatric League proposed the use of a special diagnostic position - aging associated cognitive decline (AACD) - to denote mild, predominantly age-related cognitive impairment in the elderly. However, in practice, it is very difficult to distinguish between natural age-related cognitive decline and cognitive disorders associated with the earliest manifestations of vascular and degenerative diseases of the brain. Therefore, from our point of view, the term "mild cognitive impairment" is more correct.

Evaluation of patients with cognitive
violations
Complaints of decreased memory or decreased mental performance are the basis for a neuropsychological examination. Moreover, such complaints can come both from the patient himself and from his relatives or closest circle. The latter is a more reliable diagnostic sign, since the patient's self-assessment of the state of his cognitive functions is not always objective.
In routine clinical practice, neuropsychological research may be limited to simple screening scales, such as the Brief Mental Status Scale. Complicating the protocol of neuropsychological research is not always advisable. The use of complex tests, increasing the sensitivity of the method, leads to a decrease in the specificity of the results obtained, since their implementation largely depends on the age and level of education of the patient.
However, in about half of patients with active complaints of memory loss, the use of simple screening scales does not confirm the presence of cognitive impairment. The most common cause of subjective complaints of decreased memory in the absence of objective confirmation is emotional disorders in the form of increased anxiety or decreased mood background. Therefore, all patients with complaints of memory loss should carefully evaluate the emotional sphere. The likelihood of depression is especially high with complaints of memory loss in young or middle-aged people. Another reason for the lack of objective confirmation of cognitive impairment in active memory complaints is the lack of sensitivity of screening neuropsychological scales. Therefore, in addition to assessing and medication correction of the emotional state, in such cases, it is advisable to dynamically monitor the patient and repeat clinical and psychological studies with an interval of three to six months.
If there is objective evidence of cognitive impairment, an attempt should be made to establish their cause, i.e., the nosological diagnosis. It should be borne in mind that cognitive disorders are not always a manifestation of the primary brain disease. It is not uncommon for dementia or less severe disorders to occur as a result of systemic dysmetabolic disorders, which, in turn, are a complication of various endocrine or somatic diseases. Most often, cognitive disorders of a dysmetabolic nature are associated with hypothyroidism, liver or kidney disease, vitamin B12 or folic acid deficiency. Therefore, the identification of dementia or less severe cognitive impairments requires a comprehensive assessment of the patient's health status and treatment of concomitant somatic and endocrine diseases.
Optimization of ongoing drug therapy is also important. It should be remembered that many drugs, especially psychotropic drugs, have a negative effect on memory and other cognitive abilities. The most adverse effects on cognitive function are anticholinergics, tricyclic antidepressants, antipsychotics, and benzodiazepines. These drugs should be avoided if possible, especially in the elderly. Alcohol abuse is also unacceptable.
It is important to investigate not only the patient's somatic status, but also his emotional state. It has already been mentioned above that emotional disorders of the anxiety-depressive series can cause subjective cognitive disorders. However, severe depression can also cause objective cognitive impairment and even mimic dementia (so-called pseudodementia). If depression is suspected in an elderly person, the use of ex juvantibus antidepressants is acceptable, and antidepressants with a minimal anticholinergic effect, such as selective serotonin reuptake inhibitors, should be used.
The presence of cognitive impairment, of course, requires a study of the neurological status and a computerized X-ray or magnetic resonance imaging (MRI) of the brain. In general, the nosological diagnosis is based on the features of cognitive disorders, the nature of concomitant focal neurological symptoms and neuroimaging data. Thus, the predominance of memory disorders in the clinical picture, the absence of focal neurological symptoms and atrophy of the hippocampus on MRI are characteristic of AD. The relative preservation of memory for life events, pronounced neurological symptoms and cerebral infarctions on MRI indicate the vascular etiology of cognitive impairment. A combination of the above clinical signs may indicate mixed (vascular-degenerative) cognitive disorders. More rare causes of cognitive impairment have specific neuropsychological and neurological features that, in most cases, allow a correct diagnosis.

Cognitive impairment treatment
The choice of therapeutic tactics is determined by the severity of cognitive impairments and their etiology. For mild to moderate dementia associated with asthma, cerebrovascular insufficiency, or with mixed, vascular-degenerative etiology of dementia, the drugs of first choice are acetylcholinesterase inhibitors (galantamine, rivastigmine, donepilzin) and / or memantine. The use of these drugs has an undeniable positive effect on memory and other cognitive functions, contributes to the normalization of behavior, increases adaptation to everyday life and, in general, improves the quality of life of patients and their relatives. According to some reports, the use of these drugs also helps to reduce the rate of progression of cognitive impairment; however, this issue requires further study.
At the stage of moderate and mild cognitive impairment, the effectiveness of acetylcholinesterase and memantine inhibitors has not been proven to date. Since cognitive impairment does not significantly affect everyday life in MCI and LCI, the main goal of therapy for mild cognitive impairments is not so much memory improvement, but prevention of the progression of cognitive disorders, i.e. prevention of dementia. Therefore, drugs of first choice are drugs with neuroprotective effect. This effect is expected in so-called vascular and metabolic drugs.
Vascular drugs can be divided into three main pharmacological groups:
phosphodiesterase inhibitors: aminophylline, pentoxifylline, vinpocetine, ginkgo biloba preparations, etc. The vasodilating effect of these drugs is associated with an increase in the cAMP content in the smooth muscle cells of the vascular wall, which leads to their relaxation and an increase in the lumen of the vessels. At the same time, these drugs have an effect mainly on the vessels of the microvasculature and do not cause the stealing effect;
calcium channel blockers: cinnarizine, flunarizine, nimodipine, which have a vasodilating effect due to a decrease in the intracellular calcium content in the smooth muscle cells of the vascular wall. According to some reports, calcium channel blockers have the most pronounced effect on the vessels of the vertebrobasilar basin;
a2-adrenergic receptor blockers: nicergoline. This drug eliminates the vasoconstrictor effect of the mediators of the sympathetic nervous system: adrenaline and norepinephrine.
It is important to note that ischemia and hypoxia have pathogenetic significance not only in cerebrovascular insufficiency, but also in the neurodegenerative process. Therefore, the use of vascular drugs is justified not only in chronic cerebral ischemia, but also in the initial stages of AD. Many vascular drugs also have additional metabolic and antioxidant properties (eg, standardized ginkgo biloba extract).
GABAergic drugs (piracetam and its derivatives), peptidergic drugs and amino acids (cerebrolysin, Actovegin, glycine, Semax) and some metabolites (encephabol) have a beneficial effect on neurometabolic processes. Neurometabolic drugs have a nootropic effect, optimizing metabolic processes and increasing the plasticity of neurons in the brain. In experimental conditions, it has been repeatedly shown that neurometabolic drugs increase the survival of neurons under conditions of hypoxia or when simulating a neurodegenerative process. Therefore, the use of these drugs at the stage of LCI and MCI is absolutely justified.
A very promising drug of neurometabolic action is Actovegin, which is a highly purified deproteinized hemodialysate, which is obtained by ultrafiltration from the blood of calves. The drug contains low-molecular compounds weighing up to 5000 Daltons, such as biologically active amino acids, peptides, nucleosides and oligosaccharides, as well as a number of valuable trace elements, while the biochemical composition of Actovegin is strictly standardized.
In experimental models, it was shown that the biologically active components of Actovegin have a positive effect on intracellular metabolism. Under the influence of Actovegin, the transmembrane transport of glucose and oxygen increases, which leads to an increase in the survival of cell cultures under various adverse effects. In addition, a very important quality of Actovegin is its ability to activate antioxidant enzymes, primarily superoxide dismutase, and thus protect cells from damage by reactive oxygen species formed under hypoxic conditions.
The positive nootropic effect of the drug has been demonstrated in a series of clinical trials using a double-blind method. Thus, according to B. Saletu et al., Actovegin therapy contributes to a statistically and clinically significant decrease in the severity of mnestic and intellectual disorders in mild cognitive impairments of an age-related nature. The nootropic effect of Actovegin was also confirmed by electrophysiological research methods: during therapy with this drug, the optimization of the P300 cognitive evoked potential was recorded. Other researchers also testify to the positive effect of Actovegin in mild to moderate cognitive impairment of the vascular and degenerative nature.
According to randomized trials, Actovegin has a beneficial effect on cognitive function not only in patients with mild to moderate impairment, but also in dementia. Thus, in a series of studies, it was shown that against the background of Actovegin therapy, there is a positive dynamics of mnestic and other cognitive functions in patients with both BA and vascular dementia.
In everyday clinical practice, Actovegin has been successfully used for 35 years. The drug is safe to use and well tolerated. Side effects are rare and do not pose a threat to life and health. This can be a feeling of heat, dizziness, headache, gastrointestinal upset.
Thus, cognitive impairment is one of the most common neurological symptoms, especially in elderly patients. To identify cognitive disorders, it is necessary to use neuropsychological research methods. In everyday clinical practice, these can be simple screening scales, the application and interpretation of which does not require special psychological education or experience. Therapy for cognitive impairment depends on its severity and etiology. The most common causes of cognitive impairment in old age are cerebrovascular insufficiency and neurodegenerative processes, with acetylcholinesterase inhibitors and memantine having the greatest effect in the dementia stage. At the same time, at the stage of mild and moderate cognitive impairment, vascular and metabolic drugs with a neuroprotective effect are more appropriate.

Literature:
1. Damulin I.V. Dyscirculatory encephalopathy in old and senile age // Abstract of the thesis. diss ... doct. honey. sciences. M., 1997.
32 s.
2. Damulin I.V. Alzheimer's disease and vascular dementia / ed. N.N. Yakhno. M., 2002.85 p.
3. Zakharov V.V., Damulin I.V., Yakhno N.N. Drug therapy for dementia // Clinical Pharmacology and Therapy. 1994. T. 3. No. 4. S. 69-75.
4. Zakharov V.V., Yakhno N.N. Memory impairment. M .: GeotarMed. 2003.S. 150.
5. Luria A.R. Higher cortical functions of a person. M .: publishing house of Moscow State University. 1969.
6. Luria A.R. Fundamentals of Neuropsychology. M .: publishing house of Moscow State University. 1973.
7. International Statistical Classification of Diseases and Related Health Problems. Tenth revision (ICD-10). Geneva, WHO. 1995.
8. Herman V.M., Bon-Schlchevsky V.J., Kuntu G. Infusion therapy with Actovegin in patients with primary degenerative dementia of the Alzheimer's type and multi-infarction dementia (results of a prospective, placebo-controlled, double-blind study in patients undergoing hospital) // RMZh. 2002. T. 10.No. 15, pp. 658-663.
9. Shmyrev V.I., Ostroumova O.D., Bobrova T.A. Possibilities of the drug Actovegin in the prevention and treatment of dementia // BC. 2003. T. 11.No. 4. P. 216-220.
10. Jansen V., Bruckner G.V. Treatment of chronic cerebrovascular insufficiency using Actovegin-forte dragees (double-blind, placebo-controlled study) // BC. 2002. T. 10. No. 12-13. S. 543-546.
11. Yakhno N.N., V.V. Zakharov. Memory impairment in neurological practice // Neurological journal. 1997.Vol. 4.P. 4-9.
12. Yakhno NN, Lavrov A. Yu. Changes in the central nervous system during aging // Neurodegenerative diseases and aging (a guide for doctors) / ed. I.A. Zavalishina, N.N. Yakhno, S.I. Gavrilova. M., 2001.S. 242-261.
13. American Psychiatry Association. Diagnostic and Statistical Manual of Mental Disorders. 4th Ed. // Washington: American Psychiatry Association. 1994.
14. Barker W. W., Luis C. A., Kashuba A. et al. Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia, and hippocampal sclerosis in the State of Florida Brain Bank // Alzheimer Dis Assoc Disord. 2002. V.16. P. 203-212.
15. Blass J.B. Metabolic dementias // Aging of the brain and dementia. Aging. V.13. Ed. By L. Amaducci et al. N.Y .: Raven Press. 1980.
P. 261-170.
16. DeGroot M., Brecht M., Machicao F. Evidence for a factor protective against hypoxic parenchymal cell injury in a protein free blood extract // Res commun Cherm Pathol Pharmacol. 1990. V.68. P. 125-128.
17. Folstein M. F., S. E. Folstein, P. R. McHugh. Mini-Mental State: a practical guide for grading the mental state of patients for the clinician //
J Psych Res. 1975. V. 12. P. 189-198.
18. Fu C., Chute D. J., Farag E. S., Garakian J. et al. Comorbidity in dementia: an autopsy study // Arch Pathol Lab Med. 2004. Vol. 128.
No. 1. P. 32-38.
19. Golomb J., Kluger A., \u200b\u200bP. Garrard, Ferris S. Clinician's manual on mild cognitive impairment // London: Science Press Ltd. 2001. P. 56.
20. Herrsshaft H., Kunze U., Glein F. Die Wirkung von Actovegin anf die Gehinstaffwech sel des menschen // Med Welt. 1977. Bd. 28. S. 339-345.
21. Hulette C.M. Brain banking in the United States // J Neuropathol Exp Neurol. 2003. Vol. 62. N. 7. P. 715-722.
22. Hershey L.A., Olszewski W.A. Ischemic vascular dementia // In: Handbook of Demented Illnesses. Ed. by J.C. Morris. New York etc .: Marcel Dekker, Inc. 1994. P. 335-351.
23. Iqbal K., Winblad B., Nishimura T., Takeda M., Wisniewski (eds) H.M. Alzheimer's Disease: Biology, Diagnosis and Therapeutics John Willey and Sons Ltd. 1997.830 p.
24. Kanowsky S., Kinzler E., Lehman E. et al. Confirmed clinical efficacy of actovegin in elderly patients with organic brain syndrome // Pharmacopsychiat. 1995. V. 28. P. 125-133.
25. Larrabee G.J., Crook T. M. Estimated prevalence of age associated memory impairment derived from standardized tests of memory function // Int Psychogeriatr. 1994. V. 6. N.1. P. 95-104.
26. Levy R. Aging-associated cognitive decline // Int Psychogeriatr. 1994. V. 6. P. 63-68.
27. Lezak M.D. Neuropsychology assessment // N.Y. University Press. 1983. P. 768.
28. Lovenstone S., Gauthier S. Management of dementia // London: Martin Dunitz. 2001.
29. Oswald W.D., Steyer W., Oswald B., Kuntz G. Die verbesserung fluider kognitiver leistungen als imdikator fur die klinishe wirksamkeit einer nootropen substanz. Eine placebokontrollierte doppelblind studie mit Actovegin // Z. Gerontopsychol Psychiatric. 1991. Bd4. S. 209-220.
30. Oswald W.D., Steyer W., Oswald B., Kuntz G. Die verbesserung fluider kognitiver leistungen mit Actovegin-infusionen bei alterspatienten mit leichem bis millel schweren organisdom psychosyndrom // Z. Geronto-psychiatrie. 1992. Bd5. S. 251-266.
31. Petersen R.S., Smith G.E., Waring S.C. et al. Aging, memory and mild cognitive impairment // Int. Psychogeriatr. 1997. Vol. 9.P. 37-43.
32. Saletu B., Grunberger J., Linzmayer L. et al. EEG brain mapping and psychometry in age-associated memory impairment after acute and 2 weeks infusions with the hemoderivative Actovegin: double blind placebo controlled trials // Neuropsychobiol. 1990-91. V.24. P. 135-145.
33. Semlitsch H.V., Anderer P., Saletu B., Hochmayer I. Topographic mapping of cognitive event-related potentials in double blind placebo controlled study with the hemoderivative Actovegin in age-associated memory impairment // Neuropsychobiol. 1990/91. Vol. 24. P. 49-56.
34. VanCrevel. Clinical approach to dementia // In: Aging of the brain and Alzheimer's disease. Ed. By D. F. Swab et al. Progress in brain research. Vol. 70. Amsterdam etc: Elsevier. 1986. P. 3-13.