Chronic cerebrovascular insufficiency

Synonyms:

• encephalopathy,
• chronic cerebral ischemia,
• slowly progressive cerebrovascular accident,
• chronic ischemic brain disease,
• cerebrovascular insufficiency,
• vascular encephalopathy,
• atherosclerotic encephalopathy,
• hypertensive encephalopathy,
• atherosclerotic angioencephalopathy,
• vascular (atherosclerotic) parkinsonism,
• vascular (late) epilepsy,
• vascular dementia.

The most widely used term in domestic neurological practice is “dyscirculatory encephalopathy ,” which retains its meaning to this day.

Cerebrovascular insufficiency in the vertebrobasilar region

One of the common causes of dizziness is cerebral circulatory insufficiency in the vertebrobasilar circulation (VBB), which can occur in the form of chronic ischemia, transient cerebrovascular accidents or strokes.

Pathogenesis

The main causes of ischemic changes in this pathology are factors that limit blood flow into the vertebrobasilar system or promote excessive outflow from it to other vascular beds. The pathogenesis of cerebrovascular insufficiency in VBD can cover an extremely wide range of changes. Along with the pathology of the vessels of the vertebrobasilar system (stenosis and occlusion) due to atherosclerosis, extravasal factors are of great importance. For example, thrombosis of the vertebral artery is possible due to dissection of the artery due to whiplash or other neck injury, or inadequate manual manipulation of the cervical spine.

Other causes also include pathological tortuosity, congenital developmental disorders in the form of hypo- and aplasia of the vertebral artery, and Kimmerli's anomaly. If the latter is present, when turning the head, bending and compression of the vertebral artery occurs with its possible trauma.

Also, pathological conditions such as Klippel-Feil-Sprengel anomaly, nonfusion of the posterior arch of the atlas, saddle-shaped hyperplasia of the lateral masses of the atlas, underdevelopment of the articular processes of the cervical vertebrae, cervical ribs, “steal” syndrome ( subclavian-vertebral steal) and a number of others. In addition, blockage of blood vessels often occurs with a thrombus that has formed and migrated to the vertebral or basilar artery from the heart cavity.

It should be noted, however, that most of the listed factors are significant specifically for acute vascular catastrophe, manifested by dizziness - transient cerebrovascular accidents or strokes. Systemic dizziness (i.e., when a person has a feeling of falling, moving in space, which is accompanied by nausea and vomiting) with chronic cerebrovascular insufficiency never occurs, and non-systemic dizziness most often disguises anxiety, depression, orthostatic hypotension, metabolic disorders ( hypo-, hyperglycemia), drug dizziness, disturbances of attention, vision, etc., which require adequate diagnosis and treatment.

Clinical manifestations

The core of the clinical picture in transient disorders of cerebral circulation in the vertebrobasilar system are episodes of dizziness, often accompanied by nausea, vomiting, instability when walking and standing, noise, a feeling of fullness in the ears, autonomic disorders in the form of profuse sweating, tachycardia, pallor or, conversely, redness facial skin, lasting from several minutes to several hours. Hearing impairments (mostly decreased) and vision may also be observed (“spots” in front of the eyes, “blurred vision”, “blurred picture”). Extremely dramatic for patients are sudden falls without loss of consciousness (“drop attacks”, Unterharnscheidt syndrome), which are acute circulatory disorders in the reticular formation of the brain stem and usually occur with sudden turns or throwing back the head.

Strokes in the vertebrobasilar region are characterized by a rapid onset (no more than 5 minutes pass from the appearance of the first symptoms to their maximum development, usually less than 2 minutes), as well as the following neurological symptoms:

1. motor disorders: weakness, clumsiness of movements or paralysis of the limbs;
2. Sensory disorders: loss of sensation or paresthesia of the limbs and face;
3. visual impairment in the form of double vision, loss of visual fields;
4. imbalance, instability
5. impaired swallowing and speech clarity.

A special form of acute cerebrovascular accident in the VBB is a “bowhunter’s stroke”, associated with mechanical compression of the vertebral artery at the level of the cervical spine with extreme rotation of the head to the side.

Mechanical compression of the vertebral artery at the level of the cervical spine, which underlies the development of “archer” stroke.

The mechanism of development of such a stroke is explained by the tension of the artery when turning the head, accompanied by tearing of the intima of the vessel (dissection), especially in patients with pathological changes in the arteries.

Diagnostics

When diagnosing cerebrovascular insufficiency in the VBD, it is necessary to take into account that the symptoms of the disease are often nonspecific and may be the result of another neurological or other pathology, which requires careful collection of patient complaints, study of the medical history, physical and instrumental examinations to identify the main cause of its development. The leading role in the diagnosis of clinically significant changes in blood flow in the vertebrobasilar region is currently played by neuroimaging methods of studying the brain (MRI and CT), as well as Doppler ultrasound and duplex scanning with color flow, which allow non-invasive and relatively cheap assessment of the structure and patency of the vascular bed.

It is important to note that the differential diagnosis between vertigo caused by damage to the cerebellum and/or brain stem (central) and that arising from dysfunction of the vestibular apparatus or vestibular nerve (peripheral) is not always simple. On the one hand, very often such conditions as benign paroxysmal positional vertigo are mistaken for a stroke, at the same time, sometimes patients with acute vascular insufficiency in the VBB are mistakenly treated for “cervical osteochondrosis with vestibulopathic syndrome” by chiropractors and osteopaths with the development of corresponding complications .

Treatment

In the case of an acute neurological deficit (alternating syndromes, cerebellar insufficiency, “negative” scotomas, etc.), the patient should be urgently hospitalized in a regional vascular center or neurological department to exclude a stroke in the VBB. If it is confirmed, treatment is carried out in accordance with currently relevant guidelines and recommendations.

For dizziness due to chronic cerebral circulatory failure, the VBB focuses on drugs that improve cerebral circulation due to vasodilating and rheopositive effects (vinpocetine, cinnarizine, betahistine, etc.). Adequate correction of blood pressure and prevention of thrombus formation in various heart rhythm disorders are of great importance.

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Causes of chronic cerebrovascular insufficiency:

Basic:

• atherosclerosis;
• arterial hypertension.

Additional:

• heart disease with signs of chronic circulatory failure;
• heart rhythm disturbances;
• vascular abnormalities, hereditary angiopathy;
• venous pathology;
• vascular compression;
• arterial hypotension;
• cerebral amyloidosis;
• diabetes;
• vasculitis;
• blood diseases.

For adequate brain function, a high level of blood supply is required. The brain, whose mass is 2.0-2.5% of body weight, consumes 20% of the blood circulating in the body. The value of cerebral blood flow in the hemispheres is 50 ml per 100 grams per minute, glucose consumption is 30 µmol per 100 grams per minute, and in gray matter these values ​​are 3-4 times higher than in white matter. Under resting conditions, the brain's oxygen consumption is 4 ml per 100 grams per minute, which corresponds to 20% of the total oxygen entering the body. With age and in the presence of pathological changes, the amount of cerebral blood flow decreases, which plays a decisive role in the development and increase of chronic cerebral circulatory failure.

The presence of headaches, dizziness, memory loss, sleep disturbances, the appearance of noise in the head, ringing in the ears, blurred vision, general weakness, increased fatigue, decreased performance and emotional lability - these symptoms most often simply “inform” a person about fatigue. Only when the vascular genesis of the “asthenic syndrome” is confirmed and focal neurological symptoms are identified, a diagnosis of “dyscirculatory encephalopathy” is made.

The basis of the clinical picture of discirculatory encephalopathy is currently recognized as cognitive impairment . In case of chronic cerebrovascular accident, it should be noted that there is an inverse relationship between the presence of complaints, especially those reflecting the ability to cognitive activity (memory, attention), and the severity of chronic failure: the more cognitive functions suffer, the fewer complaints. In parallel, emotional disorders develop (emotional lability, inertia, lack of emotional response, loss of interests), various “motor disorders” (disorders of walking and balance).

Modern ideas about chronic cerebrovascular insufficiency

In turn, the prevalence of dementia is 5–10% among people over 60 years of age [3]. Based on the data presented, we can conclude that 0.5–2.5% of older people suffer from vascular dementia. The number of people with vascular cognitive disorders that do not reach the severity of dementia is presumably 2–3 times greater than the number of people suffering from vascular dementia [3, 4]. Thus, the prevalence of CNMK can reach up to 10% of people over 60 years of age.

In domestic neurological practice, several synonymous diagnostic formulations are used to designate CNM:

• dyscirculatory encephalopathy (DEP);
• chronic cerebral ischemia;
• hypertensive encephalopathy;
• chronic cerebrovascular insufficiency;
• chronic cerebrovascular insufficiency;
• chronic cerebrovascular disease;
• ischemic brain disease.

All of the above diagnostic formulations can be considered as synonyms that denote a clinical syndrome that develops with chronic progressive non-stroke brain damage. Such a significant variety of diagnostic formulations reflects the history of the study of CNM, the evolution of views on this problem and the current lack of a unified view on the pathogenetic mechanisms and clinic of CNM.

The term “dyscirculatory encephalopathy” was proposed in 1958 by outstanding Russian neurologists Professors G.E. Maksudov and V.M. Kogan [5]. This term has been proposed to understand chronic progressive diffuse brain damage as a result of chronic ischemia and hypoxia, which is manifested by progressive cognitive and other neurological disorders. In 1985, this term was included in the domestic classification of vascular diseases of the brain, adopted at the plenum of the All-Union Society of Neurologists (Fig. 1) [6].

Development of neuroimaging methods at the end of the 20th – beginning of the 21st centuries. forced us to subject a certain revision to the idea of ​​the pathogenetic mechanisms of development of the clinical syndrome of DEP. It has been shown that, along with chronic ischemia and hypoxia, which leads to the development of diffuse changes in the white matter (leukoaraiosis (LA)), a significant contribution to the development of DEP is also made by repeated acute cerebrovascular accidents without clinical stroke - the so-called “silent” infarctions. They develop asymptomatically or with minimal, erased or atypical symptoms, which do not allow recognition of a stroke. However, subsequent accumulation of brain damage as a result of repeated “silent” infarctions contributes to the further progression of DEP [7, 8].

In connection with new ideas about the mechanisms of formation of DEP in 2001, Academician of the Russian Academy of Sciences, Professor N.N. Yakhno proposed a new edition of the definition of DEP: “dyscirculatory encephalopathy is a syndrome of various etiologies, manifested by progressive neurological, neuropsychological and mental disorders, which develops as a result of repeated acute cerebrovascular accidents and/or chronic cerebral circulatory failure” [9]. The above definition clearly demonstrates the preference of the term “dyscirculatory encephalopathy (various pathogenetic mechanisms of vascular damage to the brain are allowed) over the term “chronic cerebral ischemia” (meaning the presence of one mechanism of brain damage).

Etiology and pathogenesis of DEP

DEP is not an independent disease, but a complication of various cardiovascular diseases. The list of causes of CNM repeats the list of causes of strokes (Table 1). In practice, most often CNMC develops as a result of long-term uncontrolled arterial hypertension, atherosclerosis of the cerebral arteries and atrial fibrillation with repeated microthromboembolism in the brain.

The common etiological factors determine the high comorbidity of DEP and strokes. Typically, patients with DEP have a history of stroke, and patients who have had a stroke also have DEP. In the presence of a history of stroke, the diagnosis of DEP is legitimate if the stroke cannot explain all of the patient’s symptoms and if another concomitant disease (for example, neurodegenerative) is excluded.

There are 3 main pathogenetic mechanisms for the formation of chronic progressive non-stroke vascular lesions of the brain in DEP [8–11]:

• repeated acute cerebrovascular accidents without clinical stroke (“silent” heart attacks or “silent” hemorrhages);
• LA;
• secondary cerebral atrophy.

As a rule, “silent” infarcts have a small volume, i.e., they belong to the category of lacunar infarcts (less than 10–15 mm in diameter). A single lacunar infarction may remain asymptomatic. However, with repeated lacunar infarctions (which is often observed in the absence of adequate treatment of arterial hypertension), the accumulation of brain damage leads to the formation of neurological symptoms. Moreover, this symptomatology will develop gradually – like a chronic vascular lesion of the brain [7, 8].

The nature of neurological symptoms in repeated lacunar infarctions is determined by their location. Due to the anatomical and physiological characteristics of the cerebral vascular system, lacunar infarctions are most often found in the subcortical basal ganglia, internal capsule, pons and cerebellum [7, 8].

Damage to the subcortical basal ganglia (striatum, thalamus) as a result of lacunar infarctions leads to secondary dysfunction of the frontal lobes of the brain. This is explained by the presence of a close functional connection between the frontal cortex and subcortical formations. Therefore, disruption of the interaction between these areas leads to secondary dysfunction of the frontal cortex. Clinical analysis of neurological and neuropsychological symptoms, which are observed in the initial stages of CNM, indisputably indicates its connection with dysfunction of the frontal lobes of the brain [8–11].

LA is commonly understood as changes in the density and anatomical structure of the white matter of the brain, which are very common in old age and are often associated with vascular diseases. In this case, blanching of certain areas of the white matter of the brain is determined macroscopically, and demyelination, gliosis and expansion of perivascular spaces (criblures) are determined microscopically [8, 10–13].

The pathogenetic mechanisms of the development of LA remain incompletely understood. It is assumed that endothelial dysfunction plays an important role in this, which leads to increased permeability of the microvascular wall. As a result, the blood-brain barrier is disrupted, blood plasma leaks into the brain parenchyma, and chronic edema of certain parts of the white matter (primarily periventricular) is formed, which over time can lead to secondary morphological changes. It is also believed that repeated episodes of transient local cerebral ischemia without the formation of cerebral infarction (the so-called “incomplete” infarctions) are of great importance for the occurrence of PA [8, 10–13].

LA leads to disruption of communication between various cortical, as well as between cortical and subcortical structures (disconnection phenomenon). As a result of disconnection, the frontal lobes of the brain suffer the most, which is associated with their physiological role. The fact is that the function of the anterior parts of the brain is to control cognitive activity and behavior. In the absence of communication with other parts of the brain, this function cannot be performed [10, 11].

Cerebral atrophy is a natural result of damage to white matter in chronic insufficiency of blood supply to the brain. It develops according to the mechanism of the so-called “Walerian degeneration”: separation of the frontal lobes from the rest of the brain leads to a decrease in the activity of neurons in the anterior parts of the brain. According to general physiological laws, in functionally inactive (and therefore “unnecessary” neurons) the process of genetically programmed death (apoptosis) is triggered, which leads to cerebral cortical atrophy. In this case, the maximum severity of the atrophic process is observed in the anterior parts of the brain. With neuroimaging, this is manifested by a disproportionate expansion of the subarachnoid spaces in this area [14, 15].

Clinical picture of DEP

The clinical picture of DEP is highly variable. However, in the vast majority of cases, the clinical picture is dominated by neurological, emotional and cognitive dysfunctions of the frontal lobes of the brain, which reflects the pathogenetic basis and localization of the pathological process in DEP. The most commonly observed are various combinations of cognitive impairment, depression and/or apathy, and disorders of postural stability, balance and gait [10, 11, 16, 17].

Traditionally, there are 3 stages of DEP [9]:

Stage I. It is characterized by so-called subjective neurological symptoms: headache, dizziness, noise in the ears or head, increased fatigue, sleep disturbance, forgetfulness. Objectively, “scattered” neurological symptoms are detected in the form of increased and/or asymmetry of tendon reflexes, mild incoordination, nystagmus, intention tremor, etc. It was previously assumed that the clinical symptoms at this stage are based on dysfunction of neurons as a result of chronic ischemia and hypoxia without formation structural defect. However, the development of neuroimaging methods has convincingly shown that in reality, structural changes precede dysfunction: for a sufficiently long time, vascular lesions of the brain can remain asymptomatic. Currently, there is a widespread idea that the subjective neurological symptoms of stage I DEP are based on emotional disorders associated with frontal dysfunction: the so-called vascular depression or emotional lability [17–20].

At stage II of DEP, subjective neurological symptoms lose their relevance, criticism decreases, and at the same time, more distinct objective neurological symptoms are formed. One or more of the following neurological syndromes may develop [9]:

• moderate cognitive impairment (Table 2);
• pseudobulbar;
• gait and balance disorders (frontal dysbasia);
• amyostatic;
• pyramidal

At stage III of DEP, a combination of several of the above neurological syndromes is observed, cognitive impairment reaches the severity of dementia, and pelvic disorders are added [2, 9].

Diagnosis and differential diagnosis of DEP

To diagnose DEP syndrome, the presence of cognitive impairment and other characteristic neurological symptoms, underlying vascular disease, and evidence of a cause-and-effect relationship between the vascular disease and CNS damage are required (Table 3).

One of the significant evidence of the vascular nature of brain damage is the characteristic features of cognitive status. With DEP, at least in its initial stages, memory impairments are absent or present to a small extent. Violations of frontal control functions come to the fore in the structure of cognitive disorders in the form of decreased mental activity, impaired planning, cognitive inertia and lack of control [16, 22, 23]. To identify these disorders, specific “frontal” neuropsychological tests should be used. In particular, “frontal” tests are included in the Montreal Cognitive Impairment Scale (Moka Test). The international scientific community currently recommends their use for screening for non-dementia vascular cognitive disorders [24].

A challenging but pressing clinical challenge is the differential diagnosis between vascular and primary degenerative cognitive disorders, since DEP and neurodegenerative processes are the most common causes of cognitive impairment in older people. The differential diagnosis is based on an analysis of neuropsychological characteristics and neurological symptoms. As mentioned above, in DEP, disturbances of “frontal” executive functions predominate, while in the neurodegenerative process, memory impairments predominate. The neurological status of DEP reveals pseudobulbar, amyostatic syndromes, balance and gait disorders. In primary degenerative cognitive disorders, focal neurological symptoms are absent until the stage of severe dementia [2, 9, 17, 22, 23].

For the differential diagnosis of DEP and the neurodegenerative process, as well as the identification of combined forms, the modified Khachinsky scale is used (Table 4) [25].

Reliable verification of the diagnosis of DEP is neuroimaging - computed tomography, x-ray or, preferably, magnetic resonance imaging. This research method makes it possible to visualize the consequences of acute disorders of the brain and PA [10, 11]. The presence of these changes is indisputable evidence of vascular damage to the brain. However, even in the presence of proven vascular cerebral damage, clinical symptoms can be caused by various reasons. Thus, at least 15% of dementia in old age belongs to the so-called “mixed” dementia, when cerebrovascular insufficiency is combined with Alzheimer’s disease. Such a frequent combination of vascular and degenerative brain damage is explained by common risk factors and pathogenetic mechanisms [26].

Treatment of DEP

DEP is not an independent nosological form. This is a polyetiological syndrome that can complicate the course of various cardiovascular diseases, for example, arterial hypertension, cerebral atherosclerosis, etc. Treatment of DEP should first of all be aimed at the underlying disease. Only optimal control of all existing risk factors for cerebrovascular accidents makes it possible to stop or slow down the progression of cerebrovascular insufficiency. Treatment of the underlying vascular disease thus constitutes etiotropic therapy for DEP. It usually repeats measures for secondary prevention of stroke and includes antihypertensive, antiplatelet, or anticoagulant, and lipid-lowering therapy, and vascular surgery methods.

Pathogenetic therapy for DEP should be aimed at optimizing cerebral blood flow and creating neurometabolic protection of the brain from ischemia and hypoxia.

In everyday practice, vasoactive drugs that affect cerebral microcirculation are most often used. Such drugs include:

• phosphodiesterase inhibitors: pentoxifylline (Vazonit®), vinpocetine, aminophylline, standard ginkgo biloba leaf extract, etc. The phosphodiesterase enzyme is involved in the metabolism of cyclic adenosine monophosphate. An increase in its content in the smooth muscle cells of the vascular wall as a result of a decrease in phosphodiesterase activity leads to their relaxation and an increase in the lumen of the vessels;
• calcium channel blockers - cinnarizine, nimodipine, diltiazem also have a vasodilating effect, which is based on a decrease in the content of intracellular calcium in the smooth muscle cells of the vascular wall;
• α2-adrenergic receptor blockers: nicergoline, piribedil, α-dihydroergocryptine. These drugs eliminate the vasoconstrictor effect of the mediators of the sympathetic nervous system - adrenaline and norepinephrine, and also (due to their effect on cerebral presynaptic receptors) increase the activity of noradrenergic mediation in the brain.

An effective vasoactive drug that has proven itself in many years of clinical practice is pentoxifylline (Vazonit®, Austria). This drug is a derivative of methylxanthine, which has the ability to effectively inhibit type 4 phosphodiesterases in smooth muscle cells of the vascular wall and blood cells. The use of Vasonite leads to the expansion of small-caliber cerebral vessels. At the same time, according to experimental data, the drug has the greatest effect on the affected vessels in the ischemic parts of the brain. Therefore, the appointment of Vazonit does not cause the effect of “robbing”. In addition, inhibition of phosphodiesterase in blood cells reduces the aggregation activity of platelets and erythrocytes, increases the deformability of platelets and erythrocytes and reduces blood viscosity [27–30].

The dosage form of Vazonit is long-acting tablets, which allows you to take them 2 times a day - morning and evening. In this case, there are no night breaks in treatment, i.e., a full day is “overlapping” with a 2-time dose.

Pentoxifylline can be prescribed both orally and intravenously with a fairly wide range of doses. However, it is recommended to prescribe pentoxifylline in tablets of 600 mg (extended form) 2 times a day with food.

The effect of pentoxifylline can occur between the 2nd and 4th weeks, but treatment should continue for at least 8 weeks. [31].

The high effectiveness of pentoxifylline has been demonstrated both in numerous clinical studies and in many years of daily clinical practice. Thus, in the study of A.N. Boyko et al. Pentoxifylline was prescribed to 55 patients with consequences of non-severe stroke. With this therapy, a significant improvement in memory, attention and other cognitive functions was noted [27].

In the 1980s–1990s. More than 20 randomized, double-blind, placebo-controlled studies have been conducted in European countries. Their results convincingly showed that the use of pentoxifylline in patients with vascular dementia and less severe cognitive impairment is accompanied by a significant improvement in cognitive function, as well as regression of other neurological disorders. At the same time, therapy with pentoxifylline contributed to a clinically significant reduction in the severity of cognitive and other neurological disorders both in CNMC and in dementia that developed as a result of repeated acute cerebrovascular accidents [28–30].

Over a long period of practical use, pentoxifylline has shown a high safety profile and good tolerability, including in elderly patients. The drug does not have a negative effect on vital functions and extremely rarely causes side effects [28–30].

In domestic practice, vasoactive drugs are usually prescribed in courses of 2–3 months. 1–2 rubles/year. However, recently the feasibility of longer-term vascular therapy has been discussed.

Neurometabolic therapy is also widely used for DEP. The goals of this type of treatment are to create neurometabolic protection of the brain from ischemia and hypoxia, as well as to stimulate reparative processes in the brain. Neurometabolic drugs include piracetam, ethylmethylhydroxypyridine succinate, choline alfoscerate, citicoline, etc.

Metabolic therapy is carried out in courses of 1–2 rubles/year. Pathogenetically justified and appropriate is the combined implementation of vasoactive and metabolic therapy.

In conclusion, it should be emphasized that influencing both the cause and the main symptoms of DEP will undoubtedly contribute to both slowing down the progression of DEP and regressing existing symptoms and, ultimately, improving the quality of life of patients and their relatives.

Diagnosis and treatment of chronic cerebrovascular insufficiency

The article identifies the most common causes of vascular cognitive impairment and their characteristic manifestations. It is noted that vascular cognitive impairment is often combined with emotional disorders. Methods for diagnosis, treatment and prevention of vascular cognitive impairment are discussed. Using choline alfoscerate as an example, the possibility of using drugs with neurometabolic action in chronic cerebrovascular insufficiency is considered.

Rice. 1. The mechanism of formation of symptoms of dyscirculatory encephalopathy

Rice. 2. Montreal Cognitive Function Rating Scale. Test sheet

Table 1. Indicators of cognitive functions in 23 patients with dyscirculatory encephalopathy during treatment with Cereton (M ± m, points)

Rice. 3. Dynamics of the main clinical indicators during treatment according to the Brief Mental Status Scale (MSMS) and the Visual Analog Scale (VAS)

Rice. 4. Evaluation of treatment results by the patient and the doctor

Rice. 5. Indicators of the level of anxiety and depression according to the hospital anxiety and depression scale in patients at the start and end of treatment with Cereton

Table 2. Dynamics of the studied indicators during the treatment (M ± m, points)

Rice. 6. Indicators of quality of life in patients at the start and end of treatment with Cereton according to the SF-36 questionnaire

Introduction

Currently, the appeal of patients with vascular diseases of the brain, including stroke and chronic insufficiency of blood supply to the brain, is an extremely pressing problem not only for neurologists, but also cardiologists, therapists and doctors of other specialties.

Chronic cerebral vascular insufficiency is one of the main causes of the development of cognitive impairment and dementia, as well as disability in old age. It is generally accepted that the cardinal clinical sign of chronic vascular brain damage is vascular cognitive impairment. Vascular cognitive impairments are impairments of cognitive functions of varying severity, which are formed as a result of stroke and/or long-term chronic cerebral circulatory failure. The structure of vascular cognitive impairment includes mild and moderate cognitive impairment, vascular dementia, which is the second most common cause of acquired dementia (after Alzheimer's disease).

In domestic neurological practice, the syndrome of chronic vascular progressive brain damage is designated by various terms: discirculatory encephalopathy, chronic cerebral ischemia, etc. Typically, discirculatory encephalopathy of the first stage corresponds to mild cognitive impairment, discirculatory encephalopathy of the second stage corresponds to moderate cognitive impairment, discirculatory encephalopathy of the third stage corresponds to vascular dementia. .

Etiology and pathogenesis

The most common causes of vascular cognitive impairment are cerebral atherosclerosis, arterial hypertension, diseases of the cardiovascular system with a high risk of embolism in the brain (for example, atrial fibrillation, heart valve pathology, coronary heart disease), diabetes mellitus.

Due to some anatomical and physiological characteristics of the cerebral circulation, there are parts of the brain that are more and less vulnerable to ischemic damage. Physiologically, the deepest structures are in the most unfavorable position: the subcortical gray nodes and the periventricular white matter of the cerebral hemispheres. According to statistics, it is here that focal and diffuse changes in the brain substance associated with ischemic damage are formed earlier and most often [1–4].

The deep sections of the cerebral white matter are located on the border of the carotid and vertebral-basilar basins (watershed zone), and therefore suffer when the main arteries of the head are damaged, for example as a result of atherosclerosis. Microangiopathy of penetrating arteries due to long-term uncontrolled arterial hypertension, diabetes mellitus or other diseases affecting small-caliber vessels also leads to damage to the above departments. Thus, the consequence of damage to both large and small vessels can be damage to the subcortical structures and deep parts of the white matter of the brain. As a result, the phenomenon of disconnection is formed - a disruption of communication between the cortical and subcortical parts of the brain. The phenomenon of disconnection determines the main clinical manifestations of dyscirculatory encephalopathy, which are primarily based on dysfunction of the frontal lobes of the brain. This is due to the special psychophysiological role of the frontal lobes, which plan and control cognitive activity and voluntary behavior. Disruption of communication with other cerebral structures significantly complicates the implementation of this function (Fig. 1) [2, 5–7].

Clinical picture

A sign of vascular cognitive impairment is considered to be a decrease in cognitive function that goes beyond the age norm due to cerebrovascular disease. In this case, it is necessary to ensure that there is a cause-and-effect relationship between cognitive disorders and vascular damage to the brain. Despite the highly variable clinical picture, vascular cognitive impairment in the vast majority of cases is represented by a violation of the so-called executive functions of the brain (planning, control) in combination with visuospatial and soft mnestic disorders. Typically, vascular cognitive impairment is combined with changes in the emotional and behavioral sphere in the form of a decrease in mood, affect lability, and depression [8–10].

At the stage of mild cognitive impairment, the pace of cognitive activity decreases, concentration deteriorates, episodic forgetfulness and increased fatigue during mental stress occur. To diagnose mild cognitive impairment, a detailed neuropsychological examination is necessary. Simple screening techniques, such as the Mini-Mental State Examination, the Clock Drawing Test, and the Frontal Test Battery, as a rule, do not detect disorders [11, 12].

Moderate cognitive impairment is indicated by its more persistent and definite nature. At the same time, impairments in memory and other cognitive functions clearly go beyond the age norm, but do not deprive the patient of independence in everyday life, that is, they do not reach the severity of dementia [8, 9, 10]. The most typical disorders are the planning and control of cognitive activity and behavior, as well as the ability to generalize and draw conclusions. These disorders reflect dysfunction of the anterior parts of the brain. In typical cases, memory suffers mildly in the form of difficulties in reproducing information while the ability to memorize is intact. Memory of life events remains largely intact. In the absence of strokes, speech disorders (aphasia) are not common [1, 6, 8–10, 13–15].

Vascular dementia, an extreme manifestation of vascular cognitive failure, usually develops many years after the onset of the pathological process. The transformation of mild cognitive impairment into dementia is indicated by the patient's dependence on outside help due to cognitive impairment. The presence of such a dependence is evidenced, in particular, by the impossibility or significant difficulties of independent interaction between the patient and the doctor, when the patient cannot accurately tell the history of the disease, does not follow the doctor’s recommendations due to forgetfulness or other cognitive disorders [10, 16].

As mentioned above, before the formation of vascular dementia, and often at the stage of mild dementia, the presence of cognitive impairment may not be obvious during routine collection of complaints and anamnesis. To objectify cognitive status when working with elderly patients with arterial hypertension, cerebral atherosclerosis and other vascular diseases, neuropsychological techniques should be used. The simplest screening technique is the Mini-Cog test, which is a three-word memorization test combined with a clock drawing test [17]. It should be noted that this technique is not very informative for mild and moderate cognitive disorders. For a more accurate assessment of the cognitive status in these cases, the Montreal Cognitive Assessment is currently being actively positioned, which contains tests for executive functions of the brain (number-letter connection test, choice reaction), memory, orientation, drawing geometric figures, etc. (Fig. 2).

Emotional disturbances

Quite often, vascular cognitive impairment is combined with emotional disorders in the form of vascular depression, emotional lability, decreased motivation and apathy. Depression in vascular cognitive impairment is organic in nature and is associated with functional isolation of the frontal lobes of the brain due to the phenomenon of disconnection (see above). Patients themselves rarely complain of depression or decreased mood. The most characteristic symptom is a painful fixation on unpleasant somatic sensations that cannot be fully explained by existing diseases. Typical complaints are headaches, pain in the back, joints, internal organs, dizziness, noise and ringing in the head. Vascular depression is characterized by a protracted course and responds poorly to antidepressant therapy [6, 11, 16].

Another characteristic type of vascular emotional disorders is emotional lability, which is a rapid change in mood and a tendency to explosive reactions. There are episodes of uncontrollable crying that occur for minor reasons, irritability and aggressiveness towards others [6, 11, 16].

Patients with established vascular dementia syndrome often experience an emotional disorder such as apathy. It is manifested by a decrease in motivation and independent motivation for any activity. Patients lose interest in their previous hobbies, do nothing most of the time or are engaged in unproductive activities [1, 11].

Diagnostics

To diagnose vascular cognitive impairment, it is necessary to carefully study the medical history, assess the neurological status, and apply neuropsychological and instrumental research methods (primarily neuroimaging). It is important to note that a prerequisite for correct diagnosis is obtaining convincing evidence of a cause-and-effect relationship between neurological and cognitive symptoms and cerebrovascular pathology.

Neuroimaging methods play an important role in examining patients and establishing the vascular nature of symptoms: computed x-ray or, preferably, magnetic resonance imaging of the brain. This research method allows you to visualize the consequences of acute brain disorders and diffuse changes in the white matter (leukoaraiosis). The presence of these changes confirms the vascular nature of brain damage [10, 13, 15].

Treatment

Treatment of patients with chronic cerebrovascular insufficiency should be aimed at preventing stroke and progression of chronic cerebrovascular pathology, and improving cognitive functions. The choice of a specific drug is determined by the severity and nature of the symptoms, the presence of concomitant diseases in the patient, and drug tolerability [18, 19].

To prevent acute cerebrovascular accidents, timely correction of known risk factors for strokes (low physical activity, obesity, smoking, alcohol abuse), treatment of arterial hypertension, coronary heart disease, and diabetes are necessary. Normalization of blood pressure is recognized as one of the most effective areas of stroke prevention. However, caution should be exercised in adjusting blood pressure in patients with severe stenosis or occlusion of at least one extracranial or intracranial cerebral artery. If a hemodynamically significant stenosis of the cerebral arteries is detected, it is advisable to consult with a vascular surgeon to decide on surgical treatment.

For secondary prevention of stroke in patients who have suffered a transient ischemic attack or acute cerebrovascular accident of non-cardioembolic origin, antiplatelet therapy is recommended. These drugs include acetylsalicylic acid at a dose of 75–300 mg/day or clopidogrel at a dose of 75 mg/day.

In cases of acute cardioembolic cerebrovascular accidents, atrial fibrillation, and valvular heart disease, oral anticoagulants are used. Warfarin has long been the drug of choice. This drug is prescribed in a dose of 2.5 to 10 mg/day under the control of the international normalized ratio (it should be in the range from 2 to 3). Currently, new oral anticoagulants that do not require international normalized ratio control (dabigatran, rivaroxaban, apixaban) are also actively used.

To correct dyslipidemia, drugs from the group of statins are prescribed.

For depression in patients with chronic cerebral vascular insufficiency, psychotherapy and the use of antidepressants are indicated. However, you should refrain from prescribing drugs with anticholinergic properties (for example, tricyclic antidepressants), which may have a negative effect on cognitive status. To improve cognitive functions at the stage of vascular dementia, acetylcholinesterase inhibitors (donepizil, galantamine, rivastigmine) and/or the glutamine receptor blocker memantine can be used. Systematic exercises to train memory and attention (cognitive training) also play an important role in maintaining cognitive functions [14, 19, 20].

Neurometabolic drugs are actively used to treat chronic cerebrovascular insufficiency. The drug of choice may be choline alfoscerate (Cereton), which has a high level of evidence, safety and good tolerability. A feature of Cereton therapy is the rapid onset of the effect, both subjectively (during the first week) and objectively (after two to four weeks). At the same time, restoration of cholinergic neurotransmission during the use of Cereton leads not only to a reduction in neurological and cognitive disorders, but also to a decrease in symptoms of anxiety and depression, as well as an increase in the quality of life of patients.

Cereton is a compound containing 40.5% protected choline, which is electrically neutral. The mechanism of action of the drug is based on the fact that when it enters the body under the action of enzymes, it is split into choline and glycerophosphate. The resulting choline is electrically neutral, due to which it penetrates the blood-brain barrier and enters the brain, where it serves as the basis for the formation of acetylcholine. Deficiency of the latter in the brain has pathogenetic significance in neurodegenerative and vascular diseases, accompanied by a decrease in memory and other cognitive functions. Choline stimulates the synthesis of acetylcholine in the brain, improves the transmission of nerve impulses in cholinergic neurons. Glycerophosphate, being a precursor of neuronal membrane phospholipids, stimulates the formation of phosphatidylcholine, which restores the phospholipid composition of neuronal membranes and improves their plasticity [20, 21].

The clinical efficacy and tolerability of choline alfoscerate in dyscirculatory encephalopathy have been studied in several clinical studies.

L. Parnetti et al. [22] analyzed the results of 13 clinical studies of choline alfoscerate, including double-blind studies, involving a total of 1570 patients with Alzheimer's disease or vascular dementia. During the therapy, a significant improvement in cognitive functions (memory, attention) and emotional state (decreased irritability, emotional lability), and a decrease in the severity of general weakness and dizziness were noted. The study drug was safe and well tolerated in elderly patients.

The effectiveness of choline alfoscerate in post-stroke cognitive impairment was reported in a study by SG Barbagallo et al. [23]. As a result of long-term follow-up, improvements in cognitive function and other indicators of neurological status were shown. A significant improvement in cognitive function was found in 71% of the 2044 patients participating in the study. The drug was also well tolerated and had a low incidence of side effects.

The effectiveness of Cereton in dyscirculatory encephalopathy was studied in the work of L.P. Ponomareva et al. [24]. The study included 23 patients with dyscirculatory encephalopathy of the first and second stages (average age 60 ± 1.2 years) with moderate cognitive impairment. Patients with discirculatory encephalopathy received antihypertensive therapy (n = 20), antiplatelet agents (n = 23), statins (n ​​= 20). Cereton therapy was carried out according to the following regimen: 1000 mg intravenously daily for ten days. Other neurometabolic or vasoactive agents were excluded. As a result, all 23 patients with dyscirculatory encephalopathy showed positive dynamics in their neurological status and cognitive functions (Table 1). Almost all patients noted good tolerability of the drug.

T.N. Batysheva et al. conducted a study to evaluate the effectiveness of Cereton in patients with moderate cognitive disorders of vascular origin [25]. The authors observed 46 patients (19 men and 27 women) aged 39 to 59 years (average 43.8 ± 7.2 years) with moderate cognitive disorders of vascular origin on an outpatient basis. Cereton was administered at a dose of 1000 mg/day intramuscularly for 15 days. The drug was well tolerated, subjective improvement in the patients' condition, and a statistically significant improvement in cognitive function indicators assessed using the Brief Mental Status Assessment Scale (an average increase of 1.5 points) (Table 2, Fig. 3 and 4).

I.D. Stulin et al. presented the results of an open, non-comparative study of the effectiveness of Cereton in 25 patients with dyscirculatory encephalopathy of the first and second stages [26]. All patients were administered Cereton at a dose of 1000 mg/day intravenously for five days, then intramuscularly for another ten days. All patients were assessed for neurological status, severity of cognitive and emotional disorders. Computed or magnetic resonance imaging of the brain, duplex scanning of the brachiocephalic arteries, transcranial Doppler sonography and electroencephalography were performed. As a result of treatment, an improvement in well-being was noted, night sleep was normalized, the level of anxiety decreased, and the severity of focal neurological symptoms decreased. By the third week of treatment, there was a statistically significant improvement in memory scores, a trend towards improvement in attention scores and test performance speed. When electroencephalography was repeated in 14 patients, positive dynamics of bioelectrical activity of the brain was observed in the form of a decrease in the representation of slow waves and an increase in the presence of the alpha rhythm.

There is evidence of the effectiveness of choline alfoscerate in Alzheimer's disease combined with cerebrovascular disease. The ASCOMALVA double-blind, multicenter trial is currently underway. The preliminary results of the study are based on a 12-month follow-up analysis of 91 patients aged 56 to 91 years, mean age 75 ± 10 years. Patients were randomized to treatment with a combination of donepizil and choline alfoscerate or donepizil monotherapy. The dynamics of symptoms were analyzed at the third, sixth, ninth and 12th months of treatment. Cognitive functions, daily activities of the patient and the severity of behavioral disorders were assessed. As a result, it was found that the use of a combination of donepezil and choline alfoscerate has advantages compared to donepizil monotherapy [27].

N.V. Pizova studied the effect of Cereton not only on cognitive functions, but also on indicators of quality of life (a specific questionnaire for assessing the patient’s quality of life - Short Form-36), as well as on the level of anxiety and depression using the Hospital Anxiety and Depression Scale Scale) [28]. To 25 patients with moderate cognitive impairment of vascular etiology, Cereton was prescribed at a dose of 1000 mg in 200 ml of saline for 15 days, and then treatment was continued on an outpatient basis at a dose of 400 mg (one capsule) three times a day for three months. During therapy, a decrease in the severity of cognitive impairment and other neurological symptoms and moderate cognitive impairment was noted: the score on the Mini-Mental State Examination increased from 25.6 to 28.7. Statistically significant decreases in the severity of anxiety and depression and a significant improvement in the quality of life of patients were also noted. Subjectively, the therapeutic effect was determined already in the first week (from the fifth to sixth day), and from the 15th day it was recorded using objective research methods (Fig. 5 and 6).

It is recommended to begin treatment with Cereton with injections of 1000 mg/day for 15 days, then switch to oral administration of one capsule (400 mg) three times a day for six months. This course allows you to achieve reliable and stable clinical results. However, it must be taken into account that discirculatory encephalopathy is a chronic disease with a progressive course, especially in some cases (a combination of discirculatory encephalopathy with arterial hypertension, coronary heart disease, diabetes mellitus). For this reason, to improve the prognosis of vascular cognitive impairment, it can be recommended to repeat injection courses three to four times a year and constantly take Cereton capsules in the interval between injection courses.

Conclusion

Thus, timely diagnosis of the disease and elimination of existing vascular risk factors can significantly improve the prognosis of vascular cognitive impairment, preserving the ability of patients to work for a long time. Treatment of vascular cognitive impairments themselves must begin immediately from the moment they are identified. This will significantly slow down the dynamics of their development and improve the patient’s quality of life.