Vascular dementia: treatment

From the point of view of public health in vascular dementia, measures for primary prevention of vascular dementia are most effective.

Educational programs that explain the importance of controlling risk factors can reduce the incidence of stroke and the frequency of its complications, including vascular dementia. When vascular dementia has already developed, exposure to vascular risk factors and concomitant somatic diseases can reduce the rate of progression of dementia. In some cases, antiplatelet agents (aspirin, ticlopidine, clopidogrel) or indirect anticoagulants (warfarin) may have some significance.

Exposure to risk factors. Reducing risk factors for stroke can reduce the likelihood of recurrence of cerebral infarction. The use of antihypertensive drugs to reduce arterial hypertension should be carefully monitored, since an excessive drop in blood pressure can lead to relative hypoperfusion, which may be the cause of worsening of cerebral ischemia, the appearance of general weakness, confusion and deterioration of cognitive functions. Cerebral embolism is another treatable factor in the development of stroke. In connection with this, a thorough examination is necessary to detect episodic cardiac arrhythmias with Holter monitoring, and also to establish the character of cerebral embolism with CT and MP angiography, Doppler and echocardiography. In the absence of treatment, atrial fibrillation can lead to a reduction in cardiac output, cerebral hypoperfusion, and the development of ischemia and even cerebral infarction.

At present, the ability of aspirin (at a dose of 325 mg / day) and warfarin (at a dose maintaining an international normalized ratio of 2-4.5) is proven to reduce the risk of a second stroke. To reduce the risk of stroke (and, consequently, vascular dementia), patients with non-rheumatic mertzalnoy arrhythmia in the absence of contraindications should be prescribed warfarin or aspirin (Stroke Prevention in Atrial Fibrillation Investigators, 1991). Anticoagulant therapy reduces the risk of stroke after myocardial infarction. The most serious potential complication of anticoagulant therapy is intracranial hemorrhage, the probability of which can be reduced if the international normalized ratio is maintained at a level of no more than 4.

In men who develop myocardial infarction or ischemic stroke, the level of the system marker of inflammation, the C-reactive protein, has been elevated. The decrease in the level of C-reactive protein in the background of aspirin treatment was accompanied by a reduction in the risk of stroke and myocardial infarction, which indicates the potential effectiveness of anti-inflammatory drugs in preventing these diseases. Carotid endarterectomy is recommended in patients with hemodynamically significant stenosis of carotid arteries (North American Symptomatic Carotis Endarterectomy Trial Collaborators, 1991) and ulcerated carotid plaques. Poorly controlled diabetes mellitus and elevated lipid levels in the blood can reduce cerebral perfusion, causing microangiopathy, which can lead to the development of lacunar infarctions and ultimately to vascular dementia. In this regard, lower triglyceride levels and control of blood sugar can increase cerebral blood flow and reduce the risk of a subsequent cerebral infarction.

Cessation of smoking improves cerebral blood flow and the state of cognitive functions. All smokers should be advised not to smoke, regardless of whether they develop vascular dementia or not. In some cases, gradual detoxification with skin patches with nicotine can help.

Data on the ability of estrogen replacement therapy to reduce the risk of developing vascular dementia are contradictory. Replacement estrogen therapy is currently being carried out for osteoporosis, vasomotor menopausal symptoms, atrophic vaginitis, and hypoestrogenism. The effectiveness of estrogen in cardiovascular diseases, ischemic stroke and vascular dementia can be explained by their ability to reduce platelet adhesion, to lower lipid levels in the blood, to relax the thrombolytic and vasoconstrictor effects of thromboxane A2. However, there is evidence of a negative effect of estrogens.

Aspirin. Aspirin in small doses can reduce the formation of platelet aggregates and, therefore, inhibit thrombus formation. Aspirin also blocks the vasocontractor effect of thromboxane A2. Aspirin reduces the likelihood of recurrent stroke and cardiovascular complications. In one study, aspirin at a dose of 325 mg / day, combined with exposure to stroke risk factors, improved or stabilized cerebral perfusion and cognitive function in patients with mild to moderate multi-infarct dementia. Although it is necessary to test these data in more extensive studies, patients with vascular dementia are recommended to prescribe small doses of aspirin (50-325 mg / day) in the absence of contraindications (for example, indications in the anamnesis of gastric or duodenal ulcer or gastric bleeding).

Ticlopidine. Ticlopidine inhibits platelet aggregation by inhibiting adenosine diphosphate-induced platelet binding to fibrinogen. In the Ticlopidine Aspirine Stroke Study (TASS) study, ticlopidine (250 mg twice daily) is more effective than aspirin (650 mg 2 times a day), with the prevention of a stroke, both with a lethal outcome and without it. When using ticlopidine, there are side effects such as diarrhea, rash, bleeding, severe neutropenia. Skin and gastrointestinal side effects of ticlopidine are usually resolved spontaneously. The possibility of neutropenia requires regular monitoring of the level of leukocytes in the blood.

Cloppdogrel reduces platelet aggregation due to direct inhibition of adenosine diphosphate (ADP) - receptor binding, as well as inhibition of ADP-mediated activation of the glycoprotein IIb / IIIa complex. A number of studies have shown the ability of clopidogrel (75 mg once daily) to reduce in patients who had suffered a stroke, myocardial infarction or peripheral arterial disease, stroke, myocardial infarction, and death associated with cardiovascular disease. According to one of the studies, against the background of taking clopidogrel, the risk of a repeat vascular episode decreased by 8.7% more than with taking aspirin. The tolerability of clopidogrel was good. Unlike ticlopidine, it did not cause neutropenia, and the incidence of gastrointestinal bleeding, dyspepsia, was lower than that of aspirin. At the same time, the incidence of diarrhea, rash and itching in patients taking clopidogrel was higher than with aspirin.

Pentoxphylline. In a 9-month, double-blind, placebo-controlled study, pentoxifylline has been shown to cause some improvement in cognitive functions assessed by standardized scores in patients with multi-infarct dementia diagnosed according to the DSM-III criteria, compared with placebo. The dose of pentoxifylline was 400 mg 3 times a day (European Pentoxifylline Multi-Infarct Dementia Study, 1996).

Cholinesterase inhibitors. In double-blind, placebo-controlled studies, it has been shown that in patients with vascular and mixed dementia, galantamine and donepezil are able to improve cognitive function, daily activity and reduce the severity of behavioral disorders.

Memantine. According to controlled studies, memantine in a dose of 20 mg / day, reduced the severity of cognitive impairment in patients with mild and moderate vascular dementia, especially associated with the lesion of small cerebral vessels.

Non -ognitive disorders. Most studies of this problem have been carried out on patients with the effects of strokes. However, the general principles of pharmacological and non-pharmacological effects set forth herein are applicable to other forms of vascular dementia.

Post-stroke depression. Major depression is detected in 10% of patients who have suffered a stroke. According to another study, in 25% of patients hospitalized for a stroke, the condition meets the criteria for major depression. If you take into account depressive symptoms, regardless of whether they meet the criteria for major depression or not, their prevalence in patients who have had a stroke no more than 2 years ago, increases to 40%.

Major depression in patients with stroke more often develops in the lesion of the frontal cortex of the left hemisphere and basal ganglia, with the closer the lesion to the frontal lobe pole, the more pronounced depressive symptoms.

Unrecognized and untreated depression has a negative impact on the patient's activity in the rehabilitation process, the effectiveness of rehabilitation measures and, ultimately, the degree of recovery of lost functions. This situation remains true even after the regress of depression. With lesion of the left hemisphere, depression is more often accompanied by cognitive impairment than with damage to the right hemisphere.

When examining, it is important to exclude other diseases that, in addition to a stroke, can cause affective disorders. It is proved that post-stroke depression can be treated with antidepressants. Thus, nortriptyline was more effective than placebo in a 6-week, double-blind, placebo-controlled study. However, this drug should be used with caution because of the high incidence of side effects, including delirium, syncope, dizziness, increased drowsiness. In a 6-week, double-blind, controlled trial, the efficacy of a selective serotonin reuptake inhibitor citalopram was also shown. And the differences between citalopram and placebo were especially pronounced in patients with late onset of depression (7 weeks after the stroke). Many patients with early onset of depression experienced spontaneous recovery. In addition, in controlled trials with post-stroke depression, fluoxetine proved to be effective.

Post-stroke anxiety. Anxiety in patients with stroke is closely correlated with depression. In one study, 27% of stroke patients diagnosed with generalized anxiety disorder, with 75% of them having concomitant symptoms of depression. This indicates the need to search for and adequately treat depression in patients with post-stroke anxiety. It is also important to consider that anxiety can be a manifestation of a concomitant disease or a side effect of medications taken.

There have been no systematic controlled studies of the efficacy of pharmacological agents for the treatment of anxiety in patients who have undergone a stroke. To treat anxiety in patients without organic brain damage, benzodiazepines are often used. These drugs can be used with caution in patients who have suffered a stroke. It is recommended to prescribe short-acting drugs that do not form active metabolites (for example, lorazepam or oxazepam) - in order to reduce the likelihood of such side effects as drowsiness, ataxia, confusion or disinhibition. Buspirone can also be effective in post-stroke anxiety, but its effect is only visible in a few weeks. At the same time, when buspirone is used, there is no dependence, drowsiness, and the risk of falls is not significantly increased. With generalized anxiety, the effect can also be obtained with tricyclic antidepressants. This requires careful titration of the dose, careful monitoring for the emergence of possible cholinolytic effects. At present, we do not have data from controlled studies that would help to select a drug and select its dose. When using SSRIs there is no risk of tolerance, a low probability of developing abuse. The drugs are especially useful in the treatment of comorbid depression, which often accompanies post-stroke anxiety.

Post-stroke psychosis. Psychosis in a patient with a stroke can be triggered by a drug or a concomitant disease. Hallucinations are noted in less than 1% of patients with stroke. Post-stroke psychosis is more often observed with right hemispheric lesions involving the parietal-temporal cortex, as well as in patients with cerebral atrophy and epileptic seizures.

The patient with delirium should first of all try to establish its cause and choose the right treatment. First, the clinician must exclude somatic disease or the connection of psychosis with the administration of a substance. In accordance with this, the treatment may consist in the correction of the primary disease, the removal of the toxic drug and symptomatic therapy with the help of antipsychotics (if the psychotic symptomatology creates a threat to the life of the patient or interferes with the examination and treatment).

Neuroleptics. Only a small number of controlled studies evaluating the efficacy of antipsychotics in psychoses in patients with stroke. The general principles of choosing an antipsychotic, determining the effective dose and carrying out its titration are the same as in the treatment of psychotic disorders in patients with Alzheimer's disease. Neuroleptics should be prescribed after a thorough search for the cause of psychosis. If psychosis creates a threat to the life of the patient or treatment regimen, the positive effect of neuroleptics outweighs the risk associated with their use. The choice of an antipsychotic is based more on the profile of side effects than on their effectiveness. If the patient shows signs of parkinsonism, then a drug with moderate activity (for example, perphenazine or loxitol) or a new-generation drug (risperidone, olanzapine, seroquel) should be prescribed, which rarely cause extrapyramidal side effects. Caution should be observed in the appointment of neuroleptics with a pronounced cholinolytic effect, especially in patients with prostatic hyperplasia, orthostatic hypotension or a tendency to urinary retention. Holinoliticheskoe effect of these drugs can enhance the cognitive defect in such patients. When excited and disturbed by swallowing, there may be a need for parenteral administration of an antipsychotic. Many traditional neuroleptics are available in the form for intramuscular injection, and some high-potential drugs can be administered intravenously. When intravenous haloperidol should be used because of the risk of developing pirouette ventricular tachycardia. At the same time, many of the new generation neuroleptics are not available in the form for parenteral administration. Assigning neuroleptics to patients who have suffered a stroke, you should consider the risk of developing tardive dyskinesia or a more rare late akathisia. In this regard, from time to time, attempts should be made to lower the dose or to cancel the antipsychotic.

Post-stroke mania. Mania is very rare in patients who have suffered a stroke. In one study, its prevalence in this category of patients was less than 1%. As with other non-cognitive disorders associated with dementia, a thorough examination is necessary to exclude somatic disease or association with the use of a given drug, since these factors can induce or enhance mania. Pharmacotherapy of mania includes the use of valproic acid, carbamazepine, gabapentin and lithium.

Lithium. The effectiveness of lithium in post-stroke mania in controlled studies has not been studied. Several reports indicate a low lithium efficiency in secondary mania. Caution is necessary in the treatment of post-stroke mania with lithium preparations because of the low therapeutic index. Patients with organic brain damage are particularly sensitive to side effects of lithium. Lithium intoxication can cause neurological symptoms such as tremors, ataxia, dysarthria, extrapyramidal and cerebellar symptoms, nystagmus, delirium and even mania. Before appointing lithium, it is necessary to conduct an electrocardiogram, determination of TSH, electrolyte level, a clinical blood test, to investigate the function of the kidneys. It is also necessary to take into account the possibility of drug interaction - the level of lithium in the blood increases some diuretics and non-steroidal anti-inflammatory drugs. During the reception of lithium, it is necessary to regularly monitor the level of the drug in the blood, ECG, concomitant treatment. Although there are no scientifically validated data on the therapeutic concentration of the drug in post-stroke mania, clinical experience shows that the therapeutic concentration can range from 0.5 to 0.7 meq / L.

Carbamazepine. Controlled studies of the effectiveness of carbamazepine in post-stroke mania were not conducted. According to some reports, patients with bipolar disorder arising on the background of organic brain damage react better to carbamazepine than to lithium. Prior to taking carbamazepine, a blood test should be performed to determine the number of platelets, ECG, to investigate liver function, the sodium content in the blood, the level of TSH. You should also measure the blood levels of other drugs metabolized by the enzyme CYP3A4. Carbamazepine is able to induce its own metabolism, therefore it is necessary to determine the content of carbamazepine in the blood at least once every 6 months, and also whenever a dose change or addition of drugs that can interact with carbamazepine. There are no scientifically developed recommendations regarding the therapeutic level of carbamazepine in post-stroke mania. Accordingly, the dose of the drug should be selected empirically, focusing on the clinical effect. Side effects of carbamazepine include hyponatremia, bradycardia, atrioventricular blockade, leukopenia, thrombocytopenia, ataxia, nystagmus, confusion, drowsiness. Based on theoretical considerations, taking carbamazepine can continue if the number of white blood cells in the blood has decreased to no more than 3000 / μl. In persons sensitive to the side effects of carbamazepine, its initial dose should be less than 100 mg, while it is advisable to use the liquid dosage form of the drug. Titration of the dose is slow because patients who have had a stroke are usually elderly people who have decreased hepatic clearance and the ability of plasma proteins to bind the drug, and therefore the concentration of the active substance is higher.

Valproic acid is another anticonvulsant used to treat post-stroke mania. However, there is no evidence of controlled studies that would confirm the effectiveness of the drug in this condition. Before the start of treatment and during it, it is necessary to evaluate the blood condition and liver function. Side effects include drowsiness, ataxia, cognitive impairment, thrombocytopenia, increased levels of hepatic transaminases, tremor, gastrointestinal disorders, hair loss. Possible drug interaction with other drugs that bind to plasma proteins. Alopecia can be corrected with multivitamins containing zinc and selenium. Reception of the drug can continue if the number of white blood cells in the blood does not fall below 3000 / μl, and the level of hepatic enzymes does not rise more than three times from the upper limit of the norm. Valproic acid can inhibit its own metabolism, and when taking a stable dose of the drug, its level in the blood can increase. The therapeutic level of the drug in the serum with post-stroke mania has not been determined to date. Treatment, especially in persons who are sensitive to side effects, can begin with a dose of less than 100 mg, using liquid dosage forms. With a gradual increase in the dose, the likelihood of side effects from the gastrointestinal tract decreases.

Gabapeptin. Gabapentin, which enhances GABA-ergic transmission, is used to enhance the effect of other anticonvulsants. Controlled studies of gabapentin in post-stroke mania were not performed. This is a relatively safe drug, its main side effect is drowsiness. Gabapentin does not enter into drug interactions and does not form active metabolites.

Other drugs. In the treatment of post-stroke mania, benzodiazepines and antipsychotics can also be used. These drugs are discussed in detail in the sections on post-stroke anxiety and post-stroke psychoses.