Experience in the use of NMDA-receptors in the correction of vascular cognitive disorders

The rational cognition process of the world and interaction with it is carried out with the help of cognitive or person cognitive functions, which include the information perception, its processing, analysis, storage, storage and exchange, as well as the purposeful actions program construction and implementation.
Most often, organic processes such as acute and chronic vascular pathology forms, neurodegenerative diseases, tumors, traumatic brain lesions, neuroinfections, demyelinating diseases, and liquorodynamic disorders can lead to cognitive abilities violations.
Cerebrovascular diseases remain one of the most important medical and social problems, causing huge economic damage and being one of the main reasons for emergency hospitalization, invadidization and adult population mortality.
Violations of higher cerebral functions due to cerebrovascular pathology are called vascular cognitive disorders. On average, about half of stroke patients have vascular cognitive impairment, which, according to different sources, ranges from 40 to 70%. In the first 3-6 months after the stroke, the number of vascular cognitive impairments ranges from 5 to 32%, and after 12 months – from 8 to 26%. The risk of developing dementia is highest in the first 6 months after cerebral circulation, which significantly worsens the recovery prognosis in this category of patients.
According to the classification there are:
– mild cognitive disorders;
– mild cognitive impairment;
– severe cognitive impairment (dementia).
Risk factors for the vascular cognitive impairment development are age and sex of patients, family history, arterial hypertension, atherosclerosis and dyslipidemia, microangiopathy, cardiac pathology, diabetes mellitus, hyperhomocysteinemia, depression. Also, cognitive impairment is more likely to occur in people with a low education and smokers level.
In the pathogenesis of vascular cognitive impairments, the leading role is played by damage to the vascular system with the endothelial dysfunction development, neuronal death due to glutamate-excitotoxicity, and the neurotransmitter disorders progression.
Diagnosis of vascular cognitive impairment, according to the EFNS recommendations, is based on the collection of anamnesis, general neurological and fiscal examination, mental status and cognitive impairment (general assessment assessment, memory, executive and routine functions, activity, behavior, psychotic symptoms), identification and related diseases analysis, blood and liquor analysis. The greatest popularity in the cognitive impairments detection was received in such neuro-psychological tests as the brief mental status scale (MMSE), the frontal dysfunction battery (FAB) and the test of drawing the clock. In all cases, the patient should be tested in dynamics, since the dementia diagnosis is authorized 6 months after the onset of cognitive impairment. An important role in examining patients and establishing the vascular nature of symptoms is played by neuroimaging methods: X-ray computed tomography or magnetic resonance imaging of the brain.
The vascular cognitive impairment peculiarity is their potential reversibility under the timely adequate therapy condition. The therapy goals for vascular cognitive impairment include slowing the cognitive disorders progression rate, secondary dementia prevention, as well as reducing the severity of existing disorders in order to improve the patients life quality and their relatives.
The main groups of pharmacological drugs that correct cognitive impairment are: acetylcholinesterase inhibitors, glutamate NMDA receptor antagonists; vasoactive drugs and others.
An important role in the pathogenesis of cerebral ischemia and neurodegeneration is the neurons damage with excess glutamic acid, the so-called glutamate excitotoxicity. AP-7 is a competitive antagonist of glutamate receptors, which is universally used for the dementia therapy of various genesis. This drug quickly and reversibly binds to activated receptors and exerts a voltage-dependent effect that avoids during the mental disorders reception, as in other NMDA antagonists. A number of placebo-controlled randomized trials showed the efficacy and safety of AP-7. A meta-analysis of the studies confirmed its corrective effect in the disturbances of patients’ behavior, increased excitability, aggression, as well as improving the relatives life quality. The positive effect of AP-7 on cognitive functions in vascular dementia with a minimal number of side effects was shown, the best effect was revealed in patients with lesions of small cerebral arteries. Therapy begins with 5 mg per day, increasing the dose by 5 mg per week, to 20 mg per day for long-term use.
At the expressed infringement of liver function and kidneys the reduction of a daily dose to 5-10 mg is recommended.
Thus, the timely and competent vascular cognitive impairment treatment is an important direction in the cerebrovascular disorders treatment.

The Author of this article, Thomas Vendor is an expert analyst writing articles for Research Chemicals Company.



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