Cognitive disorders

Post-stroke cognitive impairment

Post-stroke cognitive impairment can be presented in a wide range, from mild dysfunction (decreased concentration of attention, decreased speed of solving cognitive tasks, mild memory impairment) to the degree of dementia (inability to perform the usual daily functional duties). However, if such vivid forms of CD as dementia in patients who have had a stroke are often recognized and corrected at the early stages of the disease, then milder and moderate forms of PICI often go unnoticed.

The literature mainly discusses data on vascular dementia that develops as a result of impaired cerebral blood flow, which accounts for 15% of all types of dementia and ranks second in frequency after Alzheimer’s disease. Recently, there is more and more talk about the combination of these two types of dementia – vascular and degenerative, suggesting that pre-existing Alzheimer’s disease clinically manifests only against the background of an acute vascular event. Dementia, as a rule, does not form immediately, but several months after a stroke. In the first 3-6 months , its frequency varies, according to various sources, from 5 to 32%, and after 12 months – from 8 to 26%. At the same time, a high risk of developing dementia persists in the long term. Data from observational studies indicate that the proportion of patients with dementia among the total number of stroke survivors is 7% within 1 year, 10% after 3 years, and 48% after 25 years. Currently, PICI refers to any cognitive disorders that have a temporal relationship with stroke, i.e. are detected in the first 3 months after it (early PUCI) or at a later date, but usually not later than a year (late PUCI). A three-month interval is introduced into the NINDS-AIREN criteria for vascular dementia ( National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherche et l’Enseignement en Neurosciences ) as one of the evidence for a causal relationship between cerebrovascular disease and dementia. The later PICI is detected, the more difficult it is to find a direct link between their occurrence and stroke. The results of large studies indicate that the risk of developing PICI does not depend on the nature of the stroke (ischemic, hemorrhagic), pathogenetic variant ( atherothrombotic , cardioembolic , lacunar), the severity of the neurological deficit and the severity of the stroke. According to the severity and prevalence of CD, three variants of PICI are distinguished: focal, arising from focal damage to the strategic zone of the brain (SM) and manifested by damage to one cognitive function (aphasia, amnesia, apraxia, agnosia); multiple, not reaching the degree of dementia (post-stroke mild cognitive impairment); multiple, accompanied by a violation of social adaptation, regardless of the motor or other focal neurological deficit (post-stroke dementia).

Focal PICI are caused by focal damage to brain structures that are directly related to the regulation of cognitive activity. Such cases are characterized by acute or subacute development of CD with subsequent stabilization and full or partial recovery. Thus, memory impairment in the absence of dementia is noted in 23–55% of patients in the first 3 months after a stroke, and by the end of the 1st year, the number of such patients decreases to 11–31%. The list of strategic zones is varied, but most often the CD is observed It occurs when the zones included in the pool of the anterior and posterior cerebral arteries (prefrontal cortex , medial parts of the temporal lobes, thalamus), basal ganglia (caudate nucleus, to a lesser extent – pale ball), as well as the junction of the occipital, temporal and parietal cortex ( especially the angular gyrus). Gradual or step-like increase in post-stroke dementia or moderate cognitive impairment is less associated with acute processes occurring in the brain during stroke. Most often, it is caused by microvascular pathology ( multiple , including “silent” lacunar infarcts), cerebral atrophy (especially of the medial temporal lobes, in particular the hippocampus), and diffuse damage to the white matter ( leukoaraiosis ) due to chronic cerebral hypoperfusion or a neurodegenerative process. Concomitant somatic diseases, such as diabetes mellitus, atherosclerosis, heart failure, cardiac arrhythmias, dysmetabolic manifestations, exacerbate PICI. Post-stroke cognitive impairment undoubtedly worsens the prognosis and reduces the possibility of recovery in patients who have undergone acute cerebrovascular accident, since the adequacy of rehabilitation treatment is determined by the active participation of patients in this process. Patients with post-stroke dementia have a higher mortality rate and a high risk of recurrent stroke, which is explained by a more extensive GM pathology, severe somatic burden, and low adherence of these patients to treatment and household activities. All these facts dictate the need for careful identification of CD in patients with stroke, even if the patient gives the impression of being “safe”. The use of screening methods for assessing cognitive functions with the further involvement of a psychologist and a psychiatrist is a prerequisite for identifying and correcting changes in the neuropsychic sphere. Thus, PICI is determined by many factors, such as local cerebral vascular damage, diffuse damage to the brain due to background and concomitant diseases, involutional and degenerative processes.

Recovery of cognitive functions in the post-stroke period

Considering the multifactorial nature of PICI, an integrated approach is required to restore cognitive functions. The basis of standard therapy in the post-stroke period is secondary prevention of stroke, aimed at correcting risk factors for stroke and preventing a recurrent episode of stroke. The maximum correction of vascular risk factors affects not only the development of repeated acute cerebrovascular accidents, but also the severity of PICI. An obligatory component of the rehabilitation process is cognitive training.

An individual program for training cognitive functions is based on the results of neuropsychological testing. The program of cognitive training includes the restoration of praxis. Patients are taught to relearn daily practical skills. Purposeful physical activity significantly improves cognitive functions. Drugs used to prevent and restore cognitive functions in stroke patients have different mechanisms of action: influence on typical pathological processes, such as the glutamate-calcium cascade, oxidative stress; neuronal metabolism, reparative -regenerative processes and sanogenesis . With a combination of vascular and degenerative diseases, neurotransmitter processes (acetylcholine, dopamine, glutamate, etc.) are corrected. According to D.F. Mureshan , the only class of substances that can simultaneously provide neuroprotection (multifaceted effects on pathological reactions) and neuroplasticity (stimulation of neurorepair ), are neurotrophic factors and molecules similar to neurotrophic factors.

These substances are contained in the drug Cerebrolysin, which has been successfully used in neurological practice for a long time. Cerebrolysin consists of a compositionally balanced mixture of active fragments of low molecular weight neuropeptides, free amino acids, micro and macro elements. The drug is a product of proteolytic cleavage of the protein components of the brain of pigs, free from lipids. The molecular weight of Cerebrolysin peptides does not exceed 10,000 Da, which makes it possible for the peptides to penetrate the blood-brain barrier and actively involve them in the metabolism of neurons.

Neuroprotection itself includes a complex of pharmacological effects aimed at combating lipid peroxidation, excitotoxicity and an increase in intracellular calcium concentration, microglia activation and immune imbalance, and accumulation of β-amyloid. In recent studies, it has been found that neurotrophic factors exhibit a neuroprotective and neuroregenerative effect (enhance neuroplasticity and stimulate neurogenesis) of the nervous tissue. Since Cerebrolysin contains peptides that are fragments of neurotrophic factors, this drug also exhibits all of the above effects. Maintaining neuroplasticity involves maintaining existing and recreating new interneuronal connections . Several studies have shown that during acute brain injury, such as ischemia, Cerebrolysin inhibits calpain , which prevents the breakdown of MAP2 ( microtubule associated protein 2, a neuronal cytoskeletal protein, is considered as an indicator of the primary stage of neuronal damage), and increases the expression of the gene responsible for the synthesis of MAP2. This leads to the maintenance of the integrity of the cytoskeleton and the normalization of dendritic branching, contributing to the preservation of plasticity and survival of neurons.

Neurogenesis refers to the ability to form new nerve cells. The results of studies indicate that Cerebrolysin enhances neurogenesis in the adult brain both in healthy rats and after modeling Alzheimer’s disease in transgenic mice, mainly the increase in the formation of new neurons was observed in the dentate gyrus of the hippocampus. In another study on a model of cerebral ischemia, it was demonstrated that the drug also increased the number of new neurons in the subventricular region of the lateral ventricles of the rat brain.

The presence of Cerebrolysin’s anti-apoptotic effect not only promotes the restoration of impaired functions, but also protects the cerebral cortex from the development of neurodegenerative changes triggered by the ischemic cascade. To prevent KD, prevention should be started as early as possible, which has been proven in clinical studies on the use of Cerebrolysin not only in the acute and early recovery, but also in the most acute period of stroke. When assessing the degree of recovery of cognitive functions using the MMSE scale ( Mini Mental State Examination – a short scale assessment of mental status) showed significantly better recovery in patients with right-sided stroke during therapy with Cerebrolysin compared with placebo. In addition, the drug has proven itself in the treatment of vascular dementia, with combined vascular degenerative dementia of the Alzheimer’s type, demonstrating a significant improvement in cognitive and functional parameters. These positive effects are reflected in a recent Cochrane review on the use of Cerebrolysin for the treatment of vascular dementia (2013): the advantage of the drug in terms of the effect on cognitive functions on the MMSE and ADAS- cog + scales ( Alzheimer’s disease Assessment Scale – cognitive subscale – a scale for assessing cognitive functions in Alzheimer’s disease) and improving the general clinical condition of patients according to the CGI scales ( Clinical Global impression Scale – a scale of overall clinical impression) and CIBIC + ( Clinician InterviewBased impression of Change – a scale for assessing changes by a clinician based on a survey ).

A meta-analysis on the use of Cerebrolysin in the treatment of mild to moderate Alzheimer’s disease (2007) also found a positive effect of Cerebrolysin on MMSE cognitive function and showed that the drug improves the overall effect of treatment on the CGI scale. Thus, in the early recovery period of a stroke, when carrying out rehabilitation measures, it is necessary to pay attention to the prevention and correction of PICI. Cerebrolysin, which has a neurotrophic and regenerative effect, can be recommended as an effective drug.