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Alzheimer's disease.

During the period under review great attention was paid to mild forms of dementia of the Alzhermer's type, which may play an important role both for the treatment and for the prevention of dementia of the Alzheimer's type.

By means of a follow-up method 3 types of a psychoorganic syndrome in its development were established: stable, progressive, with transitory deterioration. Specificities of the development of a psychopathological syndrome were analysed, including its cognitive and non-cognitive components, as well as a contribution of somatic, psychogenic and some social-environmental factors to the outcomes of psychoorganic syndrome.

A corresponding neuropsychological study demonstrated that modal-nonspecific deterioration of memory noticed in all the patients was first and foremost due to heightened inhibition of traces by interfering activity. At the same time the volume of memorizing practically corresponded to the age norm. Sufficient safety of operational level of activity and a very slight decrease in the ability to control and program one's activities was revealed.

The role of a prognostic value of somatoneurologic, stressogenic and social-environmental factors in the development of psychoorganic syndrome in the elderly patients was established on the basis of a general out-patient setting.

New methods of treatment of Alzheimer-type dementia and dementia of a combined (Alzheimer-vascular) genesis were studied in clinical trials. Clinical trials of new forms of medication for the treatment of mental disorders of a vascular and Alzheimer nature and depressive conditions in the elderly were carried out as well.

A double-blind placebo-controlled study of the efficacy of Cerebrolysin (drip infusions) was conducted in accordance with the method developed in the Department.

During the study of Alzheimer's disease by means of methods of molecular genetics the linkage was found and the locus was mapped on the 14q chromosome responsible for early family forms of Alzheimer's disease. The basic gene (preseneline 1) responsible for the majority of the early family forms of Alzheimer's disease was found and cloned as well as mutations in it. A new gene (preseneline 2) responsible for the early and late family forms of Alzheimer's disease was discovered.

For the first time it was demonstrated that the 4th allele of E apolipoprotein gene (APOE) is a widespread genetic risk factor of Alzheimer's disease and a number of other types of dementia in the Russian population. It was established that in carriers of E4 genotype the risk of the development of the disease is 10 times higher than in individuals with other genotypes. Molecular markers were developed for direct preclinical diagnostics of Alzheimer's disease (mutations in preseneline 1 and preseneline 2 genes and polymorphism in APOE gene).

General regulatory elements of expression of genes taking part in the development of Alzheimer's disease were revealed and modulation of expression of synaptic membrane proteins in case of Alzheimer's disease was detected.

It was established that a heightened production of interleukin-1 is characteristic of the development of Alzheimer's disease especially at its early stages. A heightened synthesis of interleukin-6 in microglial brain elements may result in an uptake of abnormal amyloid protein (b-amyloid) determining the basic alterations in brain tissue in case of the given disease.

It was established that being in concentrations similar to these in the brain of patients with Alzheimer's disease, aluminium ions (Al) bring about hyperphosphorilinary of t-protein (one of the markers of Alzheimer's disease).