[Pharmacological approaches to the therapy of Alzheimer's disease]

The role of apolipoprotein E (ApoE) genotype in the forming of response to various kinds of pathogenetic therapy of Alzheimer's disease (AD) was studied in two samples of patients receiving cholinergic or neurotrophic therapy during four months. The samples were formed by pair control method according to the following parameters: clinical type of AD (presenile or senile) and the severity of dementia (mild or moderate). The average scores according to cognitive scales (MMSE and ADAS-cog) and to the scale which evaluates the everyday activity of patients (IADL) were practically identical. Patients in group I were treated with exelon (rivastigmine) in maximal individually tolerable doses (76.7% of the patients were receiving > or = 6 mg/ day). Patients in group II received two courses of cerebrolysin (20 i.v. injections of 30.0 ml of the drug in 100 ml of normal saline) with an 8-week break. Both treatments had a significant therapeutic effect, but the proportion of responders to different kinds of therapy depended on ApoE genotype. Among ApoEepsilon4(+) patients the proportion of responders was practically equal in both treatment groups (30.8% and 31.2%), while among ApoEepsilon4(-) patients the proportion of responders to cerebrolysin was three times as big as the proportion of responders to exelon (47.0 and 14.3%, respectively). In the cerebrolysin group the proportion of responders was 1.5 times bigger among ApoEepsilon4(-)patients, while in the exelon group, on the contrary, the proportion of responders was twice bigger among ApoEepsilon4(+) patients (31.2% and 14.3%, respectively). Long-term effects of cerebrolysin (two months after the end of the treatment) in ApoEepsilon4(-) patients were also higher than those in ApoEepsilon4(+) patients, while in exelon patients long-term effects did not depend on ApoEepsilon4. The study demonstrates the significance of the detection of ApoEepsilon4 genotype for the choice of a therapeutic approach in patients with mild or moderate dementia caused by AD.