[Russian experience in using a combination of fixed doses of donepezil and memantine in the treatment of Alzheimer's disease as an observational non-interventional multicenter program]. / Rossiiskii opyt primeneniya kombinatsii fiksirovannykh doz donepezila i memantina v terapii bolezni Al'tsgeimera v ramkakh nablyudatel'noi neinterventsionnoi mnogotsentrovoi programmy.

OBJECTIVE: To evaluate the efficacy, safety, and compliance to therapy with Mioreol, first used as part of routine clinical practice in patients with moderate-to-severe dementia due to AD. MATERIAL AND METHODS: The study was conducted as a non-interventional observational program. The work was performed on a group of 48 patients with moderate-to-severe AD aged from 60 to 90 years (median age 74 [69; 77]). The therapeutic dose of Mioreol was 10 mg donepezil + 20 mg memantine, the drug was taken orally, once a day at the same time, regardless of meals. The duration of the course of therapy was 24 weeks. The effects of the drug were assessed using the MMSE, ADAS-Cog, NPI, and CGI scales before the start of therapy and by the end of 12 and 24 weeks of treatment. RESULTS: The use of Mioreol in six-month therapy of AD patients with moderate-to-severe dementia improved not only cognitive but also a wide range of non-cognitive mental disorders. There was an improvement in the CGI-C scale in more than 50% of included patients, positive dynamics on the ADAS-cog scale (6.5 points reduction in total score) and reduction of non-cognitive mental disorders on the NPI scale (4 points reduction in total score). CONCLUSION: Fixed-dose combination therapy with Mioreol is an effective and well-tolerated treatment option for patients with moderate-to-severe AD. A combination of fixed-dose therapeutic doses of donepezil and memantine is potentially more appropriate than the simultaneous use of two recommended drugs for the treatment of AD, which will improve treatment adherence in patients with moderate to severe AD.

[Anti-inflammatory effects of neurotrophic therapy (a pilot study)]. / Protivovospalitel'nye éffekty neirotroficheskoi terapii (primenenie tserebrolizina pri miagkom kognitivnom snizhenii).

AIM: To study clinical effects of cerebrolysin and its impact on systemic inflammation markers and immunity in mild cognitive impairment (MCI). MATERIAL AND METHODS: Twenty patients with MCI were treated with cerebrolysin administered intravenously during 4 weeks. Serum levels of immunoglobulins, inflammatory markers, neurotrophic factors were measured in dynamics in patients and controls using ELISA. RESULTS: An effect of cerebrolysin was found in MCI patients including the older group (mean age 78±1.1 years). An improvement was seen 6 and/or 22 weeks after treatment. Four types of response to neurotrophic treatment (fast long-term, fast short-term, delayed long-term), without effect were determined, the longer duration of positive effect of cerebrolysin was shown. There were differences in the indices of humoral immunity, clinical blood test results, cortisol and neurotrophin levels assessed before and after treatment between the patients with- and without positive effect of cerebrolysin. CONCLUSION: The high clinical effect of neurotrophic therapy with cerebrolysin in MCI shows its anti-inflammatory and immunotropic action that suggests the impact of cerebrolysin on the pathogenesis of MCI.

Indications of proton-dominated cosmic-ray composition above 1.6 EeV.

We report studies of ultrahigh-energy cosmic-ray composition via analysis of depth of air shower maximum (X(max)), for air shower events collected by the High-Resolution Fly's Eye (HiRes) observatory. The HiRes data are consistent with a constant elongation rate d/d[log(E)] of 47.9+/-6.0(stat)+/-3.2(syst) g/cm2/decade for energies between 1.6 and 63 EeV, and are consistent with a predominantly protonic composition of cosmic rays when interpreted via the QGSJET01 and QGSJET-II high-energy hadronic interaction models. These measurements constrain models in which the galactic-to-extragalactic transition is the cause of the energy spectrum ankle at 4x10(18) eV.

First observation of the Greisen-Zatsepin-Kuzmin suppression.

The High Resolution Fly's Eye (HiRes) experiment has observed the Greisen-Zatsepin-Kuzmin suppression (called the GZK cutoff) with a statistical significance of five standard deviations. HiRes' measurement of the flux of ultrahigh energy cosmic rays shows a sharp suppression at an energy of 6 x 10(19) eV, consistent with the expected cutoff energy. We observe the ankle of the cosmic-ray energy spectrum as well, at an energy of 4 x 10(18) eV. We describe the experiment, data collection, and analysis and estimate the systematic uncertainties. The results are presented and the calculation of the statistical significance of our observation is described.