Aim: To evaluate the influence of metabolic syndrome (MS) and a history of heart disease on increased mortality rates among patients with Alzheimer's disease (AD) who have been treated with cholinesterase inhibitors or memantine and who received risperidone or olanzapine therapy during the time under study.

Patients And Methods: Our study involved a sample of 751 patients diagnosed with AD and treated with anti-dementia drugs. Of the total number, 10.2% (n = 77) and 7.7% (n = 58) had been treated with risperidone and olanzapine, respectively, at some time during the follow-up. Twelve (1.6%) had received both substances in different periods of time.

Results: Mean follow-up time was 27.52 +/- 12.15 months. Mortality rate stood at 14% (n = 105). The mean maximum dose of olanzapine was 4.3 mg/day (standard deviation, SD = 2.55; range = 2.5-15) and 1.36 mg/day (SD = 0.67; range = 0.25-3.5) in the case of risperidone. Treatment lasted 519.12 (SD = 285.2; range = 90-1045) and 481.68 (SD = 345.22; range = 1-1650) days, respectively. If age, sex, conduct disorders on the Blessed scale, the cumulative heart disease index and the global deterioration scale are included in the model, both olanzapine (relative risk, RR = 8.95; confidence interval, CI 95% = 2.856-28.046) and risperidone (RR = 4.526; CI 95% = 1.816-11.281) increase the risk of death. An interaction between a history of heart disease and risperidone is recorded, which suggests a possible protection of the drug in this group. No evidence was found of an interaction between the two drugs and MS.

Conclusions: Neither the presence of cardiac disorders nor MS allow us to explain the increased mortality rate in patients with dementia who are treated with olanzapine or risperidone.

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