Systematic review of atorvastatin for the treatment of Alzheimer's disease★

OBJECTIVE: To assess the clinical efficacy and safety of atorvastatin in the treatment of Alzheimer's disease. DATA SOURCES: Medline (1948/2011-04), Embase (1966/2011-04), Cochrane Library (Issue 3, 2011), Chinese National Knowledge Infrastructure (1989/2011-04), and the Chinese Biomedical Literature Database (1979/2011-04) were searched for randomized clinical trials regardless of language. Abstracts of conference papers were manually searched. Furthermore, Current Controlled Trials (http://controlled-trials.com), Clinical Trials.gov (http://clinicaltrials.gov), and Chinese Clinical Trial Registry (http://www.chictr.org) were also searched. Key words included Alzheimer disease, dementia, cognition, affection, memory dysfunction, hydroxymethylglutaryl-CoA reductase inhibitors, atorvastatin and statins. DATA SELECTION: Randomized controlled trials of grade A or B according to quality evaluation criteria of the Cochrane Collaboration were selected, in which atorvastatin and placebo were used to evaluate the effects of atorvastatin in the treatment of Alzheimer's disease. Study methodological quality was evaluated based on criteria described in Cochrane Reviewer's Handbook 5.0.1. Revman 5.1 software was used for data analysis. MAIN OUTCOME MEASURES: Clinical efficacy, safety, withdrawal from the studies, and withdrawal due to adverse effects. RESULTS: Two randomized controlled trials were included, one was scale A, and the other was scale B. All patients (n = 710, age range 50–90 years) were diagnosed as probable or possible mild to moderate Alzheimer's disease according to standard criteria and treated with atorvastatin 80 mg/d or placebo. There was no difference between the two groups in the final follow-up for Clinical Global Impression of Change scale (WMD = 0.13, 95%CI: –0.15 to 0.40), the Alzheimer's Disease Assessment Scale-cognitive subscale (WMD = 1.05, 95%CI: –3.06 to 6.05), Mini-Mental State Examination Scale (WMD = 0.77, 95%CI: –0.57 to 2.10), and the Neuropsychiatric Instrument (WMD = 2.07, 95%CI: –1.59 to 5.73). The rates of abnormal liver function, withdrawal from treatment, and withdrawal due to adverse effects were higher in the treatment group (OR = 7.86, 95%CI: 2.50-24.69; OR = 4.70, 95%CI: 2.61-8.44; and OR = 5.47, 95%CI: 3.01-9.94; respectively) compared with the placebo group. CONCLUSION: There is insufficient evidence to recommend atorvastatin for the treatment of mild to moderate Alzheimer's disease, because there was no benefit on general function, cognitive function or mental/behavior abnormality outcome measures. Efficacy and safety need to be confirmed by larger and higher quality randomized controlled trials, especially for moderate to severe Alzheimer's disease, because results of this systematic review may be limited by selection bias, implementation bias, as well as measurement bias.