Statins Therapy For The Mild To Moderate Alzheimer’s Disease:a Meta-analysis Of Randomized Placebo-controlled Trials

Purpose:To assess the efficacy of3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) for the treatment of the mild to moderate Alzheimer’s disease.Search methods:We searched the Cochrane Central Register of Controlled Trials (August2012). EMBASE database (August2012) and China Biology Medicine disc,(CBM disc, August2012) systematically for the relative randomized controlled clinical trials both in English and Chinese.Included criteria:1. randomized controlled clinical trials;2. patients with mild to moderate Alzheimer’s disease;3. long-term more than6months.Excluded criteria:1. non-randomized controlled clinical trials;2. patients with no or severe Alzheimer’s disease;3. Trials compared between two different statins without a placebo.Data collection and analysis:Two reviewers independently identified studies, extracted data, and assessed the methodological quality of the studies according to the inclusion criteria. The suitable data were collected into our meta-analysis.Main results:Four randomized clinical trials, including1,078patients who received either a statin (531patients) or a placebo (547patients) with a mild to moderate Alzheimer’s disease, which were included as part of the research study. The primary outcomes were the changes in the Alzheimer’s disease Assessment Scale-cognitive portion (ADAS-Cog) and Mini Mental State Examination (MMSE) in the4trials. All the values were provided in the pattern of mean difference (MD)±standard deviation (SD). We did two subgroup analyses for the high heterogeneity:only taking statins and different statins. Overall, among the1,078patients, there is no protective effect of statins seen from the random effects model in ADAS-Cog (MD0.98,95%CI-0.87,2.83, P=0.30), MMSE (MD0.82,95%CI-0.30,1.95, P=0.15) and NPI (MD-1.41,95%CI-3.47,0.65, P=0.18). A significant benefit was seen after excluding LEADe2010with ADAS-Cog (MD1.79,95%CI0.15,3.43, P=0.30), but not in MMSE (MD1.33,95%CI-0.83,3.50, P=0.23). And no benefit was observed in the simvastatin group with ADAS-Cog (MD1.24,95%CI-0.45,2.92, P=0.15) and MMSE (MD1.28,95%CI-2.41,4.98, P=0.50) and in the atorvastatin group with ADAS-Cog (MD1.50,95%CI-3.06,6.05, P=0.52) and MMSE (MD0.77,95%CI-0.57,2.10, P=0.26).Conclusion:This meta-analysis suggests that statins treatment is not effective for the mild to moderate Alzheimer’s disease. However, the number of studies included in this review is limited. More researches are needed.