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

Sun Y, Wang G, Pan Z, Chen S - Neural Regen Res (2012)

Bottom Line: Clinical efficacy, safety, withdrawal from the studies, and withdrawal due to adverse effects.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Gerontology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Results of Mini Mental State Examination between atorvastatin (80 mg/d) and placebo for treatment of mild to moderate Alzheimer's disease. There was no statistical difference at 24 or 52 weeks between atorvastatin and placebo (P > 0.05).
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Figure 4: Results of Mini Mental State Examination between atorvastatin (80 mg/d) and placebo for treatment of mild to moderate Alzheimer's disease. There was no statistical difference at 24 or 52 weeks between atorvastatin and placebo (P > 0.05).

Mentions: Cognitive function detection: Both studies used ADAS-cog and MMSE as cognitive function measures. The random effects model was used, because there was statistical heterogeneity in these studies. There was no evidence of benefit associated with atorvastatin use on ADAS-cog or MMSE (Figures 3, 4). When the data from Sparks et al[7] was excluded from the sensitivity analyses, there was no substantial change in the results. ADAS-cog: WMD = 1.05, 95%CI: –3.06 to 6.05. MMSE: at 24 weeks, WMD = –0.52, 95%CI: –0.51 to 1.55; at 52 weeks, WMD = 0.77, 95%CI: –0.57 to 2.10.


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

Sun Y, Wang G, Pan Z, Chen S - Neural Regen Res (2012)

Results of Mini Mental State Examination between atorvastatin (80 mg/d) and placebo for treatment of mild to moderate Alzheimer's disease. There was no statistical difference at 24 or 52 weeks between atorvastatin and placebo (P > 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4308807&req=5

Figure 4: Results of Mini Mental State Examination between atorvastatin (80 mg/d) and placebo for treatment of mild to moderate Alzheimer's disease. There was no statistical difference at 24 or 52 weeks between atorvastatin and placebo (P > 0.05).
Mentions: Cognitive function detection: Both studies used ADAS-cog and MMSE as cognitive function measures. The random effects model was used, because there was statistical heterogeneity in these studies. There was no evidence of benefit associated with atorvastatin use on ADAS-cog or MMSE (Figures 3, 4). When the data from Sparks et al[7] was excluded from the sensitivity analyses, there was no substantial change in the results. ADAS-cog: WMD = 1.05, 95%CI: –3.06 to 6.05. MMSE: at 24 weeks, WMD = –0.52, 95%CI: –0.51 to 1.55; at 52 weeks, WMD = 0.77, 95%CI: –0.57 to 2.10.

Bottom Line: Clinical efficacy, safety, withdrawal from the studies, and withdrawal due to adverse effects.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Gerontology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus