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Published in: Neurological Sciences 6/2020

01-06-2020 | Atorvastatin | Review Article

The efficacy of statins in the treatment of Alzheimer’s disease: a meta-analysis of randomized controlled trial

Authors: Kun Xuan, Tianming Zhao, Guangbo Qu, Haixia Liu, Xin Chen, Yehuan Sun

Published in: Neurological Sciences | Issue 6/2020

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Abstract

Objective

Alzheimer’s disease (AD) is a common type of dementia, which has caused heavy global economic and health burden, and the using of statins to treat AD has caused widely debated. The purpose of this meta-analysis is to explore the effect of statins in the treatment of Alzheimer’s disease.

Methods

Studies were retrieved by searching PubMed, Embase, Cochrane library, OvisdSP, Web of Science, Chinese Nation Knowledge Infrastructure (CNKI) and Chinese Biomedical Database (CBM) databases before March 31, 2019. We extracted the Mini-Mental State Examination (MMSE), Alzheimer’s Disease Assessment Scale-cognitive (ADAS-Cog), Neuropsychiatric Inventory (NPI), Activities of Daily Living (ADL) scale score, and other information. The pooled Weighted Mean Difference (WMD) and their 95% confidence intervals (95% CI) were calculated with random effect model or fixed random effect model.

Results

A total of nine randomized controlled trials were included that contained 1489 patients; of them, 742 patients in the statins group, 747 patients in the control group. There were nine studies used the MMSE scale, five studies used the ADAS-Cog scale, four studies used the NPI scale, and six studies used the ADL scale. Meta-analysis of the nine studies that reported the MMSE scale scores indicated that there is no significant effect of statins as compared with control group (the pooled WMD = 1.09, 95% CI, − 0.00, 2.18, p = 0.05, I2 = 87.9%). Meta-analysis of the five studies that reported the ADAS-Cog scale scores also indicated that there is no significant effect of statins as compared with control group (the pooled WMD = − 0.16, 95% CI, − 2.67, 2.36, p = 0.90, I2 = 80.1%). Meta-analysis of the four studies that reported the NPI scale scores indicated that treatment with statins could slow the rise in the NPI scale scores (the pooled WMD = − 1.16, 95% CI, − 1.88, − 0.44, p = 0.002, I2 = 45.4%). Meta-analysis of the six studies that reported the ADL scale scores indicated that treatment with statins could improve patients’ daily living ability (the pooled WMD = − 4.06, 95% CI, − 6.88, − 1.24, p = 0.005, I2 = 86.7%). Results of subgroup analysis indicated that the use of statins in the short term (≤ 12 months) associated with the change of the MMSE scale scores (the pooled WMD = 1.78, 95% CI, 0.53, 3.04, p = 0.005, I2 = 79.6%). Sensitivity analysis and publication bias test were both negative, and the results were relatively reliable and stable.

Conclusion

Statins used in AD patients had beneficial effects on the scores of MMSE scale in the short term (≤ 12 months), and statins could slow the deterioration of neuropsychiatric status and significantly improve activities of daily living ability in AD patients, but statins did not show an advantage in the change of the ADAS-Cog scale scores.
Literature
3.
go back to reference Prince M, Comas-Herrera A, Knapp M, Guerchet M, Karagiannidou M (2016) World Alzheimer report 2016: improving healthcare for people living with dementia: coverage, quality and costs now and in the future. Alzheimer’s Disease International (ADI), London Prince M, Comas-Herrera A, Knapp M, Guerchet M, Karagiannidou M (2016) World Alzheimer report 2016: improving healthcare for people living with dementia: coverage, quality and costs now and in the future. Alzheimer’s Disease International (ADI), London
5.
6.
go back to reference Jia J, Wei C, Chen S, Li F, Tang Y, Qin W, Zhao L, Jin H, Xu H, Wang F, Zhou A, Zuo X, Wu L, Han Y, Han Y, Huang L, Wang Q, Li D, Chu C, Shi L, Gong M, Du Y, Zhang J, Zhang J, Zhou C, Lv J, Lv Y, Xie H, Ji Y, Li F, Yu E, Luo B, Wang Y, Yang S, Qu Q, Guo Q, Liang F, Zhang J, Tan L, Shen L, Zhang K, Zhang J, Peng D, Tang M, Lv P, Fang B, Chu L, Jia L, Gauthier S (2018) The cost of Alzheimer’s disease in China and re-estimation of costs worldwide. Alzheimers Dement 14(4):483–491. https://doi.org/10.1016/j.jalz.2017.12.006 CrossRefPubMed Jia J, Wei C, Chen S, Li F, Tang Y, Qin W, Zhao L, Jin H, Xu H, Wang F, Zhou A, Zuo X, Wu L, Han Y, Han Y, Huang L, Wang Q, Li D, Chu C, Shi L, Gong M, Du Y, Zhang J, Zhang J, Zhou C, Lv J, Lv Y, Xie H, Ji Y, Li F, Yu E, Luo B, Wang Y, Yang S, Qu Q, Guo Q, Liang F, Zhang J, Tan L, Shen L, Zhang K, Zhang J, Peng D, Tang M, Lv P, Fang B, Chu L, Jia L, Gauthier S (2018) The cost of Alzheimer’s disease in China and re-estimation of costs worldwide. Alzheimers Dement 14(4):483–491. https://​doi.​org/​10.​1016/​j.​jalz.​2017.​12.​006 CrossRefPubMed
10.
go back to reference Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, Ford I, Gaw A, Hyland M, Jukema JW, Kamper AM, Macfarlane PW, Meinders AE, Norrie J, Packard CJ, Perry IJ, Stott DJ, Sweeney BJ, Twomey C, Westendorp RG (2002) Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 360(9346):1623–1630. https://doi.org/10.1016/S0140-6736(02)11600-X CrossRefPubMed Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, Ford I, Gaw A, Hyland M, Jukema JW, Kamper AM, Macfarlane PW, Meinders AE, Norrie J, Packard CJ, Perry IJ, Stott DJ, Sweeney BJ, Twomey C, Westendorp RG (2002) Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 360(9346):1623–1630. https://​doi.​org/​10.​1016/​S0140-6736(02)11600-X CrossRefPubMed
29.
30.
go back to reference Pandey R, Jha D, Pandey P, Gupta P, Shah V (2017) An indirect treatment comparison of unapproved treatment options of Alzheimer's disease for research prioritization. Value Health 20(5): A311-A312. Pandey R, Jha D, Pandey P, Gupta P, Shah V (2017) An indirect treatment comparison of unapproved treatment options of Alzheimer's disease for research prioritization. Value Health 20(5): A311-A312.
35.
go back to reference Sparks DL, Sabbagh MN, Connor DJ, Lopez J, Launer LJ, Petanceska S, Browne P, Wassar D, Johnson-Traver S, Lochhead J, Ziolkowski C (2005) Atorvastatin therapy lowers circulating cholesterol but not free radical activity in advance of identifiable clinical benefit in the treatment of mild-to-moderate AD. Curr Alzheimer Res 2(3):343–353. https://doi.org/10.2174/1567205054367900 CrossRefPubMed Sparks DL, Sabbagh MN, Connor DJ, Lopez J, Launer LJ, Petanceska S, Browne P, Wassar D, Johnson-Traver S, Lochhead J, Ziolkowski C (2005) Atorvastatin therapy lowers circulating cholesterol but not free radical activity in advance of identifiable clinical benefit in the treatment of mild-to-moderate AD. Curr Alzheimer Res 2(3):343–353. https://​doi.​org/​10.​2174/​1567205054367900​ CrossRefPubMed
37.
go back to reference Simons M, Schwarzler F, Lutjohann D, von Bergmann K, Beyreuther K, Dichgans J, Wormstall H, Hartmann T, Schulz JB (2002) Treatment with simvastatin in normocholesterolemic patients with Alzheimer’s disease: a 26-week randomized, placebo-controlled, double-blind trial. Ann Neurol 52(3):346–350. https://doi.org/10.1002/ana.10292 CrossRefPubMed Simons M, Schwarzler F, Lutjohann D, von Bergmann K, Beyreuther K, Dichgans J, Wormstall H, Hartmann T, Schulz JB (2002) Treatment with simvastatin in normocholesterolemic patients with Alzheimer’s disease: a 26-week randomized, placebo-controlled, double-blind trial. Ann Neurol 52(3):346–350. https://​doi.​org/​10.​1002/​ana.​10292 CrossRefPubMed
38.
go back to reference Zhao XL, Liu Y, Zhang Z, Zeng Z, Gao L, Yang X, Deng X, Zhu X (2010) Effect and safety of atrovastatin combined with memantine with moderate to severe Alzheimer’s disease. Chin J Pract Nerv Dis 21:9–11 Zhao XL, Liu Y, Zhang Z, Zeng Z, Gao L, Yang X, Deng X, Zhu X (2010) Effect and safety of atrovastatin combined with memantine with moderate to severe Alzheimer’s disease. Chin J Pract Nerv Dis 21:9–11
39.
go back to reference Zhao XL, Liu Y (2011) Effect of Donepezil and Atrovastatin on moderate or severe Alzheimer disease and its safety. Pract J Clin Med 3:52–54 Zhao XL, Liu Y (2011) Effect of Donepezil and Atrovastatin on moderate or severe Alzheimer disease and its safety. Pract J Clin Med 3:52–54
48.
go back to reference Cummings JL (1997) The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology 48(5 Suppl 6):S10–S16CrossRefPubMed Cummings JL (1997) The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology 48(5 Suppl 6):S10–S16CrossRefPubMed
52.
go back to reference Carlsson CM, Gleason CE, Hess TM, Moreland KA, Blazel HM, Koscik RL, Schreiber NT, Johnson SC, Atwood CS, Puglielli L, Hermann BP, McBride PE, Stein JH, Sager MA, Asthana S (2008) Effects of simvastatin on cerebrospinal fluid biomarkers and cognition in middle-aged adults at risk for Alzheimer’s disease. J Alzheimers Dis 13(2):187–197CrossRefPubMed Carlsson CM, Gleason CE, Hess TM, Moreland KA, Blazel HM, Koscik RL, Schreiber NT, Johnson SC, Atwood CS, Puglielli L, Hermann BP, McBride PE, Stein JH, Sager MA, Asthana S (2008) Effects of simvastatin on cerebrospinal fluid biomarkers and cognition in middle-aged adults at risk for Alzheimer’s disease. J Alzheimers Dis 13(2):187–197CrossRefPubMed
53.
go back to reference Chan D, Binks S, Nicholas JM, Frost C, Cardoso MJ, Ourselin S, Wilkie D, Nicholas R, Chataway J (2017) Effect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebo-controlled trial. Lancet Neurol 16(8):591–600. https://doi.org/10.1016/s1474-4422(17)30113-8 CrossRefPubMedPubMedCentral Chan D, Binks S, Nicholas JM, Frost C, Cardoso MJ, Ourselin S, Wilkie D, Nicholas R, Chataway J (2017) Effect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebo-controlled trial. Lancet Neurol 16(8):591–600. https://​doi.​org/​10.​1016/​s1474-4422(17)30113-8 CrossRefPubMedPubMedCentral
61.
62.
go back to reference Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science (New York, NY) 261(5123):921–923. https://doi.org/10.1126/science.8346443 CrossRef Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science (New York, NY) 261(5123):921–923. https://​doi.​org/​10.​1126/​science.​8346443 CrossRef
Metadata
Title
The efficacy of statins in the treatment of Alzheimer’s disease: a meta-analysis of randomized controlled trial
Authors
Kun Xuan
Tianming Zhao
Guangbo Qu
Haixia Liu
Xin Chen
Yehuan Sun
Publication date
01-06-2020
Publisher
Springer International Publishing
Published in
Neurological Sciences / Issue 6/2020
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-020-04243-6

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