Use of statins and the risk of dementia and mild cognitive impairment: A systematic review and meta-analysis

doi:10.1038/s41598-018-24248-8

Meta-Analysis

. 2018 Apr 11;8(1):5804.

doi: 10.1038/s41598-018-24248-8.

Use of statins and the risk of dementia and mild cognitive impairment: A systematic review and meta-analysis

Che-Sheng Chu^{1

2}, Ping-Tao Tseng^{3

4}, Brendon Stubbs^{5

6

7}, Tien-Yu Chen^{8

9}, Chia-Hung Tang¹⁰, Dian-Jeng Li^{11

12}, Wei-Cheng Yang¹³, Yen-Wen Chen¹⁴, Ching-Kuan Wu², Nicola Veronese¹⁵, Andre F Carvalho^{16

17}, Brisa S Fernandes^{18

19}, Nathan Herrmann²⁰, Pao-Yen Lin^{21

22}

Affiliations

¹ Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
² Center for Geriatric and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
³ Department of Psychiatry, Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai's Home, Kaohsiung, Taiwan.
⁴ WinShine Clinics in Specialty of Psychiatry, Kaohsiung, Taiwan.
⁵ Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, UK.
⁶ Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, De Crespigny Park, London, UK.
⁷ Faculty of Health, Social Care and Education, Anglia Ruskin University, Chelmsford, UK.
⁸ Department of Psychiatry, Tri-Service General Hospital; School of Medicine, National Defense Medical Center, Taipei, Taiwan.
⁹ Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan.
¹⁰ Department of Psychiatry, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan.
¹¹ Department of Addiction Science, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung, Taiwan.
¹² Graduate institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹³ Department of Adult Psychiatry, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung, Taiwan.
¹⁴ Prospect clinic for otorhinolaryngology & neurology, Kaohsiung, Taiwan.
¹⁵ National Research Council, Neuroscience Institute, Aging Branch, Padova, Italy.
¹⁶ Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
¹⁷ Centre for Addiction & Mental Health (CAMH), Toronto, ON, Canada.
¹⁸ IMPACT Strategic Research Centre, School of Medicine, and Barwon Health, Deakin University, Geelong, Australia.
¹⁹ Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto, Alegre, Brazil.
²⁰ Neuropsychopharmacology Research Group, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
²¹ Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. py1029@adm.cgmh.org.tw.
²² Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. py1029@adm.cgmh.org.tw.

PMID: 29643479
PMCID: PMC5895617
DOI: 10.1038/s41598-018-24248-8

Meta-Analysis

Use of statins and the risk of dementia and mild cognitive impairment: A systematic review and meta-analysis

Che-Sheng Chu et al. Sci Rep. 2018.

. 2018 Apr 11;8(1):5804.

doi: 10.1038/s41598-018-24248-8.

Authors

Affiliations

¹ Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
² Center for Geriatric and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
³ Department of Psychiatry, Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai's Home, Kaohsiung, Taiwan.
⁴ WinShine Clinics in Specialty of Psychiatry, Kaohsiung, Taiwan.
⁵ Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, UK.
⁶ Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, De Crespigny Park, London, UK.
⁷ Faculty of Health, Social Care and Education, Anglia Ruskin University, Chelmsford, UK.
⁸ Department of Psychiatry, Tri-Service General Hospital; School of Medicine, National Defense Medical Center, Taipei, Taiwan.
⁹ Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan.
¹⁰ Department of Psychiatry, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan.
¹¹ Department of Addiction Science, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung, Taiwan.
¹² Graduate institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹³ Department of Adult Psychiatry, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung, Taiwan.
¹⁴ Prospect clinic for otorhinolaryngology & neurology, Kaohsiung, Taiwan.
¹⁵ National Research Council, Neuroscience Institute, Aging Branch, Padova, Italy.
¹⁶ Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
¹⁷ Centre for Addiction & Mental Health (CAMH), Toronto, ON, Canada.
¹⁸ IMPACT Strategic Research Centre, School of Medicine, and Barwon Health, Deakin University, Geelong, Australia.
¹⁹ Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto, Alegre, Brazil.
²⁰ Neuropsychopharmacology Research Group, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
²¹ Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. py1029@adm.cgmh.org.tw.
²² Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. py1029@adm.cgmh.org.tw.

PMID: 29643479
PMCID: PMC5895617
DOI: 10.1038/s41598-018-24248-8

Abstract

We conducted a systematic review and meta-analysis to investigate whether the use of statins could be associated with the risk of all-caused dementia, Alzheimer's disease (AD), vascular dementia (VaD), and mild cognitive impairment (MCI). Major electronic databases were searched until December 27^th, 2017 for studies investigating use of statins and incident cognitive decline in adults. Random-effects meta-analyses calculating relative risks (RRs) were conducted to synthesize effect sizes of individual studies. Twenty-five studies met eligibility criteria. Use of statins was significantly associated with a reduced risk of all-caused dementia (k = 16 studies, adjusted RR (aRR) = 0.849, 95% CI = 0.787-0.916, p = 0.000), AD (k = 14, aRR = 0.719, 95% CI = 0.576-0.899, p = 0.004), and MCI (k = 6, aRR = 0.737, 95% CI = 0.556-0.976, p = 0.033), but no meaningful effects on incident VaD (k = 3, aRR = 1.012, 95% CI = 0.620-1.652, p = 0.961). Subgroup analysis suggested that hydrophilic statins were associated with reduced risk of all-caused dementia (aRR = 0.877; CI = 0.818-0.940; p = 0.000) and possibly lower AD risk (aRR = 0.619; CI = 0.383-1.000; p = 0.050). Lipophilic statins were associated with reduced risk of AD (aRR = 0.639; CI = 0.449-0.908; p = 0.013) but not all-caused dementia (aRR = 0.738; CI = 0.475-1.146; p = 0.176). In conclusion, our meta-analysis suggests that the use of statins may reduce the risk of all-type dementia, AD, and MCI, but not of incident VaD.

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Conflict of interest statement

The authors declare no competing interests.

Figures

**Figure 1**
PRISMA flowchart of study selection for the current systematic review and meta-analysis.

**Figure 2**
Forest plot of random-effects meta-analyses of the use of statins and incidence of all-caused dementia.

**Figure 3**
Subgroup analyses. (A) The use of hydrophilic compared to lipophilic statins and incident all-caused dementia; (B) current versus former statins users and incident all-caused dementia; and (C)The use of hydrophilic compared to lipophilic statins and incident Alzheimer’s Disease. Squares depict individual studies and diamonds depict summary effect size estimates (aRRs).

**Figure 4**
Forest plot of random-effects meta-analyses of the use of statins and incidence of (A) Alzheimer’s Disease, (B) Vascular dementia, and (C) Mild cognitive impairment. Squares depict individual studies and diamonds depict pooled effect sizes (aRRs).

See this image and copyright information in PMC

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References

1. Prince M, et al. Recent global trends in the prevalence and incidence of dementia, and survival with dementia. Alzheimers Res Ther. 2016;8:23. doi: 10.1186/s13195-016-0188-8. - DOI - PMC - PubMed
1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed (1994).
1. Wimo A, et al. The worldwide costs of dementia 2015 and comparisons with 2010. Alzheimers Dement. 2017;13:1–7. doi: 10.1016/j.jalz.2016.07.150. - DOI - PMC - PubMed
1. Shah H, et al. Research priorities to reduce the global burden of dementia by 2025. Lancet Neurol. 2016;15:1285–1294. doi: 10.1016/S1474-4422(16)30235-6. - DOI - PubMed
1. McGuinness B, Passmore P. Can statins prevent or help treat Alzheimer’s disease? J Alzheimers Dis. 2010;20:925–933. doi: 10.3233/JAD-2010-091570. - DOI - PubMed

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[1] Prince M, et al. Recent global trends in the prevalence and incidence of dementia, and survival with dementia. Alzheimers Res Ther. 2016;8:23. doi: 10.1186/s13195-016-0188-8. - DOI - PMC - PubMed

[2] Prince M, et al. Recent global trends in the prevalence and incidence of dementia, and survival with dementia. Alzheimers Res Ther. 2016;8:23. doi: 10.1186/s13195-016-0188-8. - DOI - PMC - PubMed

[3] American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed (1994).

[4] American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed (1994).

[5] Wimo A, et al. The worldwide costs of dementia 2015 and comparisons with 2010. Alzheimers Dement. 2017;13:1–7. doi: 10.1016/j.jalz.2016.07.150. - DOI - PMC - PubMed

[6] Wimo A, et al. The worldwide costs of dementia 2015 and comparisons with 2010. Alzheimers Dement. 2017;13:1–7. doi: 10.1016/j.jalz.2016.07.150. - DOI - PMC - PubMed

[7] Shah H, et al. Research priorities to reduce the global burden of dementia by 2025. Lancet Neurol. 2016;15:1285–1294. doi: 10.1016/S1474-4422(16)30235-6. - DOI - PubMed

[8] Shah H, et al. Research priorities to reduce the global burden of dementia by 2025. Lancet Neurol. 2016;15:1285–1294. doi: 10.1016/S1474-4422(16)30235-6. - DOI - PubMed

[9] McGuinness B, Passmore P. Can statins prevent or help treat Alzheimer’s disease? J Alzheimers Dis. 2010;20:925–933. doi: 10.3233/JAD-2010-091570. - DOI - PubMed

[10] McGuinness B, Passmore P. Can statins prevent or help treat Alzheimer’s disease? J Alzheimers Dis. 2010;20:925–933. doi: 10.3233/JAD-2010-091570. - DOI - PubMed

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Use of statins and the risk of dementia and mild cognitive impairment: A systematic review and meta-analysis

Affiliations

Use of statins and the risk of dementia and mild cognitive impairment: A systematic review and meta-analysis

Authors

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Abstract

Conflict of interest statement

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