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January 16, 2018; 90 (3) Article

Comparative effect of statins on the risk of incident Alzheimer disease

Liliya Sinyavskaya, Serge Gauthier, Christel Renoux, Sophie Dell'Aniello, Samy Suissa, Paul Brassard
First published December 15, 2017, DOI: https://doi.org/10.1212/WNL.0000000000004818
Liliya Sinyavskaya
From the Centre for Clinical Epidemiology (L.S., C.R., S.D., S.S., P.B.), Jewish General Hospital; McGill University Research Centre for Studies in Aging (S.G.), Douglas Mental Health University Institute; and Departments of Neurology and Neurosurgery (C.R.) and Medicine and Epidemiology, Biostatistics, and Occupational Health (C.R., S.S., P.B.), McGill University, Montreal, Canada.
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Serge Gauthier
From the Centre for Clinical Epidemiology (L.S., C.R., S.D., S.S., P.B.), Jewish General Hospital; McGill University Research Centre for Studies in Aging (S.G.), Douglas Mental Health University Institute; and Departments of Neurology and Neurosurgery (C.R.) and Medicine and Epidemiology, Biostatistics, and Occupational Health (C.R., S.S., P.B.), McGill University, Montreal, Canada.
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Christel Renoux
From the Centre for Clinical Epidemiology (L.S., C.R., S.D., S.S., P.B.), Jewish General Hospital; McGill University Research Centre for Studies in Aging (S.G.), Douglas Mental Health University Institute; and Departments of Neurology and Neurosurgery (C.R.) and Medicine and Epidemiology, Biostatistics, and Occupational Health (C.R., S.S., P.B.), McGill University, Montreal, Canada.
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Sophie Dell'Aniello
From the Centre for Clinical Epidemiology (L.S., C.R., S.D., S.S., P.B.), Jewish General Hospital; McGill University Research Centre for Studies in Aging (S.G.), Douglas Mental Health University Institute; and Departments of Neurology and Neurosurgery (C.R.) and Medicine and Epidemiology, Biostatistics, and Occupational Health (C.R., S.S., P.B.), McGill University, Montreal, Canada.
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Samy Suissa
From the Centre for Clinical Epidemiology (L.S., C.R., S.D., S.S., P.B.), Jewish General Hospital; McGill University Research Centre for Studies in Aging (S.G.), Douglas Mental Health University Institute; and Departments of Neurology and Neurosurgery (C.R.) and Medicine and Epidemiology, Biostatistics, and Occupational Health (C.R., S.S., P.B.), McGill University, Montreal, Canada.
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Paul Brassard
From the Centre for Clinical Epidemiology (L.S., C.R., S.D., S.S., P.B.), Jewish General Hospital; McGill University Research Centre for Studies in Aging (S.G.), Douglas Mental Health University Institute; and Departments of Neurology and Neurosurgery (C.R.) and Medicine and Epidemiology, Biostatistics, and Occupational Health (C.R., S.S., P.B.), McGill University, Montreal, Canada.
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Citation
Comparative effect of statins on the risk of incident Alzheimer disease
Liliya Sinyavskaya, Serge Gauthier, Christel Renoux, Sophie Dell'Aniello, Samy Suissa, Paul Brassard
Neurology Jan 2018, 90 (3) e179-e187; DOI: 10.1212/WNL.0000000000004818

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Abstract

Objective To investigate whether fungus-derived statins are associated with a lower risk of incident Alzheimer disease (AD) compared with synthetic statins using real-world clinical practice data.

Methods We identified a population-based retrospective cohort of patients aged ≥60 years newly prescribed a statin between January 1, 1994, and December 31, 2012, and followed until March 31, 2015, using the UK Clinical Practice Research Datalink. Statins were consecutively classified according to their type, lipophilicity, and potency. For each group, we calculated the crude AD incidence rates per 1,000 person-years. Time-dependent Cox proportional hazards models adjusted for propensity score deciles were used to estimate hazard ratios (HRs) with 95% confidence interval (CIs) of incident AD associated with different statin categories.

Results Over the 18-year study period, we identified 465,085 statin users, including 7,669 patients who developed AD during 2,891,268 person-years of follow-up (incidence rate 2.65 [95% CI 2.59–2.71] per 1,000 person-years). Compared to synthetic, fungus-derived statins were associated with an increased risk of AD (HR 1.09, 95% CI 1.03–1.15). Lipophilic statins also were associated with higher AD risk (HR 1.18, 95% CI 1.09–1.27) compared to hydrophilic statins, while statin potency did not modify the risk of AD (adjusted HR 1.03, 95% CI 0.98–1.08). The risk was further reduced in sensitivity analyses.

Conclusion Fungus-derived and lipophilic statins were not associated with decreased incidence of AD compared to synthetic and hydrophilic statins. The modest variations in the risk of incident AD observed between statin characteristics needs to be evaluated in future studies on their possible heterogeneous neuroprotective effect.

Glossary

AD=
Alzheimer disease;
CI=
confidence interval;
CPRD=
UK Clinical Practice Research Datalink;
HR=
hazard ratio;
IQR=
interquartile range;
LLD=
lipid-lowering drug;
PS=
propensity score;
UTS=
up-to-standard

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received February 20, 2017.
  • Accepted in final form September 19, 2017.
  • Copyright © 2017 American Academy of Neurology
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