Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Statins, cognition, and dementia—systematic review and methodological commentary

Nature Reviews Neurology volume 11, pages 220–229 (2015)Cite this article

Subjects

Key Points

  • Initiation of statin use in late life does not seem to prevent cognitive decline and dementia over the subsequent few years

  • The current literature does not address whether mid-life or long-term statin use has beneficial effects on subsequent cognition

  • Many studies that assessed time-updated statin use suggest a protective effect of statin use on cognitive decline, but these findings are probably attributable to reverse causation

  • Ethical and feasibility considerations limit randomized controlled trials; carefully designed observational studies that use appropriate analytical methods are our best hope for determining the effects of statin use on cognition

  • Future observational work must incorporate study designs and analytical techniques that minimize the potential for bias, especially that which is due to reverse causation and confounding

Abstract

Firm conclusions about whether mid-life or long-term statin use has an impact on cognitive decline and dementia remain elusive. Here, our objective was to systematically review, synthesize and critique the epidemiological literature that examines the relationship between statin use and cognition, so as to assess the current state of knowledge, identify gaps in our understanding, and make recommendations for future research. We summarize the findings of randomized controlled trials (RCTs) and observational studies, grouped according to study design. We discuss the methods for each, and consider likely sources of bias, such as reverse causation and confounding. Although observational studies that considered statin use at or near the time of dementia diagnosis suggest a protective effect of statins, these findings could be attributable to reverse causation. RCTs and well-conducted observational studies of baseline statin use and subsequent cognition over several years of follow-up do not support a causal preventative effect of late-life statin use on cognitive decline or dementia. Given that much of the human research on statins and cognition in the future will be observational, careful study design and analysis will be essential.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Flow diagram of the study selection process for the systematic review.
Figure 2: Reverse causation in analyses that consider statin use and dementia risk.
Figure 3: Interpretation of survival models using time-updated current or never–ever statin use with no lag.
Figure 4: Time-dependent confounding.

Similar content being viewed by others

References

  1. Stone, N. J. et al. 2013 ACC/AHA Guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 129 (25 Suppl. 2), S1–S45 (2014).

    Article  PubMed  Google Scholar 

  2. Pencina, M. J. et al. Application of new cholesterol guidelines to a population-based sample. New Engl. J. Med. 370, 1422–1431 (2014).

    Article  CAS  PubMed  Google Scholar 

  3. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 106, 3143–3421 (2002).

  4. Grundy, S. M. et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. J. Am. Coll. Cardiol. 44, 720–732 (2004).

    Article  PubMed  Google Scholar 

  5. Naci, H. et al. Comparative benefits of statins in the primary and secondary prevention of major coronary events and all-cause mortality: a network meta-analysis of placebo-controlled and active-comparator trials. Eur. J. Prev. Cardiol. 20, 641–657 (2013).

    Article  PubMed  Google Scholar 

  6. Udell, J. A. & Ray, J. G. Primary and secondary prevention of heart failure with statins. Expert Rev. Cardiovasc. Ther. 4, 917–926 (2006).

    Article  CAS  PubMed  Google Scholar 

  7. Taylor, F. et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews, Issue 1. Art. No.: CD004816. http://dx.doi.org/10.1002/14651858.CD004816.pub4.

  8. Rojas-Fernandez, C. H. & Cameron, J. C. Is statin-associated cognitive impairment clinically relevant? A narrative review and clinical recommendations. Ann. Pharmacother. 46, 549–557 (2012).

    Article  CAS  PubMed  Google Scholar 

  9. Evans, M. A. & Golomb, B. A. Statin-associated adverse cognitive effects: survey results from 171 patients. Pharmacotherapy 29, 800–811 (2009).

    Article  CAS  PubMed  Google Scholar 

  10. FDA drug safety communication: important safety label changes to cholesterol-lowering statin drugs. U.S. Food and Drug Administration [online] (2012).

  11. Anstey, K. J., Lipnicki, D. M. & Low, L. F. Cholesterol as a risk factor for dementia and cognitive decline: a systematic review of prospective studies with meta-analysis. Am. J. Geriatr. Psychiatry 16, 343–354 (2008).

    Article  PubMed  Google Scholar 

  12. Stewart, R., White, L. R., Xue, Q. L. & Launer, L. J. Twenty-six-year change in total cholesterol levels and incident dementia: the Honolulu–Asia Aging Study. Arch. Neurol. 64, 103–107 (2007).

    Article  PubMed  Google Scholar 

  13. Panza, F. et al. Lipid metabolism in cognitive decline and dementia. Brain Res. Rev. 51, 275–292 (2006).

    Article  CAS  PubMed  Google Scholar 

  14. Gorelick, P. B. et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42, 2672–2713 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Jain, M. K. & Ridker, P. M. Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat. Rev. Drug Discov. 4, 977–987 (2005).

    Article  CAS  PubMed  Google Scholar 

  16. Miida, T., Takahashi, A. & Ikeuchi, T. Prevention of stroke and dementia by statin therapy: experimental and clinical evidence of their pleiotropic effects. Pharmacol. Ther. 113, 378–393 (2007).

    Article  CAS  PubMed  Google Scholar 

  17. Bifulco, M., Malfitano, A. M. & Marasco, G. Potential therapeutic role of statins in neurological disorders. Expert Rev. Neurother. 8, 827–837 (2008).

    Article  CAS  PubMed  Google Scholar 

  18. Sierra, S. et al. Statins as neuroprotectants: a comparative in vitro study of lipophilicity, blood–brain-barrier penetration, lowering of brain cholesterol, and decrease of neuron cell death. J. Alzheimers Dis. 23, 307–318 (2011).

    Article  CAS  PubMed  Google Scholar 

  19. Carlsson, C. M. et al. Effects of atorvastatin on cerebral blood flow in middle-aged adults at risk for Alzheimer's disease: a pilot study. Curr. Alzheimer Res. 9, 990–997 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Locatelli, S. et al. Reduction of plasma 24S-hydroxycholesterol (cerebrosterol) levels using high-dosage simvastatin in patients with hypercholesterolemia: evidence that simvastatin affects cholesterol metabolism in the human brain. Arch. Neurol. 59, 213–216 (2002).

    Article  PubMed  Google Scholar 

  21. Lutjohann, D. & von Bergmann, K. 24S-Hydroxycholesterol: a marker of brain cholesterol metabolism. Pharmacopsychiatry 36 (Suppl. 2), S102–S106 (2003).

    PubMed  Google Scholar 

  22. Serrano-Pozo, A. et al. Effects of simvastatin on cholesterol metabolism and Alzheimer disease biomarkers. Alzheimer Dis. Assoc. Disord. 24, 220–226 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Vega, G. L. et al. Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease. Arch. Neurol. 60, 510–515 (2003).

    Article  PubMed  Google Scholar 

  24. Höglund, K. & Blennow, K. Effect of HMG-CoA reductase inhibitors on β-amyloid peptide levels: implications for Alzheimer's disease. CNS Drugs 21, 449–462 (2007).

    Article  PubMed  Google Scholar 

  25. Fassbender, K. et al. Effects of statins on human cerebral cholesterol metabolism and secretion of Alzheimer amyloid peptide. Neurology 59, 1257–1258 (2002).

    Article  CAS  PubMed  Google Scholar 

  26. Höglund, K. et al. Statin treatment and a disease-specific pattern of β-amyloid peptides in Alzheimer's disease. Exp. Brain Res. 164, 205–214 (2005).

    Article  CAS  PubMed  Google Scholar 

  27. Riekse, R. G. et al. Effect of statins on Alzheimer's disease biomarkers in cerebrospinal fluid. J. Alzheimers Dis. 10, 399–406 (2006).

    Article  CAS  PubMed  Google Scholar 

  28. Arvanitakis, Z. et al. Statins, incident Alzheimer disease, change in cognitive function, and neuropathology. Neurology 70, 1795–1802 (2008).

    Article  CAS  PubMed  Google Scholar 

  29. Refolo, L. M. et al. Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. Neurobiol. Dis. 7, 321–331 (2000).

    Article  CAS  PubMed  Google Scholar 

  30. Pollen, D. A. et al. Prevention of Alzheimer's disease in high risk groups: statin therapy in subjects with PSEN1 mutations or heterozygosity for apolipoprotein Eε4. Alzheimers Res. Ther. 2, 31 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Li, G. et al. Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease. Neurology 69, 878–885 (2007).

    Article  CAS  PubMed  Google Scholar 

  32. McGuinness, B., Craig, D., Bullock, R. & Passmore, P. Statins for the prevention of dementia. Cochrane Database of Systematic Reviews, Issue 2. Art. No.: CD003160 http://dx.doi.org/10.1002/14651858.CD003160.pub2.

  33. Swiger, K. J., Manalac, R. J., Blumenthal, R. S., Blaha, M. J. & Martin, S. S. Statins and cognition: a systematic review and meta-analysis of short- and long-term cognitive effects. Mayo Clin. Proc. 88, 1213–1221 (2013).

    Article  CAS  PubMed  Google Scholar 

  34. Muangpaisan, W., Brayne, C. & Alzheimer's Society Vascular Dementia Systematic Review Group. Systematic review of statins for the prevention of vascular dementia or dementia. Geriatr. Gerontol. Int. 10, 199–208 (2010).

    PubMed  Google Scholar 

  35. Zhou, B., Teramukai, S. & Fukushima, M. Prevention and treatment of dementia or Alzheimer's disease by statins: a meta-analysis. Dement. Geriatr. Cogn. Disord. 23, 194–201 (2007).

    Article  CAS  PubMed  Google Scholar 

  36. Wong, W. B., Lin, V. W., Boudreau, D. & Devine, E. B. Statins in the prevention of dementia and Alzheimer's disease: a meta-analysis of observational studies and an assessment of confounding. Pharmacoepidemiol. Drug Saf. 22, 345–358 (2013).

    Article  CAS  PubMed  Google Scholar 

  37. Richardson, K. et al. Statins and cognitive function: a systematic review. Ann. Intern. Med. 159, 688–697 (2013).

    Article  PubMed  Google Scholar 

  38. AlzRisk methods. Alzforum [online] (2015).

  39. Glymour, M. M., Weuve, J., Berkman, L. F., Kawachi, I. & Robins, J. M. When is baseline adjustment useful in analyses of change? An example with education and cognitive change. Am. J. Epidemiol. 162, 267–278 (2005).

    Article  PubMed  Google Scholar 

  40. Carlsson, C. M. et al. Effects of simvastatin on cerebrospinal fluid biomarkers and cognition in middle-aged adults at risk for Alzheimer's disease. J. Alzheimers Dis. 13, 187–197 (2008).

    Article  CAS  PubMed  Google Scholar 

  41. Carlsson, C. M. et al. Effects of simvastatin on cerebrospinal fluid biomarkers and cognition in middle-aged adults at risk for Alzheimer's disease. J. Alzheimers Dis. 13, 187–197 (2008).

    Article  CAS  PubMed  Google Scholar 

  42. Gibellato, M. G., Moore, J. L., Selby, K. & Bower, E. A. Effects of lovastatin and pravastatin on cognitive function in military aircrew. Aviat. Space Environ. Med. 72, 805–812 (2001).

    CAS  PubMed  Google Scholar 

  43. Kostis, J. B., Rosen, R. C. & Wilson, A. C. Central nervous system effects of HMG CoA reductase inhibitors: lovastatin and pravastatin on sleep and cognitive performance in patients with hypercholesterolemia. J. Clin. Pharmacol. 34, 989–996 (1994).

    Article  CAS  PubMed  Google Scholar 

  44. Muldoon, M. F. et al. Effects of lovastatin on cognitive function and psychological well-being. Am. J. Med. 108, 538–546 (2000).

    Article  CAS  PubMed  Google Scholar 

  45. Muldoon, M. F., Ryan, C. M., Sereika, S. M., Flory, J. D. & Manuck, S. B. Randomized trial of the effects of simvastatin on cognitive functioning in hypercholesterolemic adults. Am. J. Med. 117, 823–829 (2004).

    Article  CAS  PubMed  Google Scholar 

  46. Summers, M. J., Oliver, K. R., Coombes, J. S. & Fassett, R. G. Effect of atorvastatin on cognitive function in patients from the Lipid Lowering and Onset of Renal Disease (LORD) trial. Pharmacotherapy 27, 183–190 (2007).

    Article  CAS  PubMed  Google Scholar 

  47. Trompet, S. et al. Pravastatin and cognitive function in the elderly. Results of the PROSPER study. J. Neurol. 257, 85–90 (2010).

    Article  CAS  PubMed  Google Scholar 

  48. Harrison, R. W. & Ashton, C. H. Do cholesterol-lowering agents affect brain activity? A comparison of simvastatin, pravastatin, and placebo in healthy volunteers. Br. J. Clin. Pharmacol. 37, 231–236 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Santanello, N. C. et al. Effect of pharmacologic lipid lowering on health-related quality of life in older persons: results from the Cholesterol Reduction in Seniors Program (CRISP) Pilot Study. J. Am. Geriatr. Soc. 45, 8–14 (1997).

    Article  CAS  PubMed  Google Scholar 

  50. Gengo, F. et al. Effects of treatment with lovastatin and pravastatin on daytime cognitive performance. Clin. Cardiol. 18, 209–214 (1995).

    Article  CAS  PubMed  Google Scholar 

  51. Roth, T. et al. Comparative effects of pravastatin and lovastatin on nighttime sleep and daytime performance. Clin. Cardiol. 15, 426–432 (1992).

    Article  CAS  PubMed  Google Scholar 

  52. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360, 7–22 (2002).

  53. Shepherd, J. et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 360, 1623–1630 (2002).

    Article  CAS  PubMed  Google Scholar 

  54. Cutler, N. et al. Effects of treatment with simvastatin and pravastatin on cognitive function in patients with hypercholesterolaemia. Br. J. Clin. Pharmacol. 39, 333–336 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Li, G. et al. Statin therapy and risk of dementia in the elderly: a community-based prospective cohort study. Neurology 63, 1624–1628 (2004).

    Article  CAS  PubMed  Google Scholar 

  56. Li, G. et al. Age-varying association between statin use and incident Alzheimer's disease. J. Am. Geriatr. Soc. 58, 1311–1317 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  57. Sparks, D. L. et al. Reduced risk of incident AD with elective statin use in a clinical trial cohort. Curr. Alzheimer Res. 5, 416–421 (2008).

    Article  CAS  PubMed  Google Scholar 

  58. Beydoun, M. A. et al. Statins and serum cholesterol's associations with incident dementia and mild cognitive impairment. J. Epidemiol. Community Health 65, 949–957 (2011).

    Article  PubMed  Google Scholar 

  59. Rea, T. D. et al. Statin use and the risk of incident dementia: the Cardiovascular Health Study. Arch. Neurol. 62, 1047–1051 (2005).

    Article  PubMed  Google Scholar 

  60. Bernick, C. et al. Statins and cognitive function in the elderly: the Cardiovascular Health Study. Neurology 65, 1388–1394 (2005).

    Article  CAS  PubMed  Google Scholar 

  61. Bettermann, K. et al. Statins, risk of dementia, and cognitive function: secondary analysis of the ginkgo evaluation of memory study. J. Stroke Cerebrovasc. Dis. 21, 436–444 (2012).

    Article  PubMed  Google Scholar 

  62. Szwast, S. J. et al. Association of statin use with cognitive decline in elderly African Americans. Neurology 69, 1873–1880 (2007).

    Article  CAS  PubMed  Google Scholar 

  63. Steenland, K., Zhao, L., Goldstein, F. C. & Levey, A. I. Statins and cognitive decline in older adults with normal cognition or mild cognitive impairment. J. Am. Geriatr. Soc. 61, 1449–1455 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  64. Hippisley-Cox, J. & Coupland, C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ 340, c2197 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  65. Cramer, C., Haan, M. N., Galea, S., Langa, K. M. & Kalbfleisch, J. D. Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study. Neurology 71, 344–350 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Zandi, P. P. et al. Do statins reduce risk of incident dementia and Alzheimer disease? The Cache County Study. Arch. Gen. Psychiatry 62, 217–224 (2005).

    Article  CAS  PubMed  Google Scholar 

  67. Smeeth, L., Douglas, I., Hall, A. J., Hubbard, R. & Evans, S. Effect of statins on a wide range of health outcomes: a cohort study validated by comparison with randomized trials. Br. J. Clin. Pharmacol. 67, 99–109 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  68. Haag, M. D., Hofman, A., Koudstaal, P. J., Stricker, B. H. & Breteler, M. M. Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity. The Rotterdam Study. J. Neurol. Neurosurg. Psychiatry 80, 13–17 (2009).

    Article  CAS  PubMed  Google Scholar 

  69. Starr, J. M. et al. Life long changes in cognitive ability are associated with prescribed medications in old age. Int. J. Geriatr. Psychiatry 19, 327–332 (2004).

    Article  PubMed  Google Scholar 

  70. Ancelin, M. L. et al. Lipid lowering agents, cognitive decline, and dementia: the three-city study. J. Alzheimers Dis. 30, 629–637 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Wolozin, B. et al. Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease. BMC Med. 5, 20 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Chou, C.-Y., Chou, Y.-C., Chou, Y.-J., Yang, Y.-F. & Huang, N. Statin use and incident dementia: a nationwide cohort study of Taiwan. Int. J. Cardiol. 173, 305–310 (2014).

    Article  PubMed  Google Scholar 

  73. Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G. & PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 6, e1000097 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Hernán, M. A., Hernández-Diaz, S. & Robins, J. M. A structural approach to selection bias. Epidemiology 15, 615–625 (2004).

    Article  PubMed  Google Scholar 

  75. Fox, N. C., Warrington, E. K. & Rossor, M. N. Serial magnetic resonance imaging of cerebral atrophy in preclinical Alzheimer's disease. Lancet 353, 2125 (1999).

    Article  CAS  PubMed  Google Scholar 

  76. Jack, C. R. Jr et al. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol. 9, 119–128 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Sperling, R. A. et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 7, 280–292 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  78. Power, M. C., Tchetgen, E. J., Sparrow, D., Schwartz, J. & Weisskopf, M. G. Blood pressure and cognition: factors that may account for their inconsistent association. Epidemiology 24, 886–893 (2013).

    Article  PubMed  Google Scholar 

  79. Qiu, C., Winblad, B. & Fratiglioni, L. The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol. 4, 487–499 (2005).

    Article  PubMed  Google Scholar 

  80. Paglieri, C. et al. Hypertension and cognitive function. Clin. Exp. Hypertens. 30, 701–710 (2008).

    Article  PubMed  Google Scholar 

  81. Dufouil, C. et al. APOE genotype, cholesterol level, lipid-lowering treatment, and dementia: the Three-City Study. Neurology 64, 1531–1538 (2005).

    Article  CAS  PubMed  Google Scholar 

  82. Rait, G. et al. Survival of people with clinical diagnosis of dementia in primary care: cohort study. BMJ 341, c3584 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  83. van den Dungen, P. et al. The accuracy of family physicians' dementia diagnoses at different stages of dementia: a systematic review. Int. J. Geriatr. Psychiatry 27, 342–354 (2012).

    PubMed  Google Scholar 

  84. Taylor, D. H. Jr, Østbye, T., Langa, K. M., Weir, D. & Plassman, B. L. The accuracy of Medicare claims as an epidemiological tool: the case of dementia revisited. J. Alzheimers Dis. 17, 807–815 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  85. Butler, D., Kowall, N. W., Lawler, E., Michael Gaziano, J. & Driver, J. A. Underuse of diagnostic codes for specific dementias in the Veterans Affairs New England healthcare system. J. Am. Geriatr. Soc. 60, 910–915 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  86. Brookhart, M. A. et al. Adherence to lipid-lowering therapy and the use of preventive health services: an investigation of the healthy user effect. Am. J. Epidemiol. 166, 348–354 (2007).

    Article  PubMed  Google Scholar 

  87. Button, K. S. et al. Power failure: why small sample size undermines the reliability of neuroscience. Nat. Rev. Neurosci. 14, 365–376 (2013).

    Article  CAS  PubMed  Google Scholar 

  88. Greenland, S. & Morgenstern, H. Confounding in health research. Annu. Rev. Public Health 22, 189–212 (2001).

    Article  CAS  PubMed  Google Scholar 

  89. Benner, J. S. et al. Long-term persistence in use of statin therapy in elderly patients. JAMA 288, 455–461 (2002).

    Article  PubMed  Google Scholar 

  90. Robins, J. M., Hernán, M. A. & Brumback, B. Marginal structural models and causal inference in epidemiology. Epidemiology 11, 550–560 (2000).

    Article  CAS  PubMed  Google Scholar 

  91. Hernán, M. A., Brumback, B. & Robins, J. M. Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men. Epidemiology 11, 561–570 (2000).

    Article  PubMed  Google Scholar 

  92. Robins, J. M. in Statistical Models in Epidemiology: The Environment and Clinical Trials (eds Berry, D. & Halloran, M. E.) 95–134 (Springer-Verlag, 1999).

    Google Scholar 

Download references

Acknowledgements

M.C.P. receives a grant from the National Institute on Aging (T32 AG027668). Funding was provided to M.C.P., J.W. and D.B. from the Alzheimer's Drug Discovery Foundation (ADDF). The ADDF catalyses and funds drug discovery and drug development for Alzheimer disease (AD) and related disorders. To learn more about the ADDF, visit the website at www.alzdiscovery.org. The funding agencies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. This work has not previously been presented in any form. However, the literature review and quality assessment were completed in parallel with work completed for the AlzRisk website (www.alzrisk.org), which attempts to catalogue epidemiological reports on risk factors for AD and to provide a continually updated, publically available assessment of the state of the literature. The AlzRisk database entry on statins, which is currently limited to studies reporting on AD as an end point, will be updated as new studies are published. We would like to thank John Jackson for his work in developing AlzRisk search strategies, which informed our search strategy, and his insight into the accuracy of electronic medical records in ascertaining dementia status.

Author information

Authors and Affiliations

  1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, 21205, MD, USA

    Melinda C. Power & A. Richey Sharrett

  2. Department of Internal Medicine, Rush Institute for Healthy Aging, 1653 West Congress Parkway, Chicago, 60612, IL, USA

    Jennifer Weuve

  3. Department of Psychiatry, Harvard Medical School and Massachusetts General Hospital, 55 Fruit Street, Boston, 02114, MA, USA

    Deborah Blacker

  4. Department of Neurology, Johns Hopkins School of Medicine, 733 North Broadway, Baltimore, 21205, MD, USA

    Rebecca F. Gottesman

Authors
  1. Melinda C. Power
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Jennifer Weuve
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. A. Richey Sharrett
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Deborah Blacker
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Rebecca F. Gottesman
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

M.C.P. conducted the literature search, determined study eligibility, extracted the data, conducted the quality assessment, and drafted the manuscript. All authors made substantial contributions to the analysis and interpretation of the data and critically revised the manuscript for important intellectual content. All authors gave final approval for publication.

Corresponding author

Correspondence to Rebecca F. Gottesman.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Box 1

Database search terms used for the literature search (DOCX 24 kb)

Supplementary Box 2

Details of data extraction from eligible articles (DOCX 22 kb)

Supplementary Box 3

Exploration of the potential magnitude of selection bias (DOCX 55 kb)

Supplementary Table 1

Summary of RCTs that reported on statins and cognitive outcomes according to the length of the follow-up period (DOCX 32 kb)

Supplementary Table 2

Summary of observational studies that reported on the association between baseline statin use and either cognitive change or incident dementia (DOCX 27 kb)

Supplementary Table 3

Summary of observational studies that reported on the association between time-updated statin use and incident dementia (DOCX 27 kb)

Supplementary Table 4

Summary of observational studies that considered participants' history of statin use during follow-up, and their cognitive outcomes (DOCX 29 kb)

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Power, M., Weuve, J., Sharrett, A. et al. Statins, cognition, and dementia—systematic review and methodological commentary. Nat Rev Neurol 11, 220–229 (2015). https://doi.org/10.1038/nrneurol.2015.35

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneurol.2015.35

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing
pFad - Phonifier reborn

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.

Note: This service is not intended for secure transactions such as banking, social media, email, or purchasing. Use at your own risk. We assume no liability whatsoever for broken pages.


Alternative Proxies:

Alternative Proxy

pFad Proxy

pFad v3 Proxy

pFad v4 Proxy