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#341 Forget about it? Statins and the risk of dementia


CLINICAL QUESTION
QUESTION CLINIQUE
Do statins negatively affect cognition, memory, or dementia?


BOTTOM LINE
RÉSULTAT FINAL
Randomized controlled trials (RCTs) and large, long-term observational studies suggest no association between statins and risk of dementia or worsening cognition scores.



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EVIDENCE
DONNÉES PROBANTES
  • Previous Tools for Practice (published in 2014) found no evidence that statins increase dementia risk or negatively affect cognition.1 Evidence presented below published since 2014.
  • Incidence of Dementia:
    • One systematic review2 of RCTs, simvastatin versus placebo.2 At 5 years:
      • Incidence of dementia (one RCT, 20,536 patients): 0.3% each group (no difference).
    • Three RCTs3-5 not in above systematic reviews (732-2,361 patients), statin versus placebo, followed 5-7 years, risk of dementia:
      • Largest RCT: No difference;4
      • Smaller RCTs suggest statins reduce risk.3,5 Example (732 patients), cognitive impairment incidence: 11% versus 19% (placebo), number need to treat=12.
    • Six systematic reviews6-11 of observational studies, statin versus no statin (13-46 observational studies, mean age 44-81 years), followed 1-25 years:
      • Examples from most reliable systematic review:6
        • All-cause dementia (16 studies): Relative risk reduction (RRR) 15%.
        • Alzheimer’s disease (14 studies): RRR 28%.
        • Vascular dementia (4 studies): No difference.
      • Other systematic reviews found similar.7-11
  • Cognition Scores:
    • Four systematic reviews of RCT, statin versus placebo in patients with/without baseline cognitive impairment:
      • No difference in Mini-Mental State Examination score,2,12-14 Telephone Interview Cognitive Status,2 Stroop Word,2 Activities of Daily Living score,12,14 Alzheimer’s Disease Assessment Scale (Cognitive),12-14 or Neuropsychiatric Inventory Scale.12,14
    • Two RCTs (described above):4-5 Found similar.
  • Adverse Events:
    • Two systematic reviews (2 studies each, 1045-26,340 patients), statins and placebo in patients with/without dementia: No difference.2,15
  • Limitations:
    • Most large RCTs evaluating statin cognitive effects are secondary analyses of larger cardiovascular trials.
    • Diagnosis of cognitive decline/dementia varied among trials.
    • Results of observational studies are less reliable due to biases (example, ‘healthy user effect’: Lower risk patients more likely to use statins).

CONTEXT
CONTEXTE
  • International guidelines vary: Statins have no effect16 or inconclusive effects17 on cognition.
  • An ongoing community based RCT: Evaluating effects of statins on aging, including dementia. Results expected in 2025.18


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Author(s)
Auteur(s)
  • Samantha S. Moe PharmD
  • Jennifer Young MD CCFP-EM

1. Gracias G, Garrison S, Allan GM. Can Fam Physician. 2014; 60(8):e391.

2. McGuinness B, Craig D, Bullock R, et al. Cochrane Database Syst Rev. 2016; 1:CD003160.

3. Zhang H, Cui Y, Zhao YX, et al. Hypertens Res. 2019; 42:717-29.

4. Bosch J, O’Donnell M, Swaminathan B, et al. Neurology. 2019; 92:e1435-e1446.

5. Hu WJ, Li Y, Zhao YX, et al. Front. Aging Neurosci. 2020; 12:1-13.

6. Chu CS, Tseng PT, Stubbs B, et al. Sci Rep. 2018; 8:5804:1-12.

7. Zhang XY, Wen JZ, Zhang ZQ. Medicine. 2018; 97:30(e11304):1-7.

8. Poly TN, Islam MM, Walther BA, et al. Neuroepidemiology. 2020; 54:214-226.

9. Olmastroni E, Molari G, De Beni N, et al. Eur J Prev Cardiol. 2022; 29:804-814.

10. Larsson SC, Markus HS. J Alzheimers Dis. 2018; 64:657-68.

11. Macedo AF, Taylor FC, Casas JP. BMC Medicine. 2014; 12:51.

12. Xuan K, Zhao TM, Qu GB, et al. J Neurol Sci Res. 2020; 41:1391-1404.

13. Ott BR, Daiello LA, Dahabreh IJ, et al. J Gen Intern Med. 2015; 30(3):348-58.

14. Liang T, Li R, Cheung O. Eur Neurol. 2015; 73:360-6.

15. Davis K, Bishara D, Perea G, et al. JAGS. 2020; 68:650-658.

16. Grundy SM, Stone NJ, Bailey AI, et al. Circulation. 2019; 139:e1082-e1143.

17. US Preventive Services Task Force. JAMA. 2022; 328(8):746-53.

18. Monash University. STAREE: Statins in Reducing Events in the Elderly. Available at: https://www.monash.edu/medicine/staree/home. Accessed February 10, 2023.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.