Tools for Practice


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


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

BOTTOM LINE
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
  • 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
  • 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):

  • Jennifer Young MD CCFP-EM
  • Samantha S. Moe PharmD

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.