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Statins and cognitive function

Clinical bottom line

If there is any protective effect of statins on cognitive impairment, it is based on weak observational evidence.


Impairment of cognitive function, or dementia, is common in older people, with 10% of those aged 65 or more being affected. It is a heterogeneous condition with mixed causes, many of which involve vascular changes in the brain, and there is evidence for involvement of lipids in these changes. The mechanisms are poorly understood.

A review [1] found seven observational studies investigating the relationship between cognitive function and dementia. There were three case control, three cohort, and one observational study: five presented data on treatment with any lipid-lowering agent, and all seven on treatment with statins. Cognitive impairment was defined as "a diagnosis of Alzheimer's disease, dementia, or cognitive dysfunction, using each study's own definitions".

Results

All but one study (the observational study) adjusted for potential confounders and risk factors for dementia. There was a significant association between the use of a statin and reduced risk of cognitive impairment, compared to no use of any lipid lowering drug. The association with use of any lipid lowering drug compared to no use was weaker and not significant. The summary outcomes are presented in Table 1.

Table 1: Association between use of lipid lowering drugs and cognitive impairment

 
Odds ratio for cognitive impairment
95% CI
Any LLD: users vs non users
0.62
0.28-1.38
Statin users vs non users of any LLD
0.43
0.31-0.62
LLD = lipid lowering drug

Comment

The authors conclude that use of statins, and possibly other lipid lowering drugs, seems to reduce the risk of cognitive impairment, but stress the need for randomised controlled trials to confirm this and investigate questions about dosage, duration, and the effects in different types of dementia. They suggest that the benefit observed with statins compared to other lipid lowering drugs may indicate a mechanism that is independent of cholesterol lowering, such as an antioxidant or anti-inflammatory effect. This is supported by the finding in one study that there was no significant difference in risk for groups with hyperlipidemia and either no drug or non statin lipid lowering drug treatment.

We should remember that these observational studies do not establish a causal link, although most made adjustments for a variety of confounding variables, and one investigated indication bias by adjusting for other markers for health, without affecting the result.

Bandolier 48 reviewed a study that showed how different ways of diagnosing dementia produce wildly differing results [2]. These observational studies use a range of diagnostic systems that could result in at least four-fold differences in estimates of prevalence. Knowing this we should be even more careful about these observational results.

References

  1. M Etminan et al. The role of lipid-lowering drugs in cognitive function: a meta-analysis of observational studies. Pharmacotherapy 2003 23: 726-730 [www.medscape.com/viewarticle/456866].
  2. T Erikinjuntti et al. The effect of different diagnostic criteria on the prevalence of dementia. New England Journal of Medicine 1997 337: 1667-74.
  3. J Shepherd et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002 360: 1623-1630.
  4. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002 360: 7-22.