Reassurance that statins do not affect cognitive function?
The effects of statins on memory is a hot topic for the general public, so it is no surprise that an Australian study examining the rate of cognitive decline with statins was widely covered in the lay press. The authors concluded, “This study offers reassurance to consumers who hold concerns about harmful statin effects on memory and cognition.” I agree that the study offers reassurance, but I do not think it offers much reassurance. Why?
The study was a prospective, observational study of 1037 Australians aged 70 to 90 years. Prospective is always good, but observational is always an issue. Patients selected by their clinicians for statin treatment may have a better physical and cognitive prognosis than the non-treated group. For example, subjects who used statins continuously had higher baseline cognitive function than never users. It is reassuring that the rate of decline was similar between the continuous statin users and never users, but should the rate of decline be the same if the baselines were different? Maybe those smarter at baseline would have declined more rapidly, or less rapidly, without statins and the statin altered that. We just do not know.
The study was large, which is always good, but the 1037 subjects were divided into statin ever users (n = 642), statin never users (n = 395), continuous statin users (n = 444), and statin starters (n = 99), which can create some fairly small subgroups. So, although statins appeared to slow the rate of memory decline in those who started them during the study, we must remember that this is based on only 99 individuals, who may have been selected to receive statin therapy because of their good prognosis.
Furthermore, complete data are available for only 573 participants over the 6 years, and this reviewer is not totally clear on how missing values were addressed. The 464 participants with missing data were older, less educated, and more likely to be from a non–English speaking background. How such issues affect the results is unclear. The study also included MRI of the brain’s key memory areas, the hippocampus and parahippocampus, at baseline in 529 and after 2 years in 408. There were no differences in change in these areas between the statin and no statin groups, but what happened to over 20% of that study population?
The above issues are problems for this study, but no study is perfect, and some of the results are intriguing. Specifically, apolipoprotein E4 (apo E4) is a predictor of Alzheimer’s disease. Of the 395 statin never users, 72 (19.7%) had one allele for apo e4 whereas 614 statin ever users, 149 (24.2%), had an apo e4 allele. Those with apo e4 treated with statins had a remarkably slower rate of decline in a test of delayed recall. This begs confirmation to see if statins are an effective treatment for those with this Alzheimer’s risk factor.
We were among the first to raise the possibility that statins cause cognitive problems in rare individuals, something we documented with function MRI measurements.1 Our report was among those used by the FDA to insert a warning about possible decline into the statin package inserts.2 Overall, we think that statins reduce cognitive decline possibly by reducing vascular dementia produced by small embolic events.3 Clinically, however, I still see a rare patient with a convincing story of reversible cognitive impairment on statin therapy.
So, how will I use this study clinically? I will use it just as the authors suggested: as reassurance for patients and the public. I will tell them that a large, prospective, study using both cognitive testing and imaging of the brain memory centers did not show any adverse cognitive effects from statins. I will use it to encourage patients to take these lifesaving drugs. Sure, I have some reservations about the certainty of the results and a suspicion that an extremely rare patient may develop cognitive effects from statins. Statins are just too good to let anything scare patients away.
References
- Parker B, Polk D, Rabdiya V, et al. Changes in memory function and neuronal activation associated with atorvastatin therapy. Pharmacotherapy. 2010;30(6):625. https://accpjournals.onlinelibrary.wiley.com/doi/10.1592/phco.30.6.625
- Statin label changes. Med Lett Drugs Ther. 2012;54(1386):21. https://secure.medicalletter.org/article-share?a=1386a&p=tml&title=Statin%20Label%20Changes
- Thompson PD, Panza G, Zaleski A, Taylor B. Statin-associated side effects. J Am Coll Cardiol. 2016;67(20):2395–2410. https://www.sciencedirect.com/science/article/pii/S0735109716016922
Reproduced from:https://www.practiceupdate.com/content/no-association-between-statin-use-and-memory-cognition-or-brain-volume-in-the-elderly/92805/12/2/1
