In 2017, I wrote a post concluding that there was of the widely-utilized statin cholesterol-lowering drugs.
Despite this, a common concern of my patients when we discuss potentially utilizing statin drugs to reduce their long-term risk of heart attack and stroke is that the drug will rob them of their memory.
More studies have been published in this area, and they continue to show absolutely no evidence for adverse association between statins and cognition.
A recent found no beneficial or detrimental associations between statins and cognition in elderly cohorts with normal baseline cognition, impaired cognition, or with incident dementia.
Finally, and most recently, we have reassuring evidence from Australian researchers who meticulously studied over a thousand participants ages 70-90 years in the Sydney Memory and Ageing Study.
Over 6 years, the :
- No difference in the rate of decline in memory or global cognition between statin users and never users
- A blunted rate of memory decline with statin initiation during the observation period
- Attenuated decline in specific memory test performance in statin users with heart disease and apolipoprotein Eε4 carriage, in an exploratory analysis
- No difference in brain volume changes between statin users and never users
For those who see statins as part of a conspiracy, please note that there was absolutely no connection between the researchers and the statin pharmaceutical industry:
"This study was supported by the Australian Government's National Health and Medical Research Council (Dementia Research Grant 510124). Dr. Brodaty has served on the Nutricia Australia Advisory Board. Dr. Sachdev has served on the Australian Advisory Board of Biogen. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose."
My 2017 post was triggered by a call from a reporter who wanted to discuss the "cognitive side effects" of statins. It goes into a fair amount of detail about media and internet fear-mongering and how this contributes to the nocebo effect that makes it more likely patients will experience adverse side effects from medicine.
At the end, I discuss how we handle potential side effects in my practice.
I've copied it below as it remains highly relevant 2 years later.
Do Statins Cause Memory Loss? The Science, The Media, The Statin-Denialist Cult, and The Nocebo Effect
Because I regularly prescribe statin drugs to my patients to reduce their risk of heart attack and stroke, I am very concerned about any possible side effects from them, cognitive or otherwise. However, in treating hundreds of patients with statins, I have not observed a consistent significant effect on brain function.
When the FDA issued a statement in 2012 regarding rare postmarketing reports of ill-defined cognitive impairment associated with statin use, it came as quite a surprise to most cardiologists.
The FDA made a change in the patient information on all statin drugs that stated: "Memory loss and confusion have been reported with statin use. These reported events were generally not serious and went away once the drug was no longer being taken."
This FDA statement was surprising because prior observational and randomized controlled trials had suggested that patients who took statins were less likely to have cognitive dysfunction than those who didn't.
Early studies implied that statins might actually protect against Alzheimer's disease.
In fact, these signals triggered testing if statins could slow cognitive decline in patients with established Alzheimer's disease. One study used 80-mg atorvastatin versus placebo and a second used 40-mg simvastatin versus placebo; both showed no effect on the decline of cognitive function over 18 months.
More recently, multiple and have examined the data and concluded that there is no significant effect of statins on cognitive function. Importantly, these have been written by reputable physician-scientists with no financial ties to the pharmaceutical industry.
Data Show No Evidence of Causality Despite Case Reports
The FDA added the warning to statin patient information based on case reports. Occasional reports of patients developing memory loss on a statin do not prove that statins are a significant cause of cognitive dysfunction.
Case reports have to be viewed in the context of all the other scientific studies indicating no consistent evidence of negative effects of the statins. Case reports are suspect for several reasons:
First, patients receiving statins are at increased risk for memory loss because of associated risk factors for atherosclerosis and advancing age. A certain percentage of such patients are going to notice memory loss independent of any medications.
Second, the nocebo effect. If a patient taking a statin is told that the drug will cause a particular side effect, that patient will be more likely to notice and report that particular side effect.
A recent looked at reported side effects in patients taking atorvastatin versus placebo and found substantial evidence for the nocebo effect.
Analysis of the trial data revealed that when patients were unaware whether they were taking a statin or a placebo, the number of side effects reported was similar in those taking the statin and those taking placebo. However, if patients knew they were taking statins, reports of muscle-related side effects in particular increased dramatically, by up to 41%.
Third, a showed the rate of cognitive-related adverse events with statins is not significantly higher than for other non-statin cardiovascular medications (1.9 vs 1.6 per million prescriptions for losartan and 1.9 per million prescriptions for clopidogrel [Plavix]).
What Most Media Prefer: Controversy and Victims
I thought my experience and perspective on statins and cognitive function might be useful for a wider audience of patients to hear, so I agreed to be interviewed. After I expressed interest, the reporter responded:
"I would like to interview you and also a person who has experienced memory and/or thinking problems that they attribute to statin use."
I responded with "let me see what I can find," although I was concerned that this reporter was searching for a cardiologist to support attention-grabbing claims of severe side effects of statins rather than seeking a balanced, unbiased perspective from a knowledgeable and experienced cardiologist.
If I produced a "victim" of statin-related memory loss, this would boost ratings.
I then began racking my brain to come up with a patient who had clearly had statin-related memory loss or thinking problems. I asked my wonderful medical assistant, Jenny (who remembers details about patients that I don't), if she could recall any cases. Ultimately, we both came up without any patients for the interview. (Any patient of mine reading this with definite statin memory loss, please let me know and I will amend my post. However, I won't be posting anecdotes outside of my practice.)
I have had a few patients relate to me that they feel like their memory is not as good as it was and wonder if it could be from a medication they are on. Invariably, the patient has been influenced by one of the statin fear-mongering sites on the internet (or a friend/relative who has been influenced by such a site).
I wrote about one such site in response to a patient question a while back:
"The link appears to be a promotional piece for a book by Michael Cutler, MD. Cutler's website appears to engage in fear-mongering with respect to statins for the purpose of selling his books and promoting his 'integrative' practice. I would refer you to my post entitled Integrative medicine is another code word for pseudoscientific medicine and practitioners should be assiduously avoided."
"The piece starts with describing the case of Duane Graveline, a very troubled man who spent the latter part of his life attempting to scare patients from taking statins." .
"You can judge for yourself if you want to base decisions on his recommendations."
"There is no scientific evidence to suggest statins cause dementia."
An Internet-Driven Cult With Deadly Consequences
Steve Nissen, MD, recently wrote an that accuses statin deniers of being an "internet-driven cult with deadly consequences." has done extremely important research helping us better understand atherosclerosis and is known for being a patient advocate -- calling out drug companies when they are promoting unsafe drugs.
I have immense respect for his honesty, lack of bias, and his courage to be outspoken. He writes:
"Statins have developed a bad reputation with the public, a phenomenon driven largely by proliferation on the Internet of bizarre and unscientific but seemingly persuasive criticism of these drugs. Typing the term statin benefits into a popular Internet search engine yields 655 000 results. A similar search using the term statin risks yields 3 530 000 results. One of the highest-ranking search results links to an article titled 'The Grave Dangers of Statin Drugs -- and the Surprising Benefits of Cholesterol.' We are losing the battle for the hearts and minds of our patients to Web sites developed by people with little or no scientific expertise, who often pedal 'natural' or 'drug-free' remedies for elevated cholesterol levels. These sites rely heavily on 2 arguments: statin denial, the proposition that cholesterol is not related to heart disease, and statin fear, the notion that lowering serum cholesterol levels will cause serious adverse effects, such as muscle or hepatic toxicity -- or even worse, dementia."
He goes on to point out that this misinformation is contributing to a low rate of compliance with taking statins. Observational studies suggest that noncompliance with statins significantly raises the risk of death from heart attack.
The reasons for patient noncompliance, Nissen goes on to say, can be related to the promotion of totally unproven supplements and fad diets as somehow safer and more effective than statin therapy:
"The widespread advocacy of unproven alternative cholesterol-lowering therapies traces its origins to the passage of the Dietary Supplement Health and Education Act of 1994 (DSHEA). Incredibly, this law places the responsibility for ensuring the truthfulness of dietary supplement advertising with the Federal Trade Commission, not the U.S. Food and Drug Administration. The bill's principal sponsors were congressional representatives from states where many of the companies selling supplements are headquartered. Nearly 2 decades after the DSHEA was passed, the array of worthless or harmful dietary supplements on the market is staggering, amounting to more than $30 billion in yearly sales. Manufacturers of these products commonly imply benefits that have never been confirmed in formal clinical studies."
Dealing With Statin Side Effects In My Practice
When patients tell me they believe they are having a side effect from the statin they are taking (and this applies to any medication they believe is causing them side effects), I take their concerns very seriously. After 30 years of practice, I've concluded that in any individual patient, it is possible for any drug to cause side effects. And, chances are that if we don't address the side effects, the patient won't take the medication.
If the side effect is significant, I will generally tell the patient to stop the statin and report to me how they feel after 2 to 4 weeks.
If there is no improvement, I have the patient resume the medication and we generally reach a consensus that the side effect was not due to the medication.
If there is a significant improvement, I accept the possibility that the side effect could be from the drug. This doesn't prove it, because it is entirely possible that the side effect resolved for other reasons coincidentally with stopping the statin. Muscle and joint aches are extremely common and they often randomly come and go.
At this point, I will generally recommend a trial at low dose of another statin (typically rosuvastatin or pitavastatin [Livalo]). If the patient was experiencing muscle aches and they return, we are most likely dealing with a patient with statin-related myalgia. However, most patients are able to tolerate low dose and less frequent administration of rosuvastatin or pitavastatin.
For all other symptoms, it is extremely unusual to see a return on rechallenge with statin and so we continue statin long-term therapy.
Today, a patient told me he thought the rosuvastatin we started 4 weeks ago was causing him to have more diarrhea. I informed him that there is no evidence that rosuvastatin causes diarrhea more often than a placebo and had no reason based on its chemistry to suspect it would. (Although I'm sure there is a forum somewhere on the internet where patients have reported this.) Fortunately, he accepted my expert opinion and will continue taking the drug.
If the symptoms persist and the patient continues to believe it is due to the statin, we will go through the process I described above. And, since every patient is unique, it is possible that my patient is having a unique or idiosyncratic reaction to the statin that only occurs in one out of a million patients and thus is impossible to determine causality.
Because statins are our most effective and best tolerated weapon in the war against our biggest killer, it behooves both patients and physicians to have a high threshold for stopping them altogether. Having such a high threshold means filtering out the noise from attention-seeking media and the internet-driven denialist cult, thus minimizing the nocebo effect.
is a private practice noninvasive cardiologist and medical director of echocardiography at St. Luke's Hospital in St. Louis. He blogs on nutrition, cardiac testing, quackery, and other things worthy of skepticism at , where a version of this post first appeared.