In 2017 I wrote a post entitled “Do Statins Cause Memory Loss? The Science, The Media, The Statin-Denialist Cult, and The Nocebo Effect” which concluded that there was no scientific evidence for cognitive side effects 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 summative review 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 aged 70-90 years in the Sydney Memory and Ageing Study.
Over 6 years the study found
-no difference in the rate of decline in memory or global cognition between statin users and never users.
-Statin initiation during the observation period was associated with blunting the rate of memory decline.
-Exploratory analyses found statin use was associated with attenuated decline in specific memory test performance in participants with heart disease and apolipoprotein Eε4 carriage.
-There was 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 which 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.
Since 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 U.S. Food and Drug Administration (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 which 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 two studies 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 40 mg simvastatin versus placebo and both showed no effect on the decline of cognitive function over 18 months.
More recently, multiple reviews and meta-analyses 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 study in The Lancet 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 per cent.
Third, a review of the FDA post-marketing surveillance data showed the rate of memory loss with statins is not significantly higher than for other non-statin cardiovascular medications (1.9 per million prescriptions for statins , 1.6 per million prescriptions for losartan) and clopidogrel (1.9 per million prescriptions for clopidogrel.)
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.
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 “functional medicine is fake medicine”. 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 vey troubled man who spent the latter part of his life attempting to scare patients from taking statins. Here is his NY Times obituary.
You can judge for yourself if you want to base decisions on his recommendations.There is no scientific evidence to suggest statins cause dementia.
“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 en- gine 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 de- veloped 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 Administra-tion. 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 a patient tells 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 two to four 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 livalo.) If the patient was experiencing muscle aches and they return we are most likely dealing with a patient with statin related myalgias. However, most patients are able to tolerate low dose and less frequent administration of rosuvastatin or Livalo.
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 continue 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.
Since 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 denials cult thus minimizing the nocebo effect
Antinocebonically Yours
-ACP
14 thoughts on “Statins And Memory Loss: The Latest Findings”
Interesting. So the nocebo effect come into account when you anticipate an affect. Odd because when I started a statin I had a positive outlook. I did not know what the side effects were nor did I know there was so much chatter online. Still the same I started experiencing severe muscle pain. Come to find out this is a common side effect. I believe your article over inflates your premise that statins are a wonder drug and incorrectly states that the side effects are rare or “all in a patients head”.
David,
I have no doubt there are many individuals who have experienced very real muscle pain while taking a statin drug who were not anticipating this side effect. I have dozens of patients who fit into that category. I have never told a single one the muscle pain was “all in their head”, that phrase is not in my patient discussion vocabulary.
A very fascinating study (the SAMSON study) was published as a letter in the NEJM recently.(https://www.nejm.org/doi/full/10.1056/NEJMc2031173)
Later published as a full paper, it showed that 90% of symptoms experienced on a statin where also experienced when the individual was taking a placebo.
The purpose of this study was to assess daily symptom scores on statin, placebo, and no treatment in participants who had abandoned statins.
Methods
Participants received 12 1-month medication bottles, 4 containing atorvastatin 20 mg, 4 placebo, and 4 empty. We measured daily symptom intensity for each using an app (scale 1-100). We also measured the “nocebo” ratio: the ratio of symptoms induced by taking statin that was also induced by taking placebo.
Results
A total of 60 participants were randomized and 49 completed the 12-month protocol. Mean symptom score was 8.0 (95% CI: 4.7-11.3) in no-tablet months. It was higher in statin months (16.3; 95% CI: 13.0-19.6; P < 0.001), but also in placebo months (15.4; 95% CI: 12.1-18.7; P < 0.001), with no difference between the 2 (P = 0.388). The corresponding nocebo ratio was 0.90. In the individual-patient daily data, neither symptom intensity on starting (OR: 1.02; 95% CI: 0.98-1.06; P = 0.28) nor extent of symptom relief on stopping (OR: 1.01; 95% CI: 0.98-1.05; P = 0.48) distinguished between statin and placebo. Stopping was no more frequent for statin than placebo (P = 0.173), and subsequent symptom relief was similar between statin and placebo. At 6 months after the trial, 30 of 60 (50%) participants were back taking statins.
Conclusions
The majority of symptoms caused by statin tablets were nocebo. Clinicians should not interpret symptom intensity or timing of symptom onset or offset (on starting or stopping statin tablets) as indicating pharmacological causation, because the pattern is identical for placebo. (Self-Assessment Method for Statin Side-effects Or Nocebo [SAMSON]; NCT02668016)
Whatever is causing the side effects in my patients on statins we work together to find an effective and well-tolerated medical regimen that reduces their risk of heart attack and stroke.
Last week I saw a patient who has experienced back pain so terrible that she couldn’t get out of bed after taking statin medications with previous doctors. We tried her on Repatha, an injectable that works in a totally different way than statins and she experienced the same symptoms. Most recently i trialed Zetia for her (a drug which lowers cholesterol by reducing intestinal aborption) and within 3-4 days she says her back pain became unbearable.
I don’t discount her symptoms and we continue to find ways to prevent her from having another heart attack.
Dr P
https://www.sourcewatch.org/index.php/Black_Dog_Institute
One of the researchers seemed to not give full disclosure of his work for Pfizer and Lilly.
He also made a cautionary statement on the findings.
Dr. Sachdev cautions, however, that because the study was observational and not a clinical trial, the findings are not conclusive.
Dear TSC,
I am skeptical regarding the benefit of statins in low risk individual despite my physician quoting stats that I should take it to reduce my risk further. I am not focused on mental side-effects but on the diabetes risk vs benefit and I am curious about your opinion of the presentation given at The Number Needed to Treat website (https://www.thennt.com/nnt/statins-persons-low-risk-cardiovascular-disease/). Low risk to me is no DM, HPTN, Prev MI, FHx of MI, or elevated triglycerides. My current numbers are Chol 172, Tri 77, HDL 51, LDLcalc 106 (and btw very low inflammatory markers). The NNT numbers say no fatal MI’s prevented; 1 in 217 avoided a nonfatal heart attack and 1 in 313 avoided a nonfatal stroke. I can’t bring myself to take a statin nor can I recommend others take it in similar circumstances.
Your colleague in skepticism,
Dan
Benefits of statins are low for truly low risk individuals. I agree. If on the fence about whether to take or not as I’ve written about on this site a fair amount it is a good idea to get more information on your true risk. Coronary artery calcium score, carotid IMT in the young with zero CAC, Lipoprotein (a) and apo (B) are useful for more precise risk stratification.
Since statins are known to reduce inflammation and inflammation is one of the major factors contributing to atherosclerosis over all and in the brain, I doubt that statins cause memory loss. Extensive well done studies have shown that reduction of LDL results in statistically lower CVD events and deaths and this reduction increases the longer a person has taken a statin. So the bottom line is that if you are diagnosed with CVD disease and have LDL > 100 mg/dl, statins will lower morbidity and mortality.
The cascade of pro-inflammatory cytokines is a response to vascular trauma, not the cause of it. You must look farther upstream for actual causes. Inflammation is the body’s first response in the healing process. All that logically follows a premise of inflammation causality needs to be reevaluated.
Interestingly, calcification is probably the last phase of healing – particularly of chronic injury. Statins increase vascular calcification. “Hardening of the arteries”. Now there’s food for thought.
Thank you for this amazing article. Truth be told, although I have been taking a statin for many years, the reassuring data from the studies sited isn’t what I appreciate the most. I worked as a clinical microbiologist and IC practitioner for 35+years. My mentor and co-worker was and still is a brilliant Ph.D Clinical microbiologist and researcher. ( I’m retired, he’s not) Together we co-authored close to a dozen articles in peer reviewed journals. ( Please note, he has published and presented literally hundreds of case studies and primary research in the US and internationally.) So, what’s my point? Working along side him fostered in me an overwhelming sense of skepticism ! It annoys the hell out of people who know me. And I’m fine with that. Probably why I look forward to reading your posts . Please keep up the fight to to bring unbiased information to those of us who still prefer to get our knowledge from double blind , peer reviewed sources rather than from Jenny McCarthy.
Thank you !
Sam,
I’m pleased as punch that I my skeptical articles are well received by those filled with skepticism!
I am so pleased to have stumbled on your site. I have been taking statins unwillingly for more than 20 years. on again off again before my triple bypass 13 years ago.
I have fell for the misinformation peddled by the likes of spacedoc,McKendrick and Sinatra and co for years. As you could imagine this has often caused me much confusion and anxiety.
This is the first time I have encountered the term nocebo. An apt term for where I am at. No more doubts ?
Is it true that the average patient would need to take statins for 5 years in order to see life expectancy increased by 5 days? (That’s a talking point in the anti-statin circles but I have not researched it in depth) – figure you might know off the top of your head. Thx, Mike
Mike,
I have seen an article that presents the information that way. This is in the setting of primary prevention-those that haven’t yet had a heart attack or sudden death. Of course, if you have suffered a stroke or heart attack but not died you may wish you had. These data on the “average patient” are ones which utilize standard risk factors to determine who is eligible for treatment, thus many with zero calcium scores are treated who won’t benefit and many with very advanced calcium scores are not treated.
Mike,
I believe this primarily applies to randomized trials. There is some filtering out of those individuals who can’t tolerate the study medication.
However, this new study is not a randomized trial.
Any chance “lead-in-periods” which exclude those most likely to experience a side effects from the study population might skew the ‘no-side-effect’ conclusions in studies?