A study involving nearly half a million statin users and the same number of nonusers failed to determine whether statin drugs harm memory.
Although the study, published online June 8 in JAMA Internal Medicine, showed that both statin and nonstatin lipid-lowering drugs (LLDs) were strongly associated with acute memory loss within 30 days of LLD exposure, the authors note those results could show that people treated with LLDs simply see their physicians more, so their physicians are more likely to detect memory loss.
The retrospective cohort study, conducted by Brian L. Strom, MD, MPH, chancellor, Rutgers Biomedical and Health Sciences, and executive vice president for health affairs at Rutgers University, Newark, New Jersey, and colleagues, relied on data collected in The Health Improvement Network (THIN) database between 1987 and 2013. THIN data are collected during routine practice by general practitioners in the United Kingdom.
The researchers compared 482,543 new statin users with individuals in two control groups: one of 482,543 matched individuals not using any LLDs and a second control group of 26,484 users of nonstatin LLDs. The groups were matched by sex, age group, and enrollment duration. In addition, a case-crossover study of 68,028 patients with acute memory loss examined statin exposure at various periods before the memory loss incident: within 30 days before the incident, between 31 and 60 days before the incident, between 150 and 180 days before the incident, and between 270 and 300 days before the incident. The investigators excluded patients with a history of cognitive issues, such as Alzheimer’s and dementia, as well as those with other issues involving the brain, including tumors, brain infections, and Down syndrome.
Researchers found a “strong association” between first exposure to statins and acute memory loss within 30 days in a comparison between statin users and nonusers (adjusted odds ratio [AOR], 4.40; 95% confidence interval [CI], 3.01 - 6.41). Further, the data also showed an association between the use of nonstatin LLDs and memory loss when compared with non-LLD users (AOR, 3.60; 95% CI, 1.34 - 9.70) in the first 30 days.
What are statin side effects?
Muscle pain and damage
The most common statin side effect is muscle pain. You may feel this pain as a soreness, tiredness or weakness in your muscles. The pain can be a mild discomfort, or it can be severe enough to make your daily activities difficult. For example, you might find climbing stairs or walking to be uncomfortable or tiring.
Very rarely, statins can cause life-threatening muscle damage called rhabdomyolysis (rab-doe-mi-OL-ih-sis). Rhabdomyolysis can cause severe muscle pain, liver damage, kidney failure and death. Rhabdomyolysis can occur when you take statins in combination with certain drugs or if you take a high dose of statins.
Occasionally, statin use could cause your liver to increase its production of enzymes that help you digest food, drinks and medications. If the increase is only mild, you can continue to take the drug. Rarely, if the increase is severe, you may need to stop taking the drug. Your doctor might suggest a different statin. Certain other cholesterol-lowering drugs, such as gemfibrozil (Lopid) and niacin (Niacor, Niaspan), slightly increase the risk of liver problems in people who take statins.
Although liver problems are rare, your doctor will likely order a liver enzyme test before or shortly after you begin to take a statin. You shouldn’t need any additional liver enzyme tests unless you begin to have signs or symptoms of trouble with your liver. Contact your doctor immediately if you have unusual fatigue or weakness, loss of appetite, pain in your upper abdomen, dark-colored urine, or yellowing of your skin or eyes.
Some people taking a statin may develop nausea, gas, diarrhea or constipation after taking a statin. These side effects are rare. Most people who have these side effects already have other problems with their digestive system. Taking your statin medication in the evening with a meal can reduce digestive side effects.
Rash or flushing
You could develop a rash or flushing after you start taking a statin. If you take a statin and niacin, either in a combination pill such as Simcor or as two separate medications, you’re more likely to have this side effect. Taking aspirin before taking your statin medication may help, but talk to your doctor first.
Increased blood sugar or type 2 diabetes
It’s possible your blood sugar (blood glucose) level may increase when you take a statin, which may lead to developing type 2 diabetes. The risk is small but important enough that the Food and Drug Administration (FDA) has issued a warning on statin labels regarding blood glucose levels and diabetes. Talk to your doctor if you have concerns.
Neurological side effects
The FDA warns on statin labels that some people have developed memory loss or confusion while taking statins. These side effects reverse once you stop taking the medication. Talk to your doctor if you experience memory loss or confusion. There has also been evidence that statins may help with brain function - in patients with dementia or Alzheimer’s, for example. This is still being studied. Don’t stop taking your statin medication before talking to your doctor.
However, when statin LLD users were compared with nonstatin LLD users, there was no association (AOR, 1.03; 95% CI, 0.63 - 1.66). The odds ratios were adjusted for confounders such as diabetes mellitus, hypercholesterolemia, cardiovascular disease, hypertension, stroke, antihypertensive drugs, alcohol abuse, Cushing syndrome, vitamin B12 deficiency, and several other health indicators.
Donna K. Arnett, PhD, MSPH, a spokesperson for the American Heart Association, told Medscape Medical News in an email that the study “suggests there is a modest association between statins and other lipid-lowering drugs and cognitive decline.” However, she and the authors note the possibility of confounding by indication because patients receiving LLDs had more medical problems that could be associated with memory loss than patients receiving non-LLDs.
Patients who were using non-statin cholesterol drugs reported the same short-term memory incidents as those using statins. This means, researchers said, that either all cholesterol-lowering drugs cause short-term memory loss, which is unlikely because the drugs have completely different structures, or these incidents blamed on a drug are the fault of “detection bias.”
“When patients are put on statins or any new drug, they’re seen more often by their doctor, or they themselves are paying attention to whether anything is wrong,” said Brian L. Strom, chancellor of Rutgers Biomedical and Health Sciences, in a press release. “So if they have a memory problem, they’re going to notice it. Even if it has nothing to do with the drug, they’re going to blame it on the drug.”
Further, there was the possibility of detection bias, she noted: “That the LLD cognitive decline was observed in both statins and nonstatin LLDs, it is more plausible that the drugs themselves reflect more frequent interaction with their physicians, which may result in a greater chance for detecting memory loss, rather than the drugs themselves causing the memory loss,” Dr Arnett said. She is past president of the American Heart Association and a professor and chair of the Department of Epidemiology, University of Alabama at Birmingham.
Past studies on the effect of statins on memory loss have been contradictory, with some showing an association between long-term statin use and improved memory and others showing no effect on memory. The authors of the current study draw no conclusions that end this uncertainty.
“Although we observed a large OR for acute memory loss in the 30-day period immediately following the start of statin use compared with no statin use as did previous studies, subsequent analyses showed an elevated OR for nonstatin LLDs as well,” the authors write. “This finding suggests that either all LLDs cause acute memory loss or, perhaps more likely, that the association is the result of a detection bias,” they conclude.
Previous studies had reported a possible connection between statins and memory loss, but those studies compared statin users to non-statin users. In his study, Strom included another group for comparison: people prescribed cholesterol-lowering drugs that were not statins. Among a large group of 482,543 statin users, 26,484 users of non-statin cholesterol-lowering drugs and 482,543 controls who weren’t on any drugs, Strom and his team found that both cholesterol-lowering drug groups showed short-term memory problems in the first 30 days after they started taking their medications compared to the controls. For statin users, the increased odds of memory lapses was four-fold, and for the other drug group, nearly the same, at 3.6-fold.
Because both groups taking drugs showed similar memory effects, Strom says that it’s unlikely that statins are uniquely to blame for the short-term cognitive issues. And because statins and the other cholesterol-lowering drugs work in vastly different ways, it’s also unlikely that the effect can be blamed on the drugs themselves. Strom proposes that the groups’ short-term memory issues, which were recorded by doctors in the patients’ medical records, is more likely the result of these patients simply being more aware of and sensitive to any changes in their functions after starting a new medication. In other words, people may have been having memory issues before they started their medications, and the problems might have occurred if they had not started taking them, but the symptoms became more noticeable because the users were more attuned to changes after filling their new prescription. The control group might have been experiencing similar memory issues but didn’t report them to their doctors; therefore, the issues might not have been recorded. “People on new medicines are more likely to notice a problem, more likely to blame problems on the drug and more likely to go back to the doctor and report these problems,” Strom says.
Dr Arnett has disclosed no relevant financial relationships. Dr Strom reports the receipt of research funding from AstraZeneca and Bristol-Myers Squib and serving as a consultant to Abbott, AstraZeneca, Bayer Healthcare LLC, Bristol-Myers Squibb, Novartis, and Pfizer. One coauthor reports receiving research funding from AstraZeneca and Bristol-Myers Squib and educational funds from Pfizer. He also acts as a consultant for AstraZeneca, Bayer Healthcare LLC, Bristol-Myers Squibb, and Merck.
JAMA Intern Med. Published online June 8, 2015. Abstract