Effect of Statins on Memory Loss Remains Uncertain

Jenni Laidman

June 08, 2015

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.

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.

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.

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

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