Study Questions Statin, Memory Loss Connection

Statin and nonstatin use both associated with increased complaints of memory loss

Beginning treatment with a statin was associated with a nearly fourfold increased risk of developing acute memory loss within 30 days in a retrospective cohort study, but a similar increase in risk was seen in patients starting non-statin lipid-lowering drugs.

Compared with non-users, both statin and non-statin lipid-lowering drug (LLD) use was found to be associated with acute memory loss in the weeks following treatment initiation, but there was no difference in memory loss when statins and non-statins were compared with each other, researcher Brian L. Strom, MD, of Rutgers University in Newark, N.J., and colleagues wrote online June 8 in JAMA Internal Medicine.

The observation that all LLDs were associated with memory loss suggests that either all drugs used to lower lipid levels cause acute memory loss or that the observed memory loss in the study was due to detection bias, Strom said.

In a telephone interview with MedPage Today, Strom said it makes sense that patients on a new drug would be more likely to notice symptoms and attribute them to the drug, and they are also more likely to report such symptoms to their physician.

"Patients might report a memory loss to me that they would otherwise pay little attention to because I am seeing them more often and I ask them about it," he said.

Earlier Statin, Memory Studies Mixed

Several previous studies have shown acute memory loss associated with the use of statins, but others have not shown the association or have even shown improved memory in long-term statin users compared with non-users.

Strom noted that without the non-statin LLD control group in his study, the findings would have shown a strong association between statin initiation and short-term memory loss.

"In the absence of this control group, the finding would have been completely misleading," he said.

The study included data obtained between early 1987 through late 2013 from The Health Improvement Network (THIN), which is a comprehensive database of medical records from general practitioners in the U.K. Patients were excluded from the analysis if they had a diagnosis of Alzheimer's disease or dementia, if they had received medications used for dementia, or if they had other conditions affecting cognition, such as Parkinson's disease, Huntington's disease, or vascular dementia.

The analysis compared 482,543 statin users with 482,543 matched non-users of any lipid-lowering drug (control group 1) and with 26,484 users of non-statin LLDs, such as cholestyramine, colestipol hydrochloride, colesevelam, clofibrate, gemfibrozil, and niacin (control group 2).

A secondary case-crossover analysis was performed that included 68,028 patients with incident acute memory loss whose exposure to statins was evaluated during the period immediately before the outcome versus three earlier periods (31 to 60 days prior, 150 to 180 days prior, and 270 to 300 days prior).

Non-statin LLD Users Had 3.6-Fold Risk Increase

The analysis revealed that:

• When compared with matched non-users of any LLDs, there was a strong association between first exposure to statins and acute memory loss within 30 days immediately following exposure (fully adjusted odds ratio 4.40, 95% CI 3.01-6.41).
• The association was not seen in the comparison of statin versus non-statin LLDs (fully adjusted OR 1.03, 95% CI 0.63-1.66).
• The association was seen in the first 30 days following exposure in non-statin LLD users compared with matched non-user controls (adjusted OR 3.60, 95% CI 1.34-9.70).
• Both atorvastatin and simvastatin showed an increased OR within the first 30 days after exposure compared with non-users (adjusted OR 2.40, 95% CI 1.42-4.04 and 3.53, 95% CI 2.79 -4.48, respectively).
• The case-crossover analysis showed a weak negative association, which was not found to be clinically meaningful.

A potential study limitation cited by the researchers involved a substantial difference in baseline characteristics between users of statins and users of non-statin LLDs, and differences among users of the various statin drugs.

"Bias from confounding by indication is the most serious potential problem in this study, even though we attempted to control for indication variables and a large number of other underlying conditions," the researchers wrote.

The case-crossover analysis was conducted to address this issue because each patient served as his or her own control.

Statin, Memory Issue 'Tempest in Teapot'

The researchers also noted that potential confounding could exist for variables not recorded in the medical records database.

Strom said the study findings should reassure both patients and physicians who prescribe statins.

"This whole issue of short-term memory loss with statins is really a tempest in a teapot," he said. "Statins are very effective drugs, and people should not veer away from them for fear of a short-term memory effect, especially given the data suggesting that long-term statin use improves memory."

The research was funded by the National Institutes of Health.

Strom reported receiving research funding from AstraZeneca and Bristol-Myers Squibb and serving as a consultant to Abbott, AstraZeneca, Bayer Healthcare, Bristol-Myers Squibb, Novartis and Pfizer. A co-author reported receiving research funding from AstraZeneca and Bristol-Myers Squibb and serving as a consultant to AstraZeneca, Bayer Healthcare, Bristol-Myers Squibb, and Merck.