The use of statin therapy in adults 65 years old or older may not be associated with incident dementia, mild cognitive impairment (MCI) or decline in individual cognition domains, according to a study published June 21 in the Journal of the American College of Cardiology.

Zhen Zhou, PhD, et al., analyzed data from the ASPREE trial – a large prospective, randomized placebo-controlled trial of daily low-dose aspirin, which included 19,114 participants 65 years old or older with no prior cardiovascular disease event, dementia or major physical disability, between 2010 and 2014 from Australia and the U.S. The researchers excluded participants with missing values for cognitive test scores and/or covariates at baseline, resulting in 18,846 participants. They were grouped by their baseline statin use versus non-statin use, with 5,898 (31.3%) of participants taking statins.

After a median of 4.7 years of follow-up, researchers found 566 incident cases of dementia (including probable Alzheimer's disease and mixed presentations). Compared with no statin use, statin use was not associated with risk of all-cause dementia, probable Alzheimer's disease or mixed presentations of dementia. There were 380 incident cases of MCI found (including MCI consistent with Alzheimer's disease and MCI-other). Compared to no statin use, statin use was not associated with risk of MCI, MCI consistent with Alzheimer's disease or other MCI. There was no statistically significant difference in the change of composite cognition and any individual cognitive domains between statin users versus non-statin users. Also, no significant differences were found in any of the outcomes of interest between users of hydrophilic and lipophilic statins. However, researchers did find interaction effects between baseline cognitive ability and statin therapy for all dementia outcomes.

"The present study adds to previous research by suggesting that statin use at baseline was not associated with subsequent dementia incidence and long-term cognitive decline in older adults," concludes Zhou.

However, the researchers note that their study has several limitations, including observational study bias. Further, they add that the study must be interpreted with caution and will require confirmation by randomized clinical trials designed to explore the neurocognitive effects of statins in older populations.

In an accompanying editorial comment, Christie M. Ballantyne, MD, FACC, and Vijay Nambi, MBBS, FACC, said "Overall, the analysis was well done, and its main strengths are a large cohort with a battery of standardized tests that allowed the investigators to track both cognition and incidence of dementia and its subtypes over time," they said. "Lingering questions such as the one raised by this analysis regarding potential adverse effects of statins in individuals with mildly impaired cognition can only be answered in randomized controlled trials in the appropriate age group and population and with appropriate testing and adequate follow-up. In the meantime, practicing clinicians can have confidence and share with their patients that short-term lipid lowering therapy in older individuals, including with statins, is unlikely to have a major impact on cognition."

Clinical Topics: Dyslipidemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Sleep Apnea

Keywords: Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiovascular Diseases, Alzheimer Disease, Cognition, Cognition Disorders, Cardiovascular System, Aspirin, Neuropsychological Tests, Lipids

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