Statin Use Has No Negative Impact on Neurocognitive Health, According to New Analysis

Zhen Zhou, PhD

Analysis of data from the ASPREE study demonstrates statin use was not associated with increased prevalence of dementia or accelerated cognitive decline in older patients.

The subject of debate across specialties based on observational data, the new 18,000-patient analysis adds further evidence for the current knowledge base related to the effects of statin therapy on cognitive domains of older patients.

"With statins being increasingly prescribed to older adults, their potential long-term effects on cognitive decline and dementia risk have attracted growing interest," said lead investigator Zhen Zhou, PhD, Menzies Institute for Medical Research at the University of Tasmania in Australia, in a statement. "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."

To further explore the potential neurocognitive effects of statin use, Zhou and colleagues designed the current study as an analysis of data from within the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which was a randomized placebo-controlled trial of daily aspirin in 19,114 older adults with no history of cardiovascular disease, dementia or physical disability. After exclusion of those with missing information, a cohort of 18,846 patients with a median follow-up of 4.7 years was identified for inclusion in the current analysis.

Using data from ASPREE, which required patients to have a score of 78 or more on the Modified Mini-Mental State Examination (3MS) at enrollment, investigators planned to compare incidence of dementia and its subclassifications, mild cognitive impairment (MCI) and its subclassifications, and changes in domain-specific cognition based on statin use. For the purpose of analysis, investigators planned to evaluate potential associations using Cox proportional hazards models with cognitive change using linear mixed-effects models, adjusting for potential confounders. Investigators also planned to assess the impact of statin lipophilicity on potential associations.

The study cohort had a mean age of 74.0 (IQR, 71.6-77.7) years, 56.4% were women, and 91.3% identified as non-Hispanic White. Overall, 12,948 (68.7%) of patients were not using statins at baseline. In comparison, statin users were more likely to be female, have a lower average education level, take more medications at baseline, and to have a higher prevalence of obesity, CKD, diabetes, and hypertension.

A total of 566 incident cases of dementia and 380 incident cases of MCI were identified over 85,557 person-years of follow-up. Compared with no statin use, use of statins was not associated with risk for all-cause dementia (HR, 1.16; 95% CI, 0.97-1.40; P=.11), probable Alzheimer’s dementia (HR, 1.33; 95% CI, 1.00-1.77; P=.05), or mixed presentations of dementia (HR, 1.06; 95% CI, 0.82-1.35; P=.67). Similarly, statin use was not associated with increased risk for MCI (HR, 0.97; 95% CI, 0.77-1.22; P=.81), MCI consistent with Alzheimer’s dementia (HR, 1.44; 95% CI, 0.90-2.29; P=.13), or other MCI (HR, 0.86; 95% CI, 0.66-1.12; P=.26) when compared with no statin use.

When detailing findings for assessments of cognitive function over time, investigators noted statin users had significantly lower scores on global cognition, episode memory, and composite cognition when compared to nonusers. Results of these assessments indicated there were no statistically significant difference in change of composite cognitive and any cognitive domains between statin users and nonusers (P>.01 for all). Investigators also highlighted no significant differences were observed for any of the outcomes of interest based on use of hydrophilic or lipophilic statins.

Further analysis suggested baseline neurocognitive function was an effect modifier for the associations of statins with dementia (P for interaction <.001) and memory change (P for interaction=.02).

In an accompanying editorial, Christie Ballantyne, MD, Professor at Baylor College of Medicine, commended investigators for their study and findings but underlined the questions posed need proper assessment in randomized clinical trials.

"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,” wrote Ballantyne.

This study, “Effect of Statin Therapy on Cognitive Decline and Incident Dementia in Older Adults,” was published in the Journal of the American College of Cardiology.