Abstract
We aimed to evaluate the association between statin use and cognitive function. Cognitive function was measured with the Ruff Figural Fluency Test (RFFT; worst score, 0; best score, 175 points) and the Visual Association Test (VAT; low performance, 0–10; high performance, 11–12 points) in an observational study that included 4,095 community-dwelling participants aged 35–82 years. Data on statin use were obtained from a computerized pharmacy database. Analysis were done for the total cohort and subsamples matched on cardiovascular risk (N = 1232) or propensity score for statin use (N = 3609). We found that a total of 904 participants (10%) used a statin. Statin users were older than non-users: mean age (SD) 61 (10) vs. 52 (11) years (p<0.001). The median duration of statin use was 3.8 (interquartile range, 1.6–4.5) years. Unadjusted, statin users had worse cognitive performance than non-users. The mean RFFT score (SD) in statin users and non-users was 58 (23) and 72 (26) points, respectively (p<0.001). VAT performance was high in 261 (29%) statin users and 1351 (43%) non-users (p<0.001). However, multiple regression analysis did not show a significant association of RFFT score with statin use (B, −0.82; 95%CI, −2.77 to 1.14; p = 0.41) nor with statin solubility, statin dose or duration of statin use. Statin users with high doses or long-term use had similar cognitive performance as non-users. This was found in persons with low as well as high cardiovascular risk, and in younger as well as older subjects. Also, the mean RFFT score per quintile of propensity score for statin use was comparable for statin users and non-users. Similar results were found for the VAT score as outcome measure. In conclusion, statin use was not associated with cognitive function. This was independent of statin dose or duration of statin use.
Highlights
Cardiovascular risk factors are associated with coronary heart disease and stroke and with cognitive dysfunction, due to shared atherosclerotic complications [1,2,3]
Statin use was not associated with cognitive function
The three subsamples from the final study population (Fig. 1) consisted of 1808 statin users and non-users matched on age, sex and educational level, 1232 statin users and non-users matched on cardiovascular risk, and 3609 of statin users and non-users who could be compared by quintile of propensity score for statin use
Summary
Cardiovascular risk factors are associated with coronary heart disease and stroke and with cognitive dysfunction, due to shared atherosclerotic complications [1,2,3]. Two randomized controlled trials (RCTs) have studied the effect of statin use on cognitive function and both failed to show a beneficial effect [7, 8]. One explanation could be the relatively short duration of these RCTs. Possibly, statins need a longer period to have a positive effect on cognitive function. Elderly with. years of continuous statin use had less cognitive decline than subjects who used statins less intensively [12]. In line with these data a recent meta-analysis found no short-term effects on cognitive function, whereas long-term use might be associated with a beneficial role in the prevention of dementia [17]. Confounding by indication can be an important limitation of observational studies as, generally, statin users have a different cardiovascular risk profile than non-users, and this type of bias needs to be addressed
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