No convincing evidence of measurable verbal or nonverbal memory dysfunction due to statin
The Effect of High-Dose Atorvastatin on Neural Activity and Cognitive Function
Gepresenteerd tijdens ACC.17 door Beth Taylor
Mild central nervous system (CNS) complaints are the second most commonly reported adverse effect of statin drugs. In 2012 the FDA added the risk of adverse cognitive effects to the label of all statins. Study findings have, however, been inconclusive, possibly because observational studies are prone to prescription bias or because traditional cognitive tests yield small effect sizes.
This trial aimed to assess the effect of statins on cognition in a randomised clinical trial, using a battery of standard paper-based neuropsychological assessments and a self-reported cognitive failures questionnaire (CFQ). Moreover, neural activation with fMRI during two tasks was analysed (visual figural memory task and a verbal Sternberg working memory task).
Patients of 20 years and older were recruited from an ongoing RCT. The Statins On Skeletal Muscle Performance (STOMP) was designed to assess the incidence of muscle side-effects in 420 healthy, statin-naïve adults, who were treated with 80 mg atorvastatin or placebo daily for 6 months. Cognitive testing was performed after six months on treatment. The tests were repeated after participants ceased treatment for two months.
- Minimal effects of treatment were seen on neuropsychological test scores: in a test of auditory memory, scores for total and delayed recall improved with drug cessation in both groups. In the placebo group, performance on the Stroop colour-word score (measuring attention, reasoning and executive functioning) increased and the score for the 18-point clock test (evaluating mild cognitive impairement) scored decreased with drug cessation.
- No differences were seen in CFQ scores by total score, frequency of score or domain (memory, distractability, blunders and names).
- 42 Participants on placebo and 35 on atorvastatin were included in fMRI analysis. In the figural memory task, a group x time interaction was seen in bilateral paracentral lobule/precuneus during the encoding phase. Participants on atorvastatin had more blood oxygen level dependent (BOLD) response than participants on placebo while on treatment, but after treatment cessation their BOLD response was less. Neither group showed a significant change in BOLD response between scans.
- In the Sternberg Task, a group x time interaction was seen in the right putamen, extending into the right globus pallidus during the maintenance phase. Participants on atorvastatin showed less BOLD response during treatment, but more after treatment washout. The atorvastatin group showed a trend towards an increase in BOLD response between scans, which was not seen in the placebo group. No group x time effects were seen during the encoding phase or the retrieval phase.
- No significant differences were seen in neuropsychological tests evaluating visual memory, general cognitive function and neuronal impairment, manual dexterity or working memory.
This study showed few changes between treatment groups in standardised neuropsychological tests, which is congruent with large clinical trials.
Case reports of memory decrements with statin therapy continue to be published, and patients report cognitive side effects as a leading cause of statin intolerance. It is unclear to date whether this is due to a nocebo effect. Methodological issues (small effect sizes, learning/practice effects) may also play a role.
This study was the first to investigate the effects of statins on the CNS using fMRI. No convincing evidence of measurable verbal or nonverbal memory dysfunction due to statin medications was found. Most regional networks activated similarly by both groups. Patients on atorvastatin demonstrated small but significantly altered patterns of regional neural activation on vs. off statin, as compared to participants on placebo. The clinical implications of these findings are unclear and warrant additional clinical trials.
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