Do cholesterol‐lowering agents affect brain activity? A comparison of simvastatin, pravastatin, and placebo in healthy volunteers.

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Abstract
1. The effects of simvastatin and pravastatin on measures of central nervous system activity were investigated in a double‐blind, placebo‐ controlled, randomised crossover study. 2. Twenty‐five healthy volunteers sequentially took 40 mg day‐1 simvastatin, 40 mg day‐1 pravastatin or placebo for 4 weeks, separated by a 4‐6 week washout phase. 3. CNS measures included EEG evoked potentials, power spectral analysis, Leeds Sleep Questionnaire, Hospital Anxiety Depression (HAD) Scale, and Digit Symbol Substitution Test (DSST); biochemical measures included plasma cholesterol, liver enzymes (gamma‐GT, AST, ALT) and creatine kinase. 4. Mean cholesterol concentrations with both drugs were significantly lower than with placebo, and the cholesterol‐ lowering effect was greater with simvastatin. There were no significant differences between treatment in EEG evoked potentials, HAD Scale, or DSST scores. On the sleep measure, subjects reported significantly greater difficulty in getting to sleep while on simvastatin than on pravastatin, but neither score differed from placebo. No significant correlations were observed between sleep ratings and either plasma cholesterol concentrations or EEG evoked potentials. 5. The study showed that, while both drugs reduced plasma cholesterol concentrations, neither exerted significant effects, compared with placebo, on EEG evoked potentials, mood, sleep, or cognitive performance after 4 weeks of chronic administration in healthy volunteers.