Abstract
Statins are some of the most commonly prescribed drugs and are used to reduce blood cholesterol. Recent evidence suggests that, in some patients, they may adversely influence cognitive function including causing memory impairments. These clinical observations have led to statin prescriptions now including a warning about possible cognitive impairments. In order to better understand the relationship between statin treatment and cognitive function, studies in animals are needed. The present study investigated the effects of chronic treatment with two statins, pravastatin and atorvastatin, in two rodent models of learning and memory. Adult rats were treated once daily with pravastatin (10mg/kg, orally) or atorvostatin (10mg/kg, orally) for 18 days. Before, during and after treatment, animals were tested in a simple discrimination and reversal learning task. On the last day of treatment and following one week withdrawal, animals were also tested in a task of novel object discrimination. Pravastatin tended to impair learning over the last few days of treatment and this effect was fully reversed once treatment ceased. In the novel object discrimination task, pravastatin significantly impaired object recognition memory. No effects were observed for atorvostatin in either task. These data suggest that chronic treatment with pravastatin impairs working and recognition memory in rodents. The reversibility of the effects on cessation of treatment is similar to what has been observed in patients, but the lack of effect of atorvostatin suggests that lipophilicity may not be a major factor influencing statin-induced cognitive impairments.
Highlights
The class of drugs known as statins (3-hydroxy-3methylglutaryl-CoA [HMG-CoA] reductase inhibitors) are commonly prescribed to lower cholesterol in patients suffering from, or at risk of, cardiovascular complications [1]
Despite the evidence for positive effects of statin treatment on cognitive function in Alzheimer’s disease (AD), published case reports describe that some non-AD patients experience impairments of short term memory and amnesia during statin therapy that resolve with cessation of treatment [12,13]
There was no significant effect of treatment on the number of trials to criteria across the full study period (Figure 3, Table 1), there was a significant effect of day in both the simple discrimination (ANOVA: F11,231 = 3.91, P
Summary
The class of drugs known as statins (3-hydroxy-3methylglutaryl-CoA [HMG-CoA] reductase inhibitors) are commonly prescribed to lower cholesterol in patients suffering from, or at risk of, cardiovascular complications [1]. They are generally well tolerated in patients [2] and as such there is some support for the extension of statin treatment as a preventative therapy in people with healthy levels of cholesterol [3]. Despite the evidence for positive effects of statin treatment on cognitive function in AD, published case reports describe that some non-AD patients experience impairments of short term memory and amnesia during statin therapy that resolve with cessation of treatment [12,13]. A review of patients who self-reported memory or other cognitive problems associated with statin therapy, found evidence supporting a relationship between statin potency and significant negative impact on quality-of-life [15]
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