Dr Lin said: "Statins are widely used in the older population to reduce the risk of cardiovascular disease. But recent reports of statin-associated cognitive impairment have led the US Food and Drug Administration (FDA) to list statin-induced cognitive changes, especially for the older population, in its safety communications."
He added: "Previous studies had considered statin therapy to exert a beneficial effect on dementia. But few large-scale studies have focused on the impact of statins on new-onset, non-vascular dementia in the geriatric population."
Accordingly, the current study examined whether statin use was associated with new diagnoses of dementia. The researchers used a random sample of 1 million patients covered by Taiwan's National Health Insurance. From this they identified 57,669 patients aged >65 years who had no history of dementia in 1997 and 1998. The analysis included pre-senile and senile dementia but excluded vascular dementia.
There were 5,516 new diagnoses of dementia during approximately 4.5 years of follow-up. The remaining 52,153 patients aged >65 formed the control group. Subjects were divided into tertiles according to their mean daily equivalent1 dosage and total (across the entire follow up period) equivalent dosage.
The adjusted hazard ratios (HRs) for dementia were significantly inversely associated with increased daily or total equivalent statin dosage. The HRs for the three tertiles of mean equivalent daily dosage (lowest to highest) were 0.622, 0.697 and 0.419 vs control (p<0.001 for trend). The HRs for the three tertiles of total equivalent dosage (lowest to highest) were 0.773, 0.632 and 0.332 vs control (p<0.001 for trend). The protective effect of statins remained in different age, gender and cardiovascular risk subgroups.
Dr Lin said: "The adjusted risks for dementia were significantly inversely associated with increased total or daily equivalent statin dosage. Patients who received the highest total equivalent doses of statins had a 3-fold decrease in the risk of developing dementia. Similar results were found with the daily equivalent statin dosage."
He added: "It was the potency of the statins rather than their solubility (lipophilic or hydrophilic) which was a major determinant in reducing dementia. High potency statins such as atorvastatin and rosuvastatin showed a significant inverse association with developing dementia in a dose-response manner. Higher doses of high potency statins gave the strongest protective effects against dementia."
Dr Lin continued: "The results were consistent when analysing daily doses of different kinds of statins. Almost all the statins (except lovastatin) decreased the risk for new onset dementia when taken at higher daily doses. A high mean daily dosage of lovastatin was positively associated with the development of dementia, possibly because lovastatin is a lipophilic statin while the anti-inflammatory cholesterol lowering effect of lovastatin is not comparable to that of atorvastatin and simvastatin."
Dr Lin concluded: "To the best of our knowledge, this was the first large-scale, nation-wide study which examined the effect of different statins on new onset dementia (except vascular dementia) in an elderly population. We found that high doses of statins, particularly high potency statins, prevent dementia."
Notes
1. Equivalent dosages are used when comparing the effects of different drugs. Each statin was assigned an appropriate equivalent dose according to the following formula: lovastatin 40mg = pravastatin 40mg = simvastatin 20mg = atorvastatin 10mg = fluvastatin 80mg = rosuvastatin 5mg.
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