AMSTERDAM – Elderly patients who received the highest total equivalent doses of high-potency statins, such as atorvastatin or rosuvastatin, had a threefold decrease in the risk of developing dementia, according to a retrospective, observational study in Taiwan.
Dr. Tin-Tse Lin, who presented the study at the annual congress of the European Society of Cardiology, said that the mechanism might be due to the statins’ effect on cholesterol reduction, antithrombotic activity, and their anti-inflammatory effect. The study, however, showed that lesser-prescribed lovastatin at a higher dose was positively associated with dementia development.
The findings add another piece to the statin-dementia puzzle and may alleviate some of the concerns with the so-called "brain fog" effect of statins, experts said.
Dr. Kim Williams Sr., chair of cardiology at Wayne State University, Detroit, said that the study "was very reassuring in that there was no real evidence of dementia with the statins that we tend to use, which are the more powerful ones." Older statins like lovastatin, however, are still of concern, said Dr. Williams, vice president of the American College of Cardiology, who was not involved in the study.
In 2012, the Food and Drug Administration added a warning to the statins’ label that the drugs could cause temporary memory loss and confusion. Meanwhile, several studies, including a 2012 review, have found no causality or conclusive relationship between statins and cognitive impairment.
Dr. Tin-Tse Lin
For the Taiwanese study, researchers used a random sample of 1,000,000 people covered by the country’s National Health Insurance. They identified nearly 58,000 patients who were older than 65 years of age and without a history of dementia in 1997 and 1998. The patients were followed up for an average of 4.5 years.
The study was divided into tertiles – low, medium, and high dosage – according to mean daily equivalent or total (across the entire follow-up period) equivalent dosage.
The primary endpoint was new diagnosis of presenile and senile dementia. Patients with vascular dementia were excluded.
More than 5,500 developed dementia. The remaining 52,000 patient served as controls.
Results showed that the adjusted hazard ratios for dementia were significantly inversely associated with increased total or daily equivalent statin dosage among the tertiles. For total equivalent statin dosage, the hazard ratios for dementia were 0.77 (low dosage), 0.63 (medium), and 0.33 (high), compared with controls, all significant differences. For mean equivalent daily dosage, HRs for dementia were 0.62, 0.70, 0.42, respectively, compared with controls, also significant differences.
The authors said that the protective effect of statins remained robust in different age, gender, and cardiovascular risk subgroups, with strong statistical trends.
Dr. Lin of the National Taiwan University Hospital, Hsin-Chu, Taiwan, said he did not know whether the findings would apply to other ethnicities.
He hypothesized that because disorders of cholesterol metabolism could lead to an increased incidence of cerebrovascular disease, and elevation of the cholesterol level may result in a high inflammatory status associated with neurodegeneration, "I think it is reasonable to say that statins may facilitate lowering the risk of dementia."
Prof. Terje R. Pedersen of the University of Oslo (Norway), who commented on the study, said that "It is implausible that statins have any impact on progression of Alzheimer’s disease, but it might be plausible to think that when you prevent extensive atherosclerosis, then you also prevent dementia."
The bottom line, said Dr. Williams, is that the study "adds another dimension to the idea that the stronger statins that are used in the highest doses have the best benefit. That’s certainly true for the cardiovascular risk and now with dementia prevention."
Dr. Lin and Dr. Williams had no relevant disclosures. Prof. Pedersen has received research grants from Merck and Pfizer; consultation fees from Merck, AstraZeneca, Pfizer, and Amgen; speaker honoraria from Merck, Pfizer, AstraZeneca, Roche, Novartis, Amgen, and GlaxoSmithKline.
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