Statins Fail to Prevent Dementia, Alzheimer's Disease

Janis Kelly

April 15, 2009

April 15, 2009 — High serum cholesterol may contribute to the development of Alzheimer's disease (AD) and vascular dementia, but lowering cholesterol levels with statins does not prevent these problems, according to a new Cochrane review.

"The most important point is that we did not find any effect on dementia prevention from use of statins," lead author Bernadette McGuinness, MD, MRCP, from the Queen's University of Belfast, in the United Kingdom, told Medscape Psychiatry.

"Statins have a variety of uses and are very important in cardiovascular disease, but unfortunately they did not appear efficacious in preventing dementia. The studies included were very large, with approximately 26,000 participants in total, so if an effect were present one would have seen it. The patients were also at high vascular risk and so would have been at increased risk of developing dementia," she said.

Some researchers had hoped that statins would lower the risk for dementia because epidemiological studies have linked elevated cholesterol and Alzheimer's disease and because studies in animal models showed that reducing cholesterol decreased Alzheimer's-like symptoms.

The review, an update to an earlier review completed in 2001, comprised 26,340 participants in 2 major studies. One study, the Medical Research Council (MRC)/British Heart Foundation Heart Protection Study (HPS), looked at simvastatin use in 20,536 patients and followed them for 5 years. The other study, the PROSPER trial, looked at pravastatin use in 5804 patients, with an average follow-up of 3.2 years.

Both studies were double-blind, randomized, placebo-controlled trials of statin medications in individuals at risk for dementia and AD. Taken together, the studies included adults between the ages of 40 and 82 years.

Lack of Effect "Surprising"

“We were surprised at the lack of effect of statins in preventing dementia. Biologically, it seemed feasible they could, and the initial observational and cohort studies were very promising. There are problems with these types of studies (such as indication bias), which demonstrates why it is important to carry out randomized controlled trials," Dr. McGuinness said.

"The number of patients who developed dementia was very low in both studies, which was also surprising, given their age and vascular risk," Dr. McGuinness added. "This may relate to careful control of vascular risk factors, as was seen in previous vascular dementia trials, or may be that the screening used to detect dementia in the trials was not sensitive enough. This may be particularly important for the MRC/HPS trial, where just a telephone interview was used."

The researchers concluded that statins given in late life to individuals at risk for vascular disease do not protect against dementia. The review authors found no difference between patients receiving the medications and patients receiving placebo with respect to incidence of dementia, cognitive function, or performance on specific neuropsychological tests.

Howard Fillit, MD, executive director of the Alzheimer's Drug Discovery Foundation, in New York, said that although there is little conclusive evidence that statins are useful in the treatment of dementia, some epidemiologic data suggest that they may be preventive.

"However, most patients with Alzheimer’s do not have 'pure' AD but have multiple comorbidities that may contribute to dementia, including vascular comorbidities that should be addressed if high cholesterol is present and treatment is indicated in any event to prevent cardiovascular disease and/or stroke," Dr. Fillit said.

Safety Concerns

Whether statins given in middle age for many years can protect against dementia in later life is unknown and perhaps unknowable. "Clinical studies in middle-aged patients followed for many years would be useful but may not be feasible. It may be that one needs to take a statin for many years before any benefit in prevention is seen. Clinical studies of statins in treatment of dementia are still largely unpublished and awaited. We are also carrying out a Cochrane review on that topic," Dr. McGuinness said.

Dr. Fillit would like to see a trial of statins in patients with high cholesterol who are at risk for stroke to see if such treatment prevents dementia — either vascular or AD.

Long-term use of statins to prevent dementia also raises some safety concerns. "Statins have a range of mechanisms that could help or hurt cognition," said Beatrice Golomb, MD, PhD, from the University of California, San Diego. "Regarding statins as preventive medicines, there are a number of individual cases in case reports and case series where cognition is clearly and reproducibly adversely affected by statins."

Dr. Golomb also said that some randomized trials have shown that the net effect of statin medications was significantly adverse and others that have shown it was neutral but that none has shown statin use to be favorable for cognition.

Study coauthor Peter Passmore, also from the Queen's University of Belfast, discloses that he was an investigator in the Leade study and received grants from Pfizer, Merck Sharp & Dohme, Bristol-Myers Squibb, and Novartis and honoraria from Pfizer, Merck Sharp & Dohme, Novartis, and AstraZeneca.

Cochrane Database Syst Rev. 2009;1:CD007514.