Statins for the prevention of dementia

Apr 14 2009

An increasing number of studies show that elevated serum cholesterol levels might be part of the cause of Alzheimer's disease, but a new review of studies says that, even so, the most successful class of cholesterol-lowering medicines will not stave off the condition.

Statins includes medications such as atorvastatin (Lipitor) and pravastatin (Pravachol), which are some of the best-selling drugs in the world.

The drugs lower cholesterol by inhibiting a key enzyme used by the body to make it, which decreases cholesterol formation and helps reduce the amount of low-density lipoprotein (LDL or "bad" cholesterol).

Biomedical and epidemiological studies showing the relationship between elevated cholesterol and Alzheimer disease have caused scientists to wonder if these medications could lower the risk of developing the disease, which is the most common cause of dementia. For example, in studies using animals, the expression of Alzheimer symptoms slowed with lowered cholesterol, giving hope that the same might be true for humans.

The new review appears in the latest issue of The Cochrane Library , a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews like this one draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

"From these trials, which contained very large numbers and were the gold standard … it appears that statins given in late life to individuals at risk of vascular disease do not prevent against dementia," said lead study author Bernadette McGuinness, a senior clinical research fellow in geriatric medicine at Queen's University in Belfast, Ireland. "I feel the follow-up time was sufficient to allow for an effect to appear," she added.

The review, an update to an earlier review completed in 2001, comprised 26,340 participants in two major studies. One study, the Medical Research Council/British Heart Foundation Heart Protection Study (HPS), looked at simvastatin (Zocor) use in 20,536 patients and followed them for five years. The other study, the PROSPER trial, looked at pravastatin use in 5,804 patients, with an average follow-up of 3.2 years.

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

While the review showed no evidence that statin medications were harmful to cognition, the review authors found no difference between patients receiving the medications and patients receiving placebo medications when it came to incidence of dementia, cognitive function or performance on specific neuropsychological tests, such as a picture word learning test.

"Statins have a range of mechanisms that could help or hurt cognition," said Beatrice Golomb, M.D., of the department of family and preventive medicine at 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."

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.

McGuinness said that while the two large trials showed that statins given later in life do not protect against dementia, "it is unclear, however, if statins given in middle age for many years can protect against dementia in later life, as the studies did not address this."

She noted that neither study aimed to assess the prevention of dementia primarily; in fact, dementia was at most a secondary outcome in the studies. As a result, "some people with dementia may not have been picked up by the screening, especially in HPS, but it is difficult to know."

Patients taking statins might not take them reliably if they've developed cognitive problems or side effects, Golomb said. "That is, the very patients who develop cognitive problems or adverse effects as a result of statins will be less compliant on statins, the literature says, and then may be selectively excluded from the study." As a result, the study could portray unrepresentatively favorable results where cognitive function is concerned, she said. "However, the conclusion, an important one, remains largely correct."

The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit http://www.cochrane.org for more information.

McGuinness B, et al. Statins for the prevention of dementia. Cochrane Database of Systematic Reviews 2009, Issue 2.