No clear-cut answers on statins as therapy for Alzheimer's disease
Research shows mixed, conflicting results, and the complexity of this open-ended scientific question.
Philadelphia, July 2004 – Statins continue to generate interest as a possible preventive strategy for Alzheimer's disease, based on studies at The 9th International Conference on Alzheimer's Disease and Related Disorders (ICAD), presented by the Alzheimer's Association.
Ling Li, D.V.M, Ph.D., of the University of Alabama at Birmingham, reports that simvastatin (Zocor, Merck) helps mice with memory problems. Mice genetically engineered to mimic key aspects of Alzheimer's disease have trouble remembering their way through mazes as they age. Li finds that Alzheimer mice treated with simvastatin regain their ability to navigate mazes and that the drug improves performance even for the non-engineered mice in the control group.
Other studies demonstrate the complexity of emerging data on statins.
- Richard B. Parsons, Ph.D., of London's St. Georges Hospital, finds that four different statins reduce, to varying extent, brain cells' production of a protein fragment thought to play a key role in Alzheimer's, with fluvastatin (Lescol, Novartis) being the most effective. Initially, the drugs all increase the amount of the fragment released by cells but long-term use of statins in patients would lead to a decrease in the overall amount released.
- Kina Hoeglund, M.Sc., of Sweden's Göteborg University, reports that statins have mixed effects on marker molecules in blood and spinal fluid that may track the severity of Alzheimer's disease.
- P. Murali Doraiswamy, M.D., Director of Psychiatry Clinical Trials at Duke, systematically analyzed all existing randomized controlled trials of statins in people without dementia (comprising over 30,000 participants) and found no evidence yet that any statin protects against cognitive decline. In a second, small study of elderly people at risk for dementia, Doraiswamy and colleagues report that rates of brain tissue shrinkage, measured using a special MRI scan, were no different between statin users and nonusers.
John C. S. Breitner, M.D., of VA Puget Sound Health Care System and the University of Washington, reported new data that argue against the use of statins for Alzheimer prevention. Although several observational studies suggested that people taking statins had a significant reduction in their risk of developing Alzheimer's, Breitner described new results from three, long-running population studies that assess the possible impact of statins on preventing Alzheimer's.
"If you look at a 'snapshot' of statin users compared with non-users at a single moment in time, statin users seem to have a lower risk of Alzheimer's," Breitner said. "But if you look at people taking statins at enrollment in these studies and follow them over several years, the benefit of statins in warding off dementia largely disappears."
Large-scale clinical trials are needed to resolve the questions raised by these studies. Trials currently underway include (also see http://www.clinicaltrials.gov):
- Cholesterol Lowering Agent to Slow Progression (CLASP) of Alzheimer's Disease Study. Sponsored by the National Institute on Aging (NIA), CLASP is investigating the safety and effectiveness of simvastatin to slow the progression of Alzheimer's.
- The Effect of Short-Term Statin and NSAID Treatment on CSF Beta-Amyloid. To determine whether short-term use of ibuprofen and lovastatin (Mevacor, Merck) affects levels of the abnormal protein beta-amyloid in people at risk for developing Alzheimer's. Sponsored by the National Institute of Mental Health (NIMH)
- LEADe Study. Sponsored by Pfizer, Inc., this study is comparing the efficacy and safety of atorvastatin (Lipitor) in combination with donepezil (Aricept) in patients with mild to moderate Alzheimer's.
"Our current situation with regard to statins and Alzheimer's disease prevention is a classic 'open question' moment in science," says William H. Thies, Ph.D., Alzheimer's Association vice president, Medical & Scientific Affairs. "The question to be resolved is: Do statins reduce an individual's risk of developing Alzheimer's disease if you prescribe them specifically for that purpose before a person shows any detectable symptoms of dementia?
"Although current data are mixed, there has been promising evidence of some biological mechanisms that may account for the preventive benefit. Almost everyone agrees that the data are good enough to justify large-scale trials. Statins are just one good example of why the Alzheimer's Association is calling on Congress to earmark additional funds for Alzheimer's disease clinical trials," Thies said.
The 9th International Conference on Alzheimer's Disease and Related Disorders (ICAD), presented by the Alzheimer's Association, is the largest gathering of Alzheimer researchers in history. More than 4,500 scientists from around the world will present and discuss the findings of 2,000 studies showcasing the newest treatment advances in Alzheimer's disease and steps toward prevention. ICAD will be held July 17-22, 2004, at the Pennsylvania Convention Center in Philadelphia, Pennsylvania.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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