Cholesterol-Lowering Drug May Slow Alzheimer’s Progression

NEW ORLEANS, LA. — The cholesterol-lowering drug atorvastatin slowed down mental decline and improved depressive symptoms in people with Alzheimer’s disease, according to a small pilot study reported at the American Heart Association’s Scientific Sessions 2004.

“This is the first off-label use of a drug tested in Alzheimer’s patients in the last ten years that has shown promise of benefit,” said D. Larry Sparks, PhD, senior scientist and head of the Roberts Laboratory for Neurodegenerative Disease Research at Sun Health Research Institute in Sun City, Ariz.

Animal and human studies have shown that elevated cholesterol is an important risk factor for Alzheimer’s disease. Based on this research and Dr Sparks’s work for the past 20 years, he and colleagues in Bethesda, Md., New York City, Phoenix and Sun City, tested the effects of lowering cholesterol in people with mild-to-moderate Alzheimer’s disease.

The Alzheimer’s Disease Cholesterol-Lowering Treatment Trial (ADCLT) was a double-blind, placebo-controlled pilot study that assessed whether lowering cholesterol with atorvastatin could stabilize or improve cognition in people with mild-to-moderate Alzheimer’s. Doctors administered the statin drug in addition to the cholinesterase inhibitors the patients were already taking.

Cholinesterase inhibitors are the only Food and Drug Administration-approved therapy for mild-to-moderate Alzheimer’s disease. The drugs inhibit the breakdown of acetylcholine, a transmitter that is decreased in Alzheimer’s patients and thought to be related to mental decline.

The researchers evaluated 46 patients — 25 on atorvastatin 80 mg and 21 on placebo — for one year. The participants were, on average, 78 years old with 14 years of education. One-third of the group was female. The patients were evaluated periodically for cognition, overall mental function, and depression. Alzheimer’s patients are known to have depression that usually gets worse as their Alzheimer’s disease progresses.

Fifty-three percent of the atorvastatin-treated group improved or stabilized while 28 percent of those taking placebo improved or stabilized. After a year, the patients on atorvastatin exhibited a significant improvement in their symptoms of depression, as measured by GDS, while the placebo group showed a decline. Atorvastatin decreased low-density lipoprotein, known as “bad” cholesterol, by more than 50 percent from 124 milligrams per deciliter (mg/dL) to 57mg/dL. Total cholesterol dropped by more than 40 percent (from 210 mg/dL to 130 mg/dL).

“These findings are important because the data show that statin treatment works in excess of the only currently approved therapy for Alzheimer’s disease,” Dr Sparks said. “This may prove that two drugs work better than one alone. There are larger, multicenter trials in progress to confirm these findings.”

The study was funded by the Institute for the Study on Aging and by Pfizer. Pfizer supplied study medication.

American Heart Association Scientific Sessions is held annually each November, lasts three and a half days, and offers comprehensive education in the pathophysiology, diagnosis, treatment, and prevention of cardiovascular disease. Total attendance of the American Heart Association’s 77th Scientific Sessions in New Orleans is projected at nearly 30,000, including close to 20,000 scientists, cardiologists, internists, researchers, family practitioners, surgeons, nurses, and other medical professionals from throughout the world.