Cholesterol-lowering drug may slow Alzheimer's progression

November 09, 2004

NEW ORLEANS, Nov. 9 - 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 10 years that has shown promise of benefit," said D. Larry Sparks, Ph.D., 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 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.

Quarterly, the investigators administered the Mini-Mental State Examination (MMSE), the gold standard for measuring global function; the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-cog), a cognitive function test; and the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), which captures a clinician's perception of change.

Semiannually, they examined participants using the Neuropsychiatric Inventory (NPI) and ADCS-ADL, which measures activities of daily living. They administered the Geriatric Depression Scale (GDS) at the start of the study and at the final visit. Levels of cholesterol, the protein ceruloplasmin, the gene apolipoprotein E, and the antioxidant superoxide dismutase were evaluated quarterly.

At the start of the study, average ADAS-cog scores for both groups was 20. After one year, the average score in patients taking atorvastation was still about 20. The average score in the placebo group was 24, indicating a decline (higher number indicates worse performance).

GDS scores were an average of 6 in both groups at the start of the study. After a year, the atorvastation group averaged a score of 4, while the placebo group averaged an 8, again indicating a decline. A higher GDS scores indicates more depressive symptoms.

MMSE scores started at 20.8 in both groups. Higher scores reflect a high performance. Those taking atorvastatin remained about the same at 20.4, but the average score among the placebo group declined to 18.

The average NPI score was 7.5 in both groups at the start of the study. After a year of treatment, the atorvastatin group declined to an average score of 9. However, the placebo group score declined even farther to 16. NPI is a total score. A greater number indicates more severe symptoms.

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," Sparks said. "This may prove that two drugs work better than one alone. There are larger, multi-center trials in progress to confirm these findings."

Co-authors are Marwan N. Sabbagh, M.D., Donald J. Connor, Ph.D., Lenore J. Launer, Ph.D., Suzana Petanceska, Leslie Baxter, Patrick Browne, M.D., Jean Lopez, R.N., MSN., Dawn Wassar Pharm. D., Jeff Lochhead M.S., and Chuck Ziolwolski, M.S.
The study was funded by the Institute for the Study on Aging and by Pfizer. Pfizer supplied study medication.

Statements and conclusions of study authors that are published in the American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect association policy or position. The American Heart Association makes no representation or warranty as to their accuracy or reliability.

Abstract 3756

American Heart Association

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