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 score indicates more depressive symptoms.