Abstract and Commentary
Commentary by M. Flint Beal, MD, Professor and Chairman, Department of Neurology, Cornell University Medical College, New York, NY, and Editor of Neurology Alert.
Synopsis: Atorvastatin reduces cholesterol levels and improves cognition in Alzheimer’s disease patients.
Source: Sparks DL, et al. Atorvastatin for the Treatment of Mild-to-Moderate Alzheimer’s Disease. Arch Neurol. 2005;62: 753-757.
There is substantial epidemiologic evidence that patients taking statins for the treatment of coronary artery disease have a reduced risk of Alzheimer’s disease (AD) later in life. Chronically elevated cholesterol levels in mid-life appear to increase later risk of AD. Furthermore, there are a number of animal studies that have shown that treatment with statins can reduce the generation of beta-amyloid, as well as amyloid plaques. This has been demonstrated in transgenic mouse models of AD, as well as in cholesterol-fed New Zealand white rabbits, which have evidence of increased brain beta- amyloid levels.
On account of this, a number of trials have been initiated to study the effects of statins in AD patients. The present report is of a small pilot study. The trial was a double-blind, placebo-controlled, randomized trial with a 1-year exposure to once daily atorvastatin at a dosage of 80 mg daily. Patients were randomized to either atorvastatin or placebo; 67 patients were randomized and 63 completed the 3-month visit. Substantially fewer subjects completed the full study. Only 46 individuals completed the 1-year study. The patients were well matched at baseline. They were matched for education, age, Apo E4 status, and initial values, on a number of cognitive scales. The primary outcome measures were the AD Assessment Scale-cognitive subscale and the clinical global expression of change scalescores. Secondary outcome measures included scores on the Mini-Mental state examination, geriatric depression scale, the neuropsychiatric inventory scale, and the AD cooperative study activities of daily living inventory. A tertiary outcome measure was the total cholesterol, as well as low density lipoprotein cholesterol.
The study showed that atorvastatin reduced circulating cholesterol levels. There was a significant improvement on the geriatric depression scale and the AD assessment scale cognitive subscale at 6 months. The other scales showed trends towards improvement, but they were not statistically significant.
Commentary
This was a small, double-blind trial of 80mg of the atorvastatin in AD subjects with mild-to-moderate impairment of cognitive function. It was intended as a pilot proof-of-concept study. It did show significant benefits in the cognitive scale at 6 months, however, these were not as marked at 9 months or one year. There was also a significant effect in the geriatric depression scale. The other scales also showed trends towards improvement. In view of the small number of subjects studied, this is very promising. Two much larger studies are underway studying the effects of statins in AD. It will be of great interest to determine whether these trials show any efficacy. — M. Flint Beal
Atorvastatin reduces cholesterol levels and improves cognition in Alzheimer’s disease patients.
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