Dementia: Update for the Practitioner

There is interest in the idea that nonsteroidal anti-inflammatory agents may prevent or delay dementia. The data have uniformly suggested that these agents do not significantly affect the treatment of Alzheimer's disease. One report demonstrates quite clearly that neither the traditional nonsteroidals nor the COX-2 inhibitors have an effect on patients with Alzheimer's disease. Two studies in smaller populations suggested a trend but no significant benefit of traditional nonsteroidal drugs. Larger studies with anti-inflammatory agents show no benefit in Alzheimer's disease.

However, the question remains, is there an advantage to using these agents as a preventative mechanism? There are currently ongoing trials to address the question. It will require large sample sizes and a long time to answer that question.

There is significant evidence that lowering lipids is associated with a decrease in amyloid, which is associated with Alzheimer's disease. An animal study demonstrated a decrease in deposition of amyloid plaques in animals on a high-cholesterol diet when compared to animals with low cholesterol but comparable fat levels. These effects are reduced when the animal is treated with lipid-lowering agents.


	Hypercholesterolemia Accelerates Amyloid Deposit Number


	Hypercholesterolemia accelerates amyloid deposit number in mice, and the effect is reduced when the animal is treated with lipid-lowering agents. Courtesy of Dr. Mary Sano. Source of data: L. M. Refolo et al., "A Cholesterol-Lowering Drug Reduces Beta-Amyloid Pathology in a Transgenic Mouse Model of Alzheimer's Disease," Neurobiology of Disease 8, no. 5 (October, 2001): 890–99.

This, along with some epidemiological data, has led to the idea that a cholesterol-lowering class of drugs, known as statins, may have a benefit in slowing the progression of Alzheimer's disease. In fact, several clinical trials in both single-site groups and multiple-center groups are examining the cognitive effects of statins in Alzheimer's disease. There are also several studies examining cognitive effects in trials that have selected individuals with cardiovascular disease.

One of these trials is being conducted at Columbia University and other sites around the city. This study was originally one year in length, but it has been extended because we know of the importance of a longer trial. It will examine patients with Alzheimer's disease to determine whether or not the use of statins can slow the progression on cognitive and functional decline.

Cholinergic agents really do give us some hope that there would be benefit for patients with Alzheimer's disease, and clearly there are new mechanisms that have been proposed that will perhaps show wider benefit. There are a lot of challenges to developing these agents, including sample size and length of time of trial. However, we expect that we will come back to you in a year with newer data suggesting benefits and new approaches to treating Alzheimer's disease and mild cognitive impairment.

PREVIOUS | NEXT