Govt. Ups Ante to Improve Alzheimer’s Treatment

The Alzheimer’s Disease Cooperative Study (ADCS) has received $54 million in funding from the National Institute on Aging (NIA) as the institute focuses on expediting the search for effective diagnostic tools and screening for the progressively debilitating disease.

Coordinated by the University of California at San Diego (UCSD), the ADCS will use its network of 83 sites across the U.S. and Canada not only to study ways to improve diagnosis of Alzheimer’s but also to test new medications aimed at preventing the disease or slowing down its progression.

The ADCS network was formed in 1991 as a collaboration between the institute and UCSD. In its first 10 years, ADCS put in place an infrastructure of researchers to carry out clinical trials of new therapies for Alzheimer’s, developed new and more reliable ways to evaluate patients enrolled in these and other studies, and undertook a number of clinical trials.

The new award, a five-year grant, will allow that work to continue and move treatment research in new directions, including studies of the cholesterol-lowering drugs called statins, antioxidants, and high-dose vitamin regimens, according to ADCS project officer Neil Buckholtz, Ph.D., chief of the Dementias of Aging Branch at the NIA.

“Basic and epidemiological studies over the past few years have given us important clues about compounds that might prove more effective against Alzheimer’s,” Buckholtz said in a prepared statement announcing the award. “This award will help us test out a number of these possibilities quickly and reliably so that we can give clinicians, patients, and families new weapons in the fight against Alzheimer’s disease.”

According to Leon Thal, M.D., chair of the department of neurosciences at UCSD School of Medicine and the ADCS principal investigator, about 2,500 people have participated in 13 ADCS research protocols over the past decade. Those studies have looked at the use of vitamin E, the Parkinson’s disease drug selegiline, and estrogen, among others.

The efforts over the next five years will continue some of these studies and pursue new protocols as well:

• Vitamin E and donepezil: This ongoing trial, aimed at prevention, began in 1999. It is looking at whether vitamin E, an antioxidant, or donepezil, an acetylcholinesterase inhibitor, may prevent the progression of patients with mild cognitive impairment to full Alzheimer’s. The study includes about 700 patients.

• Statins: This new study will explore the suspected link between cholesterol and the development of Alzheimer’s. Some research has indicated that patients who have mild cognitive impairment or early Alzheimer’s and are taking these cholesterol-lowering medications have lower rates of progression to full Alzheimer’s. This study will address the question in a systematic way.

• High-dose folate/B6/B12 supplements: This 18-month clinical study will examine whether these B-complex vitamins can reduce blood levels of homocysteine, which has been shown to be elevated in some AD patients. By reducing levels of homocysteine, researchers hope to be able to slow progression of cognitive decline in AD patients.

• Valproate: In this two-year clinical trial, ADCS researchers will evaluate whether this anticonvulsant/mood stabilizing medication can delay the emergence of agitation and psychosis in Alzheimer’s patients. Recent research on this common drug, used for many years in patients with epilepsy and increasingly over the last decade in patients with bipolar disorder, has significant neuroprotective properties.

• Indole-3-Propionic Acid (IPA): In a stage I clinical trial, researchers will look at the safety and tolerability of IPA in patients with Alzheimer’s. IPA is known to be a highly potent, naturally occurring antioxidant. It also has been shown to interfere with the action of enzymes that contribute to the formation of amyloid plaques.

• Improved assessment measures: Ongoing studies are developing new and improved measures for evaluation of the clinical effectiveness of drugs that are being tested for both prevention and treatment of AD.

More information on clinical research on Alzheimer’s is posted on the Web at www.nia.nih.gov and http://adrc.ucsd.edu. ▪