E-longating survival and function

E-longating survival and function

Alzheimer's disease, the most common form of dementia, afflicts roughly 4 million people in the United States alone. It strikes 10 percent of persons by age 65, and nearly half of all persons over 85. Currently, it ranks third only to heart disease and cancer in how much is spent to care for its sufferers?at least $100 billion annually.

Though two drugs have been approved in the United States to treat this scourge, tacrine and donepeziol, neither targets the processes behind the loss of brain neurons and synapses that rob Alzheimer's victims of their memories and dignity. It's against this backdrop that researchers from 23 Alzheimer's disease cooperative-study sites report promising?if limited?news this week about the prospects for vitamin E in slowing this dementia's advance.

Previous studies had indicated that the type of nerve damage and brain cell losses incurred by persons with Alzheimer's may stem at least in part from exposure to oxygen-derived free radicals, biologically damaging molecular fragments that form naturally in the body. So for 2 years, the scientists administered antioxidants to 257 of the 341 persons that they were studying with moderately severe Alzheimer's. Until the study was over, no one knew whether the study's volunteers were receiving one of the treatment regimens or inactive look-alike pills.

In the April 24 New England Journal of Medicine, Mary Sano of Columbia University and her colleagues now report that men and women who had received either high doses of vitamin E (1000 International Units twice a day), a prescription drug call selegiline, or both, experienced a significant slowing in functional declines when compared to those who received no medicine.

All three treatment regimens delivered similar results, about a 7-month delay in the time it took a patient to reach any of four major milestones of deterioration: death, a required move into a nursing home, loss in the ability to perform major activities of daily living (such as grooming, feeding oneself, or using the toilet), or a progression to severe dementia. Unfortunately, none of the treated groups exhibited any difference in tests of mental function?either over time or when compared to untreated patients.

"We are very excited that the study showed not only that the clinical signs of disease progression can be slowed, but also that for the first time drugs were effective with people in the moderately severe stages of the disease," says Edward Truschke, president of the Alzheimer's Disease and Related Disorders Association. While he says that "it is premature to actually recommend vitamin E or selegiline as a specific treatment for Alzheimer's disease without additional, confirming research," he also adds that owing to the vitamin's other many well-demonstrated benefits, "there appears to be no reason not to take [it] in moderation."

Tempered enthusiasm by others

The antioxidant findings "are encouraging but should be viewed cautiously," argue David A. Drachman of the University of Massachusetts Medical Center and Paul Leber of the Food and Drug Administration. Together, they authored an editorial that accompanied the new paper.

In it, they note that impaired memory and failing mental faculties "are cardinal clinical effects of Alzheimer's disease and are usually the primary outcome measure in therapeutic trials." So, they observe, "if the drugs truly slowed deterioration, their failure to affect the scores on [cognitive tests] is perplexing. Perhaps the treatment effect was only symptomatic, affecting behavior but not the underlying disease."

Then, there is the issue of statistics. Even the rare physician who is familiar with the methods used in this study "may have trouble assessing the validity of the results," they argue. "Questions arise because statistical adjustments had to be made, the details of the statistical methods are too sparse to assess, and the size of the effect is unclear."

They also raise a host of issues related to the outcomes chosen for study and how they were compared. For instance, when the study began, nearly one in five patients already needed assistance with at least one of the baseline daily-living activities?grooming, feeding, or toilet use. Since one of the measured milestones was a patient's need for assistance in two of these categories, Drachman and Leber contend that patients who started halfway to this endpoint should not be compared to those who were not yet approaching it.

However, they conclude, "in the absence of a treatment with a major effect, treatments that have even small benefits may provide some directions for future therapy." In the long term, these researchers suspect, more powerful analogs of vitamin E and the other drug may be developed and used as part of a cocktail of different drugs to slow or arrest Alzheimer's ravages.

For now, they concede, physicians or family members may want to try one of the agents tested here on the Alzheimer's patients that they care for. These individuals may also want to experiment with dietary modifications suggested by a Dutch team at Erasmus University. Earlier this year, they reported that men who ate diets rich in fish, linoleic acid, and various antioxidants exhibited fewer cognitive impairments than did men who eschewed such nutrients (Quite literally, some food for thought).

References:

Drachman, D.A., and P. Leber. 1997. Treatment of Alzheimer's disease?searching for a breakthrough, settling for less. New England Journal of Medicine 336(April 24):1245.

Sano, M., et al. 1997. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. New England Journal of Medicine 336(April 24):1216.