As we get older, our memories fade. In most of us there is a gradual decline in memory--from 6% to 10% per decade--beginning at about age 30.
But others suffer from a loss greater than expected, and are diagnosed as having age-associated memory impairment. This condition is not nearly as dramatic as senile dementia and Alzheimer's disease, but it nonetheless affects the person's day-to-day life.
Now, researchers at several institutions, including Stanford University, are testing a new drug that seems to have positive effects on such learning and memory deficiencies and may be an important step on the road to a treatment for Alzheimer's, the memory-destroying condition that devastates the lives of as many as 10% of people over 65.
The drug being tested is BC-PS (bovine cortex phosphatidylserine), a naturally occurring brain chemical derived from cow brains. Results of preliminary studies of the drug were presented recently at a meeting sponsored by the National Institute of Mental Health and have been submitted to the journal Neurology.
BC-PS seems to work by slowing or perhaps reversing some of the neurochemical changes that occur in the brain with age.
One of the most obvious changes as the brain ages is the diminished activity of acetylcholine, a neurotransmitter involved in learning and memory. It has been known since 1961 that certain sedatives inhibit the activity of acetylcholine and interfere with learning and memory. And it was discovered in 1976 that acetylcholine levels are severely diminished in the brains of Alzheimer's patients. Studies of rats and monkeys show that BC-PS raises the level of acetylcholine in the brain.
The most recent studies of about 150 people were conducted by the psychiatry departments at Stanford and Vanderbilt universities and at Memory Assessment Clinics in Bethesda, Md. All the subjects, whose average age was 64, were evaluated with computerized memory assessment tests and found to have age-associated memory impairment, said Thomas H. Crook, president of Memory Assessment Clinics. In general, they had trouble remembering everyday things such as their subway stop and telephone numbers.
After the initial evaluation, half the people began taking daily doses of BC-PS while the rest received a placebo. They were then retested at four-week intervals, taken off the drug after 12 weeks and tested again three weeks later.
Even though few of those taking the drug reported dramatic changes in their memory, test results showed that they had improved significantly (up to about 15% over their original test results) compared to those taking the placebo. "That isn't miraculous," Crook said, "but it is improvement, and it was consistent improvement, particularly in the more severely impaired people."
Crook, who has tested hundreds of drugs for most of the major pharmaceutical companies working on memory and cognitive problems, said, "This is the first time we have seen anything this effective." Jared Tinklenberg, who conducted the study at Stanford, agreed. "What makes this exciting," he said, "is that we did our study independent of the other two groups, and we all came up with more or less the same thing."
BC-PS was developed and tested in Europe over the last several years, primarily by FIDIA Research Laboratories, one of Italy's largest pharmaceutical firms. According to their researchers, BC-PS not only increases acetylcholine activity but may work by acting on nerve cell membranes.
By replacing a lost brain chemical called phospholipids, FIDIA researchers suggested, the drug restores the cell membrane fluidity that appears to be altered in the brains of Alzheimer's victims.
Another possible mechanism involves the deterioration of certain cells in the hippocampus, an area of the brain intimately involved in the regulation of cognitive functions. This deterioration can be seen and measured in the brains of aged rats and can be used as a tool to monitor the effects of drugs. FIDIA researchers report that the brains of aged rats treated with BC-PS look just like those of younger animals and show none of the deterioration seen in older, untreated animals. The treated animals also display significantly improved memory on a variety of tasks.
Perhaps in a year or so, according to Crook, the drug may be available in the United States to treat certain types of memory loss, including age-associated memory impairment. "There are a tremendous number of people who are not demented but who have really quite clear memory problems," Crook said. "I don't think this or any other drug is going to rejuvenate them in the sense that they will perform as well as 25- or 30-year-olds, but it could reverse some of their deficit and help them perform as well as they did five or 10 years earlier."
Barry Lebowitz, chief of mental disorders of the Aging Research Branch at the National Institute of Mental Health, has reviewed Crook's findings and said, "When someone like Crook, who has tested dozens of drugs, reports positive findings, there must be something there." Crook does not expect BC-PS to be effective with the most severe cases of Alzheimer's--perhaps because too much brain damage has already occurred. But it may help people in the early stages.