After creeping corpulence, perhaps the most common complaint people have about growing older is what the experts politely call “benign” memory loss and the rest of us, less politely, sometimes call CRS, for Can’t Remember You-Know-What.
For men with sluggish memories, the best advice to slow the aging process is tried and true: Exercise (to increase blood flow to the brain); stay mentally active (to enhance connections between brain cells); take nonsteroidal anti-inflammatory drugs such as ibuprofen, vitamin E, and maybe a little gingko (though the data on gingko are less compelling).
For women past a certain age, however, there’s one more potentially powerful option – estrogen, a hormone that is increasingly being touted as a way to ward off not only normal age-related memory loss but Alzheimer’s disease as well.
The bio-logic behind estrogen’s surging popularity as a memory enhancer is respectable. Estrogen improves connections between nerve cells in the brain and enhances cerebral blood flow. It boosts important brain chemicals such as serotonin, acetylcholine and dopamine, and acts as an antioxidant, too, blocking other chemicals that otherwise would damage brain cells.
Even before the memory connection was made, of course, many women were already convinced of estrogen’s virtues: Hormone therapy is a huge industry that’s likely to grow to as much as a $5 billion market by 2005, based on estrogen’s proven ability to reduce menopausal symptoms such as hot flashes and to prevent osteoporosis.
But does it really work on the brain? The answer, unfortunately, depends on whom you ask, how you measure memory, and, perhaps most importantly, whether the researcher conducts actual experiments or simply surveys older women about their memories and estrogen use.
For the moment, the best guess is that estrogen seems to protect against some kinds of normal memory loss and may help prevent Alzheimer’s disease as well. But it probably does no good at all, at least without other drugs, once Alzheimer’s is already established.
One of the key research problems is that “there is no one, unitary thing called memory,” said Patricia Tun, associate director of the memory and cognition lab at Brandeis University in Waltham. And that, said Dr. Elizabeth Barrett-Connor, a professor of family and preventive medicine at the University of California at San Diego, means “nobody knows exactly what to test for.”
While some kinds of memory decline with age, some – such as vocabulary – actually get better with the years, Tun noted. Estrogen is probably not going to turn out to be a panacea for memory, she said, because men and women show similar patterns of memory change as they age, even though only women experience sharp declines in estrogen at menopause.
Nonetheless, there is a growing body of evidence suggesting that estrogen does play some role in protecting memory and enhancing learning, said Susan Resnick, a neuro-psychologist at the National Institute on Aging. “From our studies, we know that women who use estrogen perform better on memory tests than women who don’t.”
Indeed, recent studies by Resnick and others using brain-imaging technology – not just clinical tests of memory – are encouraging; they show that estrogen seems to affect blood flow to areas of the brain such as the hippocampus, which is known to be involved with memory.
Intensive research on estrogen and memory began more than a decade ago, when researchers in Western Ontario showed that premenopausal women performed better on tests of certain cognitive skills – like being able to pronounce tongue-twisters fluently – during the part of their menstrual cycles when levels of natural estrogen were highest.
In postmenopausal women, too, Barbara Sherwin, a psychologist at McGill University in Montreal, has shown that “scores on tests of memory are better for estrogen-users than nonusers.”
In several randomized studies, Sherwin tested women who were scheduled for surgery to remove their ovaries, which make estrogen, and uteruses. The women were then assigned either to receive estrogen supplements or not. Those who took estrogen were able to maintain their pre-surgery scores on tests of memory, while those who did not showed declines.
In general, Sherwin said, estrogen seems better at protecting verbal memory than visual memory. But last April, a randomized study published in Psychopharmacology suggested estrogen may enhance visual memory, too. Women ages 55 to 75 who had never taken hormone therapy before were assigned either to wear an estrogen skin patch or not for three weeks. And those who did showed benefits in remembering things they had seen.
In addition to such randomized studies, there have been a number of observational studies that don’t assign women to take estrogen or not but simply follow them over time, test their memories and correlate that with estrogen use. These studies are more difficult to interpret.
In one such study, Barrett-Connor of San Diego found no effect of estrogen on awareness and judgment, even though her team used 12 different types of memory tests. The study of about 3,000 women was published in 1993 in the Journal of the American Medical Association.
Last year, an observational study of more than 21,000 women ages 70 to78 – the Nurses’ Health Study – also found no significant differences on several cognitive tests between estrogen users and nonusers, though the estrogen users did have an advantage in verbal fluency.
On the plus side, an observational study of more than 700 women in New York City published in 1998 in Neurology found that women who had taken estrogen performed better on verbal memory tests that those who had not.
Finally, a study of more than 8,000 women who were not taking estrogen by Dr. Kristine Yaffe, an assistant professor of psychiatry, neurology and epidemiology at the University of California in San Francisco, also suggested a link between natural estrogen levels and cognitive function. Published last year, the study showed that women with more severe osteoporosis had poorer cognitive function than those with less-severe cases of the bone-thinning disease. Low natural levels of estrogen are known to trigger osteoporosis and may explain the poorer cognitive function as well.
And what of estrogen’s ability to prevent and treat Alzheimer’s disease, as opposed to protecting against normal, age-related memory loss?
An analysis of data pooled from 10 observational studies published in1998 in the Journal of the American Medical Association showed a 29 percent lower risk of Alzheimer’s disease among estrogen users. Other studies suggest as much as a 50 percent Alzheimer’s risk reduction in women who have ever taken estrogen supplements.
For treatment, however, the results are less rosy. One study published last February followed women taking one of two doses of estrogen for one year. All had been diagnosed with mild to moderate Alzheimer’s. Even at the higher dose, estrogen did not slow progression of the disease, a result echoed in two other studies last year. The findings suggest that, once brain damage occurs, estrogen cannot fix it.
“We were all surprised and disappointed about these findings because some of the prior research had suggested estrogen would help,” said Dr. Marilyn Albert, director of the gerontology research unit at Massachusetts General Hospital.
Better data about estrogen’s effect on memory should be available in about four years when results from big studies – with fanciful names like WHIMS and WHISCA – are in.
“Before long,” Albert said, “we will know whether or not estrogen is effective and what doses people should take if it is.”
For now, it’s still a guessing game. But many women are betting that estrogen could help.