It starts with a few forgotten names, missed appointments, and words lost on the tip of your tongue. Is it lack of sleep, our crazy lives, or something more ominous?
Most people experience memory losses as they slip past their mid-30s and beyond. Memory mistakes ignored earlier in life suddenly seem worrisome, particularly for women — or at least women tend to talk about their anxiety more than men.
Researchers have long dismissed these common complaints as "just" signs of aging, and too minor to merit serious study. But scientists — many of them female — are starting to take the phenomenon of middle-age memory loss more seriously. They are focusing their research around menopause, which usually occurs when a woman is in her late 40s or early 50s.
A lot of the new research is reassuring.
Although memory does decline during the early part of menopause, it bounces back later in most women, according to findings from the Seattle Midlife Women's Health Study, which began following 500 women in the early 1990s.
Age-related decline may also be generally slower than previously thought, according to a Swedish review of previous research published last month in the journal Trends in Cognitive Sciences. It found that roughly half of men and women avoid significant mental decline until their 60s, and in about 15 percent, the brain stays well-functioning into their 80s.
Memory loss is so mild for most people in their 40s and 50s that scientists generally have had a hard time even detecting a change. Still, many women report being alarmed by what they perceive as a decline.
"There's something going on, but whatever it is seems to be pretty small for most women," said Dr. Victor Henderson, a professor of neurological sciences at Stanford University.
"That's not to minimize what women are experiencing," he said. "As people get older, memory and cognition do change. In most instances, it's for the worse."
Henderson does have one piece of more encouraging news: Midlife memory loss doesn't seem to predict Alzheimer's disease or other types of dementia later in life.
"I don't see evidence that it's a major problem in terms of portending something ominous," Henderson said.
There is, however, a clear connection between memory and the hormone estrogen, which declines during menopause, said Dr. Pauline Maki, professor of psychiatry and psychology at the University of Illinois at Chicago.
"If we take a woman's ovaries out, her verbal memory [the memory for words and language] will decline. If we replace the estrogen, verbal memory returns to baseline," said Maki, also a board member of the North American Menopause Society.
When transitioning through menopause, the dramatic fluctuations of the hormone's levels in the brain "can impact how estrogen is binding in areas of the brain that help us to remember," she said. Poor sleep and hot flashes can also disturb memory, she added, and stress can affect brain estrogen levels, too.
Many women in their 40s and 50s talk about having to work harder to accomplish the same things they did easily earlier in life, said Dr. Hadine Joffe, director of research at Mass. General's Center for Women's Mental Health.
Dr. Karen J. Carlson, director of Women's Health Associates at Massachusetts General Hospital, a primary care practice, said many of her patients going through menopause complain of feeling fuzzy or foggy. They can't multitask the way they used to. They get more overwhelmed and distracted.
Carlson, also an associate professor of medicine at Harvard Medical School, said the scientific evidence is thin that taking hormones will counteract this fogginess. But "anecdotally, my impression is there are some women treated with estrogen therapy who feel like a light bulb has gone on."
Women who have menopause symptoms like hot flashes along with memory problems should talk to their doctor about taking estrogen, Carlson said. Starting the hormone well past menopause won't prevent memory loss and could be harmful, she warns. Use of the hormone has been linked to a raised risk of heart disease, stroke, and breast cancer.
Another factor that influences memory is depression, which can have such a dramatic impact that for many years researchers blamed it for most midlife complaints about memory loss.
But research confirms an independent role for menopause, according to Miriam T. Weber, an assistant professor in the department of neurology at the University of Rochester.
Weber administered a battery of cognitive and other tests to more than 75 women entering menopause.
Most of the decline among women seems to be related to what's called working or short-term memory, as well as to the ability to pay attention, she said.
"There is something to women's complaints," she said. "It's not just all in their heads. It's not just that they're depressed or stressed out."
Weber and others said evidence from the Seattle Midlife Women’s Health Study suggests that — for about 90 percent of women — memory skills lost early in menopause are recovered a few years later, minus the effects of aging.
"The best data we have say that there might be some small subtle declines in certain areas of cognition that seem to rebound once the transition has completed," Weber said. "But we still don't fully know."
Alzheimer's affects different kinds of memory than what's lost during menopause, Weber said. In Alzheimer's, which is more common in women than men, people are unable to store new memories; for middle-age women, the problem is usually with attention, she said.
Genetics can explain about half the difference between those whose memories fade and those whose don't, said Lars Nyberg, a professor of neuroscience at Umeå University in Sweden, who conducted the new study in Trends in Cognitive Sciences. The rest is determined by lifestyle factors, particularly being engaged in social, physical, and mental activities, he said.
High blood pressure and heart disease — conditions that affect blood flow to the brain —- are also believed to play a major role.
"What's good for the heart is good for the brain," said Dr. Anne Louise Oaklander, a neurologist at Mass. General and an associate professor of neurology at Harvard Medical School. She and others suggested that exercise, a healthy diet, stress reduction, and avoiding cigarettes are all important to preventing memory loss.
Perhaps, Oaklander said, memory loss in middle age is just a stage the brain goes through, like adolescence, and is nothing to worry about.
"What's remarkable is not how many people develop midlife cognitive changes," Oaklander said, "but how most people manage to remain functional for many more decades to come despite the ubiquity of these changes."