Like many Americans sliding into middle age, Kimberly McClain started worrying that her memory was beginning to slip.
"It was little things. I couldn't remember what I had for dinner the night before. I had to check to make sure I'd paid the insurance that month. I'd walk into a room and realize I had no idea why I was there," said the Los Angeles marriage counselor, who is 44.
So McClain started a program designed to help -- a detailed regimen that includes daily memory exercises.
"I'm much clearer now," McClain said. "I have no problem finding my keys. I can tell you what I had for dinner last night. I'm not walking into a room thinking, 'Why did I come in here?' "
McClain is among the increasing number of Americans who are performing mental calisthenics, taking Italian classes, deciphering crossword puzzles and hunting for other ways to try to keep their minds from fading.
A large body of evidence indicates that people who are mentally active throughout their lives are significantly less likely to suffer senility, and a handful of studies have found that mental exercises can boost brain function. Elderly people who go through training to sharpen their wits, for example, score much better on thinking tests for years afterward. The minds of younger people who drill their memories seem to work more efficiently.
But it remains far from clear exactly which of the myriad use-it-or-lose-it methods promoted by researchers, self-help books and health groups protect the brain in the long term, and actually reduce the risk for dementia. So scientists, increasingly employing high-tech brain scans, have launched an incipient wave of research to determine what works and why.
"We're right at the cusp of understanding this," said Sherry Willis of Pennsylvania State University. "Because brain imaging work has become so much more technologically sophisticated, we're now at the point where we literally look inside people's brains to try to understand what's going on."
With the population aging, and the number of cases of Alzheimer's and other forms of dementia rising rapidly, experts say preventing mental deterioration from occurring in the first place will be crucial to minimizing the mounting suffering and costs.
"It's really critical that we find ways to prevent, or at least delay the onset of, cognitive decline," said Neil Buckholtz of the National Institute on Aging. "Once the pathology is established in the brain, it's very difficult to treat. We need better ways to prevent the disease in the first place, which could make a huge difference for the future."
Several large studies are examining antioxidants such as selenium, vitamins C and E and folate, as well as the popular herbal remedy ginkgo biloba. Researchers also remain hopeful that anti-inflammatory painkillers such as Celebrex and the hormone estrogen may prove useful, despite safety concerns. Other researchers are exploring whether cholesterol drugs might protect the brain as well as the heart. It has become increasingly clear that the same strategies that cut the risk for heart attacks and strokes -- eating well, lowering cholesterol and blood pressure, avoiding obesity and diabetes, and exercising regularly -- protect the brain, too.
"We don't have to wait until tomorrow when we have some kind of wonder drug," said Arthur Kramer of the University of Illinois at Urbana-Champaign, who has found that sedentary elderly people who start exercising regularly are sharper and experience growth in crucial brain areas. "Many things that we can do today can engender cognitive vitality and successful aging, and one of them is exercise."
Among the most tantalizing evidence are studies that have given rise to the use-it-or-lose-it theory. Several large projects have found that people who are more educated, have more intellectually challenging jobs and engage in more mentally stimulating activities, such as attending lectures and plays, reading, playing chess and other hobbies, are much less likely to develop Alzheimer's and other forms of dementia.
Scientists suspect that a lifetime of thinking a lot may create a "cognitive reserve" -- a reservoir of brain power that people can draw upon even if they suffer damaging silent strokes or protein deposits that are the hallmarks of Alzheimer's.
"Some people might have brain networks that are more efficient and so have a greater capacity to compensate for disease," said Yaakov Stern of Columbia University, who is using brain scans to try to zero in on the circuits that matter most. "So when they are challenged by disease, those networks continue to operate longer."
But it is also possible that such people are born with brains that lead them to pursue intellectually stimulating lives, and are inherently less prone to dementia. Educated, successful people also tend to have more money and get better medical care.
"There's a lot of things that highly educated people do to take care of themselves," said Jerome Yesavage of Stanford University, who is evaluating the benefits of combining cognitive training exercises with a drug already used to slow the progression of Alzheimer's. "You have to be cautious. We don't want to create false hopes that you can prevent Alzheimer's."
In one of the first major attempts to test whether mental training works, a federally funded study involving more than 2,800 elderly people found that those who received 10 brain-training lessons scored much better on thinking tests, and the effect lasted for at least three years. The training taught strategies aimed at improving reasoning skills, the processing of new information, and memory, such as mnemonic devices for remembering names.
Many researchers suspect, however, that people may benefit most from engaging in a rich diversity of stimulating activities. New experiences may be far more important than repeating the same task over and over. Moreover, it may be key to combine mental stimulation with social interaction, which studies have found also appears highly beneficial. Experts say the task should be enjoyable, because stress and other negative emotions appear harmful.
So scientists have launched a series of pilot studies examining more real-life approaches. In Indiana, one team of researchers is testing whether elderly people who take quilting classes fare better, while another is following groups of elderly people as they participate in an adult version of the Odyssey of the Mind competition originally developed for schoolchildren. Outside Chicago, a husband-and-wife team of researchers is experimenting with acting classes. In Baltimore, Johns Hopkins aging experts are studying whether volunteering as tutors and librarians helps. All report promising, though preliminary, findings.
"It was pretty amazing," said Michelle Carlson of Hopkins, whose team found that elderly volunteers scored much better on problem-solving tests and that their frontal lobes seem to have been reinvigorated. "We observed changes that appeared to show that their brains were functioning more like younger adults'."
But none of the researchers said the findings are strong enough to merit specific recommendations.
"I think we'll get there, but we're not there yet," Carlson said.
Other researchers say that although the evidence may remain inconclusive, it is promising enough for people to start doing the things that look as though they may help.
"It's hard to prove a lot of these things, but I'm convinced there's enough evidence that there is a cause-and-effect relationship," said Gary Small of the University of California at Los Angeles, who developed the "memory prescription" that McClain uses.
The prescription combines a healthful diet with daily exercise, relaxation techniques and memory exercises, such as making a mental note of one piece of a family member's wardrobe each morning. Small tested the approach in a pilot study that included McClain. Not only did those on the prescription score better on memory tests, but brain scans lit up in ways that indicated key areas of their gray matter appeared to be working more efficiently, he said.
"One of the most striking findings was how it affected function in the area of the brain that creates everyday working memory," Small said. "We may not have conclusive proof. But the evidence is strong. And these are all healthy choices for other reasons."
Even if such strategies work, getting large numbers of people to fundamentally alter their daily lives remains daunting, many experts acknowledge.
"We all know how difficult it is for all of us to exercise regularly even though we know we should. Now we're telling people they need to be more mentally active, too: 'Turn off "Wheel of Fortune" ' or 'Do your own taxes.' That's going to be a difficult public health message," said Michael Marsiske of the University of Florida.
Marsiske and other experts note, however, that it has been done before.
"The major way we've reduced the death rate from heart disease is through lifestyle changes: eating better, exercising more, smoking less," said David A. Bennett of Rush University in Chicago. "It would require a lot of people to change the way they live, but there's no reason to think we can't have the same impact on Alzheimer's and other forms of dementia."