Why does one woman’s brain thrive as she ages, while another’s declines?

by Barbara Knox for University of Minnesota:Ruth, a 93-year-old grandmother and World War II veteran, lives alone in the second-floor apartment of a Minneapolis duplex. She walks three miles a day on her treadmill, finishes the crossword puzzle every morning, and volunteers at a nursing home twice a week. She’s a great cook and loves to bake, and she’s not averse to a dry martini before dinner once in a while.Ruth’s childhood friend Laura, also 93, lives in the memory-care unit of a nursing home, hopelessly muddled about days and times, waiting for her own mother — dead some 40 years — to come for a visit. While physically healthy, she’s often anxious, sometimes confused and paranoid, and occasionally delusional.Two friends, raised in the same place, both survive to 93 in good physical health, but one lives alone and thrives while the other needs full-time care. Why? What happened to Laura’s brain as she aged? And why didn’t it happen to Ruth’s?“We know that the variation in women’s brains becomes huge around the age of 65,” says Margaret Mahan, a newly minted National Science Foundation (NSF) fellow and University of Minnesota graduate student studying biomedical informatics and computational biology. “Some have excellent memory, some have mild forgetfulness, others, full-scale memory loss — the difference between forgetting where you put your keys and forgetting where you put your car. But we don’t know why it happens.”Exploring the mysterious recesses of the brain has been the life’s work of Apostolos Georgopoulos, M.D., Ph.D., Regents Professor of Neuroscience at the University and director of the Brain Sciences Center at the Minneapolis Veterans Affairs Health Care System. About two years ago, he decided to peer more closely at what happens in the brain as women age — specifically, he wants to know what healthy aging brains look like.His ambitious study, called the Minnesota Women’s Healthy Brain Aging Project, aims to gather comprehensive assessments of healthy women ages 30 to 100-plus to find answers to some perplexing questions: Why does one woman’s brain lose function after age 65, while another woman’s brain remains quite healthy? And was there a clue hidden in that healthy brain that could have led doctors to know that all would be well 20 or 30 years down the road?“Our ultimate goal with this study is a big one: We want to be able to predict, control, and direct brain health,” says Georgopoulos, who holds the American Legion Brain Sciences Chair.Mahan joined the research team after doing a lab rotation with Georgopoulos last year. “I became extremely interested in this study,” she says, “and the broad impact it could have for so many diseases.” She just began her prestigious NSF fellowship, which will provide three years of support for her involvement in the Women’s Healthy Brain Aging study, and is fascinated by not just studying the brain, but by figuring out how to make sense of the complex data the study generates.“The hope of this study,” she says, elaborating on Georgopoulos’s statement, “is that, someday, we can develop a brain index — kind of like there’s a bone-density index that can warn you if you’re in danger of getting osteoporosis — that we could use in a clinical assessment. If we can start forecasting the state of brain aging, that would be huge.”The Brain Sciences CenterThe Minnesota Women’s Healthy Brain Aging Project — and countless other research studies — would not exist without the Brain Sciences Center, which Georgopoulos calls “unique in the whole country.”According to Georgopoulos, when President Reagan declared the 1980s the Decade of the Brain, the VA’s then-chief of psychiatry, Richard Magraw, M.D., began dreaming of building a research unit that would bridge basic brain science and understanding mental illness or, as Georgopoulos says, “a place where we could develop research to understand the brain in both health and disease.”Magraw appealed to veterans, and a spectacular fundraising effort followed. Spearheaded by the American Legion of Minnesota, the call for support galvanized veterans, who pitched in twenties and fifties by the thousands. In the end, they raised more than $1 million entirely through small donations. The University of Minnesota ponied up another $1 million, and the center was up and running.“Our specific mission here is research,” clarifies Georgopoulos, noting that, while the University of Minnesota considers the Brain Sciences Center a fully affiliated outpost, the center is supported equally by the VA and the University. “We don’t deliver treatments. We use magnetoencephalography [a high-tech tool that measures magnetic fields in the brain] to understand the neural mechanisms of mental illness, of posttraumatic stress disorders seen so often in veterans. It allows us to look, noninvasively, at the workings of the brain.”Vigorous women veteransThe inspiration for the Minnesota Women’s Healthy Brain Aging Project came from Georgopoulos’s wife, Angeliki Georgopoulos, M.D., who served as the medical director for the VA’s Women’s Health Center until 2011.“She saw so many elderly women coming in for checkups,” explains her husband, “and she commented on what wonderful shape so many of them were in.” Pondering that, he realized that, as veterans, all of these women would have extensive medical histories already on file. “But the real questions in my mind,” he says, “were, ‘What makes for such a healthy brain? And what can we learn from these women?’”That approach is what makes the project truly one of a kind; instead of focusing on a particular brain disease or syndrome and trying to dissect it, Georgopoulos’s study is all about health — which, ironically, made it a tough sell.“Federal agencies do not fund research for health,” Georgopoulos says dryly. “However much we talk about health maintenance and preventive medicine, grants are virtually always given to studies that focus on disease. Less than 1 percent of federal money is devoted to healthy aging.”But like the Brain Sciences Center itself, the women’s study gained its financial support through a grassroots effort, this one led by Minnesota women who were excited by the project’s goals (see sidebar).“We absolutely could not have done this without the support of these amazing women,” says Georgopoulos.The testingGeorgopoulos and his team developed a series of tests to evaluate the healthy women enrolled in the study. The plan is to reevaluate the volunteers annually for the rest of their lives, which will allow the researchers to track brain changes over time.The women begin by taking the Montreal Cognitive Assessment, a screening test that requires them to remember and repeat sentences; track number sequences; and identify simple line drawings. Then they do a spontaneous memory test, which asks them to describe a picture or a story. They also give blood, which is screened for apolipoprotein E, or APOE, a gene involved in aging and cognition.But it’s the VA’s imaging capability that really gives the team its most comprehensive data. In five different scans, the researchers measure such things as brain chemistry, white matter integrity, and brain volume and activity for each woman.“Ultimately, we want to start identifying which different descriptors are important in brain aging,” says Mahan, “and how we can use those in forecasting brain aging.”Over time, the researchers will release the project’s findings through primary peer-reviewed publications, but they also plan to set up a website that can track the findings long-term and provide updates on major discoveries.One of Mahan’s NSF grant reviewers declared, “This project has potential to be of immense value broadly to society.”“We know that lifestyle impacts brain health,” says Georgopoulos. “Don’t smoke; control your lipids and diabetes risk through diet. … If you care for those things, you’ll have a healthier process. But with the study of these brains of healthy women, what more can we learn? Hopefully, within the constellation of the brain measurements we take, we will find clues to help us predict the course of brain health.”