Focus on Healthy Aging

Charles “Chip” F. Reynolds III is director of the Aging Institute of the University of Pittsburgh and the University of Pittsburgh Medical Center (UPMC) Senior Services. He is also the UPMC Endowed Professor in Geriatric Psychiatry in Pitt’s School of Medicine, a professor of behavioral and community health science in Pitt’s Graduate School of Public Health, and director of Pitt’s Intervention Research Center for Late Life Mood Disorders. Reynolds has become an internationally recognized expert on depression prevention and treatment in older adults.

Forty years ago, a 65-year-old American had only a 14 percent chance of reaching the age of 90. Today, thanks to healthier lifestyles, better medical treatments, and wide-ranging geriatric research, that person’s chances have doubled to almost 30 percent. And that eye-opening statistic certainly is not lost on Allegheny County, Pa., which includes the City of Pittsburgh. With nearly 205,000 residents above the age of 65, Allegheny County boasts the second-oldest population in the United States.

A healthcare challenge, indeed, for the region—but an absolute boon for the University of Pittsburgh and its collaborative, multidisciplinary teams of geriatric researchers. These teams have worked with the region’s unique demographic population to develop and grow a diverse and world-renowned aging research program at Pitt.

“Given Pittsburgh’s demographic, what we do here matters to the rest of the nation, whether in basic, clinical, social and economic sciences, or in the development of new models of care for older adults and their caregivers,” says Charles “Chip” Reynolds III, director of the Aging Institute of the University of Pittsburgh and the University of Pittsburgh Medical Center (UPMC) Senior Services and a professor of geriatric psychiatry and behavioral and community health sciences at Pitt. “Pittsburgh will be a microcosm for the rest of the nation in 15 to 20 years. Our opportunity to serve as a pacesetter and innovator in aging science and clinical programs—and in new methods to take them to scale—is second to none.”

The University launched the Aging Institute in 2000 largely to address this burgeoning demographic and the attendant complexity of health-care issues. Since then, the institute has grown in scope and renown and is said to provide one of the nation’s largest and most diverse portfolios of aging-related research and one of the most extensive geriatric and gerontological education programs in the country. In addition, the institute’s multidisciplinary network of comprehensive clinical care is also one of the nation’s largest.

In fiscal year 2010 alone, the University received more than $79 million in aging-related research funding from the National Institutes of Health (NIH) to study cellular aging mechanisms, cell death and recovery, prevention and treatment of balance and mobility disorders, mood disorders, health services research, degenerative diseases such as osteoporosis and Alzheimer’s, and even bioethics.

“The Aging Institute has helped to nurture, link, and leverage research expertise across the University,” says Neil Resnick, Pitt’s Thomas Detre Professor of Medicine and chief of the UPMC Division of Geriatric Medicine and Gerontology, as well as a founder and former director of the Aging Institute.

Even before the institute’s creation, Pitt had begun laying its foundation for aging research with the establishment of two National Institutes of Health (NIH)-funded centers of excellence in aging research: the Alzheimer Disease Research Center and the Intervention Research Center for Late Life Mood Disorders. Other researchers were developing a major research program on sleep, circadian rhythms, and aging. Still others had launched what became known as the Cardiovascular Health Study and the Health, Aging, and Body Composition (Health ABC) Study. To date, thousands of older adults from the Pittsburgh region have participated in those and other ongoing studies.

“These are just a few of the outstanding examples that characterize the longstanding tradition of excellence in NIH-sponsored aging research at Pitt,” says Reynolds, who also is director of Pitt’s Intervention Research Center for Late Life Mood Disorders. “The rich and diverse research base we cultivated throughout the late 1980s and 1990s naturally lent itself to the establishment of a formal Aging Institute.”

Since 2000, institute-affiliated researchers have established at least 21 aging research-related centers of excellence at Pitt, focusing on everything from Alzheimer’s disease, bioethics, chronic disorders, integrative medicine, and epidemiology to geriatric medicine and psychiatry, rehabilitation technology, health-equity research, patient care, and social and urban research. The research programs spinning out of those centers have proven broad and diverse.
A study-rich demographic

Pittsburgh’s aging demographic has served Lewis Kuller and other Pitt researchers well over the years. Kuller, Distinguished University Professor Emeritus of Epidemiology, is known for his establishment of the Healthy Women’s Study, the first and longest study of women from pre- to post-menopause. He also continues to direct the Pittsburgh site of the multicenter Cardiovascular Health Study (CHS)—which has been at Pitt since 1988 and is following about 6,000 people ages 65 and older until their deaths. For more than 40 years, Kuller has been studying risk factors in people with heart disease and diabetes and in menopausal women, as well as investigating the prevention of cancer and cancer’s risk factors.

Kuller also has championed the use of noninvasive technologies to predict, for instance, the prevalence of disease in populations over time. He was among the first to use bone density measurements to study osteoporosis; carotid artery ultrasound to measure vascular disease risk; and brain imaging to explore dementia epidemiology.

Aging’s new challenge: longer lives, but shorter memories

Kuller says that some of his most recent research suggests that the landscape of aging and disease has begun to change rapidly because of healthier lifestyles. But that raises “an interesting new problem now,” he says. “We have gotten so good at treating and preventing cardiovascular disease that we now have a generation of people living into their 80s and 90s, and the most worrisome thing to them is losing cognitive ability. Loss of physical function may be depressing and unpleasant, but there is nothing worse than finding out that you can’t remember or can’t understand something someone said.”

Such findings have motivated Kuller to delve more deeply into cognitive research, in collaboration with Oscar Lopez, professor of neurology in Pitt’s School of Medicine and director of Pitt’s Alzheimer Disease Research Center. As part of that endeavor, Kuller over the past 20 years has been leading the CHS Cognition Study, one of the nation’s largest prospective dementia studies, which uses magnetic resonance imaging (MRI) to identify risk factors and brain changes that might predict the onset of dementia long before it manifests itself in patients.

Among the rising research stars emerging from Kuller’s CHS Cognition Study is Cyrus Raji, a newly minted MD/PhD graduate of Pitt’s School of Medicine. In November 2010, at the annual meeting of the Radiological Association of North America, Raji and his colleagues presented findings from the 20-year study, which included 426 elderly adults, linking increased physical activity to greater brain volume and reduced risk for cognitive impairment.

Specifically, cognitively impaired individuals, the study showed, need to walk at least 58 city blocks—approximately five miles—a week to maintain brain volume and significantly reduce their risk for cognitive decline. Healthy adults, the study concluded, should walk at least 72 city blocks—or six miles—a week.

Chester A. Mathis (standing), professor of radiology and director of the PET (positron emission tomography) facility in the Pitt School of Medicine’s Department of Radiology, and William E. Klunk, Pitt professor of psychiatry and codirector of Pitt’s Alzheimer’s Disease Research Center, developed Pittsburgh Compound B, perhaps the most significant diagnostic advance in Alzheimer’s research today. When used with a PET imaging scan, Pittsburgh Compound-B can help doctors spot a type of brain deposit that is a telltale sign of Alzheimer’s. The discovery could lead to earlier diagnosis of the disease and the possible development of prevention strategies. Mathis and Klunk received the 2008 American Academy of Neurology’s Potamkin Prize (known as the “Nobel Prize for Neurology”) for their work on developing Pittsburgh Compound-B.

Alzheimer’s and Pittsburgh Compound-B

Professors William Klunk and Chester Mathis have developed their own way to predict and diagnose the early onset of Alzheimer’s disease: They have pioneered a radioactive imaging agent, which they call Pittsburgh Compound-B, that has gained international attention because it now allows doctors to diagnose Alzheimer’s early in a patient rather than postmortem. Pittsburgh Compound-B helps doctors using a positron-emission tomography imaging scan to spot beta-amyloid deposits in the brain—a telltale sign of Alzheimer’s. The scanning process can be done early in a person’s development of Alzheimer’s and then used to monitor the disease’s progression.

As a result of their efforts, Klunk, a professor of psychiatry in Pitt’s School of Medicine, and Mathis, a professor of radiology in the medical school, earned the American Academy of Neurology’s Potamkin Prize (known as the “Nobel Prize for Neurology”). Meanwhile, GE Healthcare licensed their innovation from the University and has adapted it; the company is currently running Phase III clinical trials of the product.

Aging more gracefully

Since 1996, Anne Newman, a professor and chair in the Pitt Graduate School of Public Health’s Department of Epidemiology, has led another large aging-related study, called the Health ABC Study. It’s a longitudinal investigation of 1,500 older adults nationwide that assesses the relationship between aging-related physical changes and functional decline. Ultimately, her research promotes the benefits of healthy aging, finding that cardiovascular fitness, a healthy body composition, and regular physical activity help maintain a person’s physical and cognitive health and function in old age. So far, she has parlayed her work into more than 300 scientific journal articles on aging health and longevity.

“When we first started doing our work, many older people were not taking care of themselves,” explains Newman, who is a colleague of Kuller. “They didn’t expect to live past 70, so they figured a healthy lifestyle wasn’t worth the effort. This too-late, too-much-trouble attitude was pervasive throughout the older population.”

Newman, of course, challenged those beliefs and the results were transformational. “Our work found that this same group of people stood to gain the most from preventive health services because, contrary to popular belief, older people’s bodies are remarkably responsive,” she says. “Research has shown that even 90-year-olds with severely atrophied muscle mass can improve their strength by 100 percent.”

In a 2010 Journal of Aging and Health article, Newman and her colleagues, including Kuller, published a report on one of their most recent studies, titled “The 10 Keys to Healthy Aging.” The study examined the effectiveness of a comprehensive, low-cost prevention program in improving adherence to preventive health care goals and overall health for older adults. At the end of the 12-month study, Newman says, the participants had achieved significant health improvements, including lower cholesterol levels, improved control of high blood pressure, better blood-glucose control in diabetics, and higher rates of colon cancer screening.

Neil Resnick is Pitt’s Thomas Detre Professor of Medicine and chief of the UPMC Division of Geriatric Medicine and Gerontology, as well as a founder and former director of the Aging Institute. As part of his own aging research, Resnick works to dispel myths, unravel causes, and devise new treatments for incontinence, one of the most common syndromes affecting older adults. In addition, he’s now investigating ways to transform hospital processes to make acute care more effective, efficient, and safer for older adults.

Plasticity and the aging brain

Another professor of epidemiology, Caterina Rosano, has been undertaking her own longitudinal population studies. She uses highly sophisticated neuroimaging methods to better understand the relationship between the aging brain and cognitive and physical function. “There’s something mysterious about older adults,” Rosano muses. “Why do some adults live longer and better, surviving against all odds?”

In a pilot study, which she published in 2010 in the Journal of Gerontology, Rosano reported that seniors older than 70 years who committed to physical activity over a two-year period— defined as walking at least 150 minutes a week—took cognitive tests faster, made fewer errors, and showed higher brain activation on MRI brain scans than those who remained sedentary. However, in another study examining data from the MRI scans and pen-and-pencil tests of 6,000 aging adults, she found that an estimated 20 percent of participants scored poorly on brain MRI scan measures but extremely well on the cognitive tests.

“One-fifth of the people we look at completely escape any sort of prediction, and this is what is fantastic to me,” Rosano says. “These people function and move around very well, but their brain MRIs don’t look good, and we don’t understand why.”

The effects of skeletal health

Also taking a toll on the aging population’s health and quality of life are degenerative bone diseases that can leave sufferers fragile and at greater risk of injury. Jane Cauley, a professor of epidemiology, has spent 25 years studying skeletal health in aging adults and researching ways to prevent fractures in older men and postmenopausal women. Cauley serves as the principal investigator for the Pittsburgh arm of the Study of Osteoporotic Fractures (SOF), a multicenter study funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Since 1986, SOF has followed a cohort of more than 10,000 women ages 65 or older to determine what factors lead to the development of degenerative bone diseases such as osteoporosis that increase the risk of bone fractures. Among SOF’s major findings to date: Although women who experience accelerated bone loss are more likely to sustain debilitating fractures, a subset of older women actually maintains bone mineral density for up to 15 years, suggesting that bone loss is not an inevitable consequence of aging. The National Institute on Aging recently extended SOF for an additional 25 years of follow-up research.

Cauley also leads the Osteoporotic Fractures in Men study in Pittsburgh, a multicenter, observational study of nearly 6,000 men to determine risk factors for osteoporosis, fractures, and prostate cancer in older men. So far, the study, which began in 1999, has determined that risk factors such as smoking, insulin therapy, and even height can affect different bones.

When older people fall

Of course, osteoporosis and other degenerative bone diseases can contribute significantly to other serious problems in older adults—in particular, falling, which can lead to broken bones and long-term debilitation. But as Stephanie Studenski, a professor of geriatric medicine who has built her research career around the issue of falling, notes, this health threat often stems from several issues.

“Falls are a serious problem and a leading cause of accidental death, disability, and institutionalization in older people,” Studenski says. “Most people who fall, though, fall because they have several conditions that affect their ability to stay upright and have good balance.”

Studenski, an expert on mobility, balance disorders, and falls in older adults, serves as director of Pitt’s Claude D. Pepper Center, a National Institute on Aging-funded center of excellence. She currently leads a group of more than 50 researchers from across Pitt’s schools of the health sciences who have similar expertise.

Aging and incontinence

As part of his own aging research, Neil Resnick works to dispel myths, unravel causes, and devise new treatments for one of the most common syndromes affecting older adults—incontinence. Historically, he says, research on incontinence has been focused solely on the lower urinary tract. But after discovering the age- and disease-related changes that occur in the bladder, as well as identifying a previously unknown cause of geriatric incontinence, Resnick says he found that this approach was too narrow.

His research has shown that incontinence results not only from lower urinary tract dysfunction but also from the body’s inability to compensate for it—problems that occur even with relatively normal bladder function. His studies further demonstrate that, contrary to popular belief, incontinence in older adults is not part of normal aging or dementia—and a broad diagnostic and therapeutic approach focused on compensatory mechanisms leads to superior results not just for incontinence, but for other geriatric conditions as well.

Resnick says these findings have helped to inform his work with Medicare and the World Health Organization to devise a now widely applied approach to geriatric incontinence that minimizes the need for invasive testing and highly specialized consultative expertise. That is, Resnick’s team now is exploring the brain’s role in incontinence.

Destigmatizing depression

Recognizing that depression in older adults is an increasingly common problem, particularly among hospitalized patients, Aging Institute Director Reynolds has become an internationally recognized expert on the topic. In short, Reynolds urges older adults and their caregivers to support a less stigmatizing approach to depression.

“We use medications to relieve depression symptoms and psychotherapy to help get and keep people well,” he explains. “Because late-life depression is a chronic, recurring condition, just like hypertension, chronic obstructive pulmonary disease, or diabetes, it’s important that patients and family caregivers take a long-term view. We can’t cure depression, but we can manage it very successfully to the point that people can be symptom-free and stay that way for long periods of time.”

Among Reynolds’ depression research projects is his team’s study of potential interventions for medically frail older adults at high risk for full-fledged clinical depression. Reynolds and his research team, with support from the University’s Clinical and Translational Science Institute (CTSI), also recently recruited subjects for a study looking at the effectiveness of teaching at-risk older adults problem-solving skills and improved dietary practices to prevent depression.

The preliminary results are so promising, Reynolds says, that the study has been extended further into old age and to underserved minority populations. In fact, the National Institute of Mental Health recently awarded funding to his team to establish a five-year “center of excellence” focusing on late-life depression prevention. Reynolds serves as principal investigator and director of the new center.

Chronic care considerations

Ultimately, age and a host of debilitating health problems do catch up with some older adults, leaving them to suffer for long periods with chronic illness. As such, Resnick has teamed up with Edmund Ricci, a professor of behavioral and community health sciences and associate director of the Aging Institute, to tackle what he considers one of the toughest problems in health care today: caring for the chronically and severely ill older adult. Out of their research has emerged the Acute Care and Transitions Program, an innovative care model designed to focus on a complex systems approach to geriatric care.

“On any given day, hundreds of elderly patients are admitted to UPMC hospitals who are considered to be at high risk for hospital readmission, frequent emergency room visits, or both,” Resnick explains. “Many of these patients have chronic diseases like congestive heart failure or chronic obstructive pulmonary disease that are associated with multiple symptoms—shortness of breath, weakness, palpitations, poor appetite, incontinence, just to name a few. Often these symptoms are not adequately addressed while the patients are in the hospital, and they end up slipping through the cracks at discharge.”

Adds Ricci: “You really need a full baseline assessment [of such aging patients], including caregiver capacity, financial resources, and the home environment. You also need to include the assessments of multiple specialists. As the current system works, it is very difficult to get all of the specialists to communicate, even with the implementation of electronic medical records. Too often, 911 becomes the patient’s default case manager.”

Caregiver Stress

On the other side of the issue of chronic illness are the patients’ personal caregivers, whether spouses or other family or friends, who

Richard Schulz, a Pitt professor of psychiatry and director of the University Center for Social and Urban Research (UCSUR), has been researching the connections between mind and body and between caregiver and patient for more than two decades. Schulz, who also is associate director of the Aging Institute, has earned his place among the nation’s top experts on social behavior and health because of his UCSUR-based research team’s study of the impact of illness and disability in late life on patients and their families.

experience their own quiet suffering. Richard Schulz, professor of psychiatry and director of the University Center for Social and Urban Research (UCSUR), has been researching the connections between mind and body and between caregiver and patient for more than a decade. Schulz, who also is associate director of the Aging Institute, has earned his place among the nation’s top experts on the social behavior and health largely because of his UCSUR-based research team’s study of the impact of illness and disability in late life on people and their partners.

One such study, led by Schulz and published in 2009 in the American Journal of Geriatric Psychiatry, focused on the prevalence and incidence of depression and cardiovascular disease (CVD) in the spouses of people suffering from illness. Among the 1,330 older married couples in the study, husbands whose wives reported high levels of suffering were nearly twice as likely to have CVD and depression as compared to those whose wives did not report suffering.

In another laboratory-based study, Schulz and a team of collaborators from across Pitt’s academic disciplines explored the physiological pathways by which exposure to a loved one’s suffering leads to CVD.

Palliative care and communication

Palliative care, perhaps the most difficult issue along the aging spectrum, often conjures up disturbing thoughts of “giving up,” end-of-life hospice, withdrawal of lifesaving measures, and death, says Robert Arnold, the Leo H. Criep Professor of Patient Care in the Department of Medicine. But he suggests that one of the most pressing shortcomings around such care—and an area in need of improvement—is effective communication.

“Palliative care is about enhancing communication among providers, patients and supporting suffering caregivers and families,” Arnold explains. “Traditionally, palliative care is offered only as an inpatient consult service. However, we are starting to recognize the need to provide palliative care support services in the outpatient setting, too—in nursing homes and communities—so that patients, their caregivers, and their physicians can all be on the same page with respect to understanding what the patients’ goals are, which may be very different from the physicians.”

Arnold, who has focused most of his career on improving the communication skills of physicians dealing with patients’ end-of-life issues, actively trains oncologists and internal medicine physicians across the country to engage more effectively in difficult conversations with patients, such as how to share bad news, explain advance directives, and discuss informed consent.

“The problem is that doctors often learn these communication skills two-thirds of the way through their careers by trial and error,” Arnold says. “We’re trying to develop research projects to see if we can help doctors earlier in their careers learn the skills they need to have these conversations with patients.”

As a result of his recent research efforts, Arnold and a nationwide team of expert faculty researchers have developed what they call the Oncotalk Communication Skills Toolkit, an online toolbox of teaching resources for medical educators teaching ethics and communication. He received funding for the project from the National Cancer Institute.

The politics of aging

Given the fast-growing population of aging adults in the United States, it should come as no surprise that this demographic and its associated health issues have become a serious political target, particularly with regard to health-care reform. As Julie Donohue, a professor in the Pitt Graduate School of Public Health’s Department of Health Policy and Management, can attest, national health-care policy changes can affect medical treatment profoundly for older adults suffering from chronic illnesses. She is conducting research on the effects of recent changes in health-care policy on medication access and spending among older adults with depression and other chronic medical conditions.

In January 2006, for instance, a new drug benefit plan from Medicare, known as Part D, expanded access to beneficiaries who previously had limited or no prescription drug coverage. Donohue’s early studies, she says, indicate that Part D not only has reduced out-of-pocket drug expenditures, but also has increased medication use. However, until recently, no breakdown by clinical condition, such as depression, had been performed.

As part of her study, Donohue says she analyzed medical and pharmacy insurance claims data throughout Western Pennsylvania over a four-year period from more than 30,000 Medicare beneficiaries with a diagnosis of depression. Her outcome measures included the initiation of antidepressant therapy, duration of therapy, and adequate adherence before and after implementation of Part D. Her results, published in the American Journal of Geriatric Psychiatry, found that Medicare Part D was associated with improvement in antidepressant use and adherence by depressed older adults who previously had no or limited drug coverage.

Taken together, the growing aging population, the complexities of aging-related health care, and the politics affecting it, provide ample directive for Pitt researchers to continue to make aging research an internationally recognized academic and clinical priority at the University of Pittsburgh.

“Aging in this country and worldwide is the monumental issue of our generation,” Resnick says. “It is a vast and unprecedented challenge to us all. Together as physicians, scientists, basic researchers, and policymakers, we can devise solutions that none of us could do alone. In fact, imagination is our only limit.”