INDIANAPOLIS -- Indiana University School of Medicine researchers have been awarded a $2.5 million National Institutes of Health grant to evaluate the advantages of physical exercise, cognitive exercise or a combination of both on the aging brain.
The initial phase of the five-year project will be to develop a clinical study looking at ways to enhance cognitive abilities in older adults with mild memory loss.
The project will build on the research experience of co-principal investigators Frederick Unverzagt, Ph.D., and Daniel O. Clark, Ph.D., and other researchers in the Indiana Alzheimer Disease Center, IU Center for Aging Research, Regenstrief Institute and IU School of Medicine.
If this phase of the research is successful, the clinical study will be expanded to a multi-center study for people with mild cognitive impairment, which is estimated to affect about 5.4 million people in the United States, or about 22 percent of seniors over 71. About 12 percent of people with mild cognitive impairment each year go on to develop dementia.
"Can we change the time it takes to develop dementia through training? That would be huge," Dr. Unverzagt said.
"In randomized trials, there is good evidence that physical exercise improves cognition and brain structure," Dr. Unverzagt said. "Brain scans show improvements in grey matter density in frontal and temporal lobes of the brain in response to exercise. In our earlier studies at Indiana University, we showed that cognitive training improves cognition quite durably -- even up to 10 years -- following the initial training."
"It has been known for years that aerobic and strengthening exercise can improve physical function in older adults," Dr. Clark said. "It is just over the past few years that it has become apparent that exercise also improves cognitive function. Whether the effect of exercise on cognitive function is additive to the effects of cognitive training is the key question of our study."
The IU researchers will explore the potential advantages of physical and cognitive training and will evaluate participants immediately after training and again at a three-month follow-up.
The behavioral study being developed will enroll 160 older adults with mild memory problems and have four arms: exercise only; cognitive training only; combined exercise and cognitive training; and general instruction on healthy aging. Participants will be exposed to the training in 36 sessions over the course of three months, with enrollment beginning in January.
The main outcome will be to determine whether the training improved cognitive abilities. If the study outcome is positive, the protocol will support a larger study to determine whether the trainings can delay the onset of dementia.
Blood samples at baseline and post-training will provide data for secondary analyses of change in growth factors and chronic inflammation. Exercise has been shown to have positive effects on chronic inflammation, reducing some pro-inflammatory markers and increasing some anti-inflammatory markers. Similarly, exercise is known to stimulate the production of growth factors critical in cell growth and proliferation, which may maximize the effects of cognitive training.
Dr. Unverzagt is a professor in the Department of Psychiatry. His research is focused on epidemiology and clinical assessment of cognitive aging and Alzheimer's disease and other dementias. He is nationally recognized for his research focus on non-pharmacologic interventions to improve cognition. Co-investigator Dr. Clark, associate professor in the Department of Medicine and a research scientist with the IU Center for Aging Research and the Regenstrief Institute, has spent his career developing and evaluating preventive health interventions for elderly populations, with special interest on identification and modification of risk factors for chronic disease and physical impairment.
In an earlier landmark behavioral study, Dr. Unverzagt and his team exposed people with normal cognitive ability, age 65 years or older, to exercises designed to stimulate their memory, reasoning, visual attention/processing or no cognitive exercises at all.
"We wanted to know if the cognitive exercises would make them do better on cognitive and memory tests and whether the cognitive training would transfer positively to daily living skills. If so, how long would the training advantage last? The training required the participants to work with a facilitator for 90 minutes a session for 10 sessions over the course of 10 weeks," Dr. Unverzagt said.
"Immediately after training, there was a large benefit of cognitive training on the specific skill trained," Dr. Unverzagt said. "At the five-year mark post training, trained participants still had improved cognitive abilities, and they also reported having less difficulty doing normal living tasks, such as driving, shopping, taking medications. At the 10-year follow-up, gains from that simple early exposure were still detectable."
Dr. Clark and Dr. Unverzagt are optimistic that the gain from combining cognitive and physical exercise will produce better and longer-lasting results, which could be significant as the nearly 76 million baby boomers transition to senior citizens.
Funding for this research was provided by R01 AG045157, National Institute on Aging, "Cognitive and Aerobic Resilience for the Brain (CARB)."