Time After Time: Environmental Influences on the Aging Brain

Elizabeth Grossman

Disclosures

Environ Health Perspect. 2014;122(9):A238-A243. 

In This Article

Protective Factors

There is now substantial research investigating how physical activity and exercise affect brain function. This is also the area of research where it is perhaps the easiest to make direct comparisons between animal experiments and human studies. As Arthur Kramer, director of the University of Illinois Beckman Institute for Advanced Science and Technology, and colleagues have written, "Abundant data suggests that physical activity reduces the risk of various diseases, including those associated with compromised cognition and brain function (e.g., heart disease, stroke, obesity) and, in turn, independence and quality of life."[38]

One focus of Kramer's research is to understand the mechanisms by which exercise protects and restores the brain. He and his colleagues have been studying how physical exercise affects the structure and function of the hippocampus—which plays important roles in memory and in organizing and storing information—and what that means for an individual's memory capacity. "Anything that's aerobic seems to have beneficial effects," Kramer says.

Rodent studies have shown that physical exercise—which is known to increase blood flow to the brain—also appears to increase the generation of new neurons in the hippocampus. This activity furthermore appears to increase synaptic plasticity (which could be described as flexibility and ability to change), angiogenesis (or vascular construction), and levels of neurotrophins (the proteins that regulate nerve cell growth and support neural health).[38]

Of particular interest is learning how physical exercise increases the production of new neurons, and how that may enhance performance of certain memory functions. Functions of interest include what's called "relational binding"—for example, remembering the name of a person you recently met and where you met that person. Physical exercise also appears to enhance "visual pattern separation," which enables you to distinguish and remember different patterns—a process that increases memory accuracy. Both functions involve the dentate gyrus region of the hippocampus, which is especially susceptible to age-related changes.[39]

Some studies have reported a doubled or even tripled ability of the dentate gyrus to generate new neurons in rodents that exercised.[40,41] Growth of new dendritic spines, which are important for learning and memory, appears to be stimulated as physical or aerobic exercise increases the expression of genes associated with regulating the secretion of neurotrophin proteins, particularly brain-derived neurotrophic factor, says Kirk Erickson, principal investigator of the University of Pittsburgh Brain Aging and Cognitive Health Laboratory. One hypothesis for this, he explains, is that because exercise stimulates blood flow, it may also increase available levels of brain-derived neurotrophic factor.

In experiments with mice, aerobic exercise has been associated with improved spatial memory.[38,40] Such activity has also been associated with increased hippocampus size, Erickson explained in a talk at the 2014 annual meeting of the American Association for the Advancement of Science,[42] and "no pharmaceutical treatment has been able to replicate this effect." According to Kramer and Erickson, findings from human studies that examined the effects of brisk walking and other aerobic activity have been consistent with those in animal studies.[43]

Physical exercise may also contribute to increased angiogenesis, and increased blood flow to the hippocampus, in turn, is associated with improved cognitive function.[38,44–46] A study that used magnetic resonance imaging to examine cerebral blood vessels found that highly active elderly adults (those who had engaged in aerobic activity for at least 180 minutes a week for the past 10 consecutive years) had brain blood vessel structures similar to those of younger people.[47] The authors pointed out that it was unclear from this study whether aerobic activity had caused the anatomical difference or whether individuals with "younger" brains had been more likely to be physically active.

"Overall," wrote Kramer and colleagues in a 2013 review of the evidence on exercise and brain plasticity, "converging evidence suggests exercise benefits brain function and cognition across the mammalian lifespan, which may translate into reduced risk for Alzheimer's disease in humans."[38] A phase I/II clinical trial of Parkinson's disease patients by these authors suggested that exercising aerobically even for 45 minutes three times a week may markedly improve brain function.[48]

Another important component of maintaining optimal brain function into old age is what is known as cognitive reserve, the brain's ability to optimize performance and compensate for any brain damage.[49] Research by Yaakov Stern, director of the Cognitive Neuroscience Division at the Columbia University College of Physicians and Surgeons, suggests that "exercise changes the brain itself," Stern says, potentially increasing the size of important brain areas that are responsible for synaptic plasticity and enhancing neurovascular function. But in addition to physical exercise, this research indicates that intellectual and social stimulation can potentially increase brain reserve, or the physical structure of the organ.[50,51] However, the mechanisms by which this happens are not yet understood well enough to design interventions, in part because it's difficult to extrapolate animal findings in this area to human experience.

In studies with human adults, Stern and colleagues are measuring what is called efficiency and capacity, or how hard an individual must work to accomplish a particular cognitive task. They are using magnetic resonance imaging to determine what is happening physically in the brain as individuals think their way through the task.[50,51] These researchers are also examining what happens to the brain when it activates compensatory neural networks to make up for the lack of function in others. Part of this research involves trying to understand why some people have better efficiency and capacity and more effective compensatory networks, and also why some proceed into later life with more robust cognitive reserves.

One question being explored is whether cognitive flexibility (the ability to structure information in different ways that is key to analytic thinking) and brain plasticity are enhanced by the stimulation that comes with formal education. Another is how brain flexibility later in life is influenced by cognitive stimuli and other factors over a lifetime and at particular life stages. In a new study, Stern and colleagues plan to look at the combined effects of physical and cognitive stimulation to see if they have additive or synergistic effects. It is clear the older brain responds positively to cognitive or intellectual stimulation, but it is not yet clear, explains Stern, whether or how particular games, puzzles, or other memory tasks actually build cognitive reserve. There is evidence, however, to suggest that older people who are active socially and intellectually do enjoy better cognitive function.[52–54]

At this point, there may be more research questions than answers, but evidence thus far strongly suggests environmental factors can play an instrumental role in influencing neurological function in older adults. Chemical exposures can produce health effects that set the stage for neurological disease and disorders, while physical and intellectual exercise foster brain flexibility and a healthy cognitive reserve. And although investigators have not yet pinpointed how interventions should be designed to produce maximum benefits, so convinced is Kramer of the positive effects of physical and aerobic exercise on neurological health that he believes exercise can reverse, at least temporarily, some of the negative effects of aging on cognitive and brain health.

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