HOW DIET AFFECTS THE AGING BRAIN
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HOW DIET AFFECTS THE AGING BRAIN
ATLANTA, October 15, 2006 - You are what you eat may be an overused mantra to drive home the importance of a particular diet, but recent research shows it may not be worn out yet. The latest findings based on experiments with lab animals as well as people indicate that even as we age, our dietary choices affect our cognitive fitness, and dietary changes may still lead to improvements for the elderly.
"Recent studies show dramatic effects of diet on brain structure and on learning and memory," says Carl Cotman, PhD, of the University of California, Irvine. "The results are startling and exciting with great translational potential."
Narayan Bhat, PhD, at the Medical University of South Carolina, is following on previous research showing links between high cholesterol levels and risk of developing Alzheimer's disease as well as a role for inflammation in triggering the disease. Bhat and his team Neurosciences Department tested their hypothesis that high cholesterol, resulting from either diet or genetic disposition, would exacerbate the brain's inflammatory response and spur amyloid generation that would, in turn, lead to the neurodegeneration and dementia characteristic of Alzheimer's disease.
In a preliminary study, mice were fed a high cholesterol/high fat diet for two months, then tested on a memory task. Results showed a loss of working memory in association with a significant neuroinflammatory response. Parallel studies with a strain of mice with inherent mildly elevated cholesterol levels revealed impaired memory along with higher levels of neuroinflammatory cells and markers regardless of the type of diet they were on.
These findings provide experimental evidence for the current thinking that high cholesterol levels in the body resulting from dietary and/or genetic factors may contribute to the onset of cognitive decline associated with Alzheimer's disease. Implicit in these findings is a new hope for low-fat diets or, potentially, diets high in polyunsaturated fats as a preventive measure against the risk of developing Alzheimer's disease. In addition, an observed connection between diet-induced neuroinflammatory changes and memory deficit emphasizes the potential therapeutic usefulness of anti-inflammatory treatments against Alzheimer's-like dementia.
It is likely that a dysregulation of cholesterol homeostasis may result in an inflammatory cascade as has been observed in cardiovascular disease, atherosclerosis. Potentially, systemic inflammation may also adversely affect tiny blood vessels in the brain, making them less effective at filtering out harmful compounds. The gathering of immune cells at site of inflammation in the brain could then initiate a cascade of events leading to the build-up of amyloid in the brain and synaptic/cognitive dysfunction.
In addition to avoiding high-cholesterol foods, choosing certain other foods may have a positive effect on cognitive function. There is preliminary support for the theory that compounds present in foods made from soy beans may improve or protect memory and other thinking abilities in young and middle-aged adults. The soy compounds may act like estrogen in the brain, which is known to have a positive effect on learning and memory, and may be the driving force for the positive outcomes seen in previous studies.
It is unknown, however, whether older adults will benefit cognitively from soy-based foods, such as soy milk, tofu, and edamame, because the way we digest food changes as we age and certain medications may interfere with the absorption of nutrients in older people. These factors may interfere with the metabolism and absorption -- and therefore the effectiveness -- of soy compounds in the elderly.
To evaluate the potential benefits of soy in the diet of older adults, Carey Gleason of the University of Wisconsin and the Madison Geriatric Research Education and Clinical Center and colleagues conducted a cognitive evaluation of 30 older men and women (average age, 74) while they recorded how much soy they ate. The results of the team's study showed that subjects with higher blood levels of the soy compounds that mimic estrogen achieved better scores on a test of verbal fluency.
"These preliminary findings suggest that it may be the isoflavones contained in soy that benefit cognition, not merely that soy foods improve cardiovascular health and therefore benefit the brain," says Gleason. "Also important is the evidence from the blood analyses showing that several participants who ate soy had measurable levels of plasma isoflavones. Still, there was no correlation between dietary intake and blood levels of the compounds.
"We'll need to look more closely at factors that can effect how dietary soy compounds are metabolized and absorbed in older adults," she notes.
Other findings provide more evidence for the role of antioxidants -- notably in the form of grapes -- in maintaining and improving cognitive function in middle age and beyond.
Alex Poplawsky, PhD, at Bloomsburg University of Pennsylvania, and his colleagues showed that middle-aged rats given a dietary supplement of grape juice and vitamin C remembered the passage of time better than rats not given this supplement -- an accomplishment analogous to a person being able to remember how long it was since they ate their last meal before they should eat again.
Nine-month-old rats -- equivalent to humans at age 28 -- were allowed to drink grape juice freely for a period of three months. When the rats were 12 months old (analogous to a expected to live to 74 at age 37), the researchers trained them to receive a food reward on a set schedule, which required them to wait 10 seconds before by poking their nose in a hole for the food to be delivered. If they responded before the required 10 seconds they had to wait an additional 10 seconds or more before responding to get a food pellet.
In order to get the most food, then, the hungry rat had to respond after 10 seconds had elapsed between responses - but the quicker the better. After 15 days of training, the team found that the most frequent time interval between hole pokes for rats who had been drinking grape juice was between 10 and 12 seconds, while the rats in the control condition responded most frequently between 6 and 8 seconds. Rats given the grape juice supplement learned to wait the required time period faster, and were more efficient at obtaining rewards than the rats that did not receive the supplement before learning this task.
"These findings show that a diet that contains potent antioxidants like grape juice and vitamin C have a beneficial effect on temporal memory and response inhibition in aging rats," says Poplawsky, "and suggest that such a diet may provide some benefit in reducing declines in memory and the ability to restrain oneself -- as when asked to wait -- associated with aging and neurodegenerative diseases," such as Alzheimer's and Parkinson's diseases.
"A diet rich in antioxidants may be an alternative to drug treatments for age-related changes in cognitive and affective behaviors," he notes.
The brain seems to benefit from grapes in their fermented form -- wine -- as well. Using a mouse model of Alzheimer's disease, researchers in the lab of Giulio Pasinetti, MD, at Mount Sinai School of Medicine, New York, gave the mice cognitive tests at 9 and 14 months of age, while over a period of 11 months the mice drank water supplemented with wine made from Muscadine grapes.
Memory function in the Alzheimer's model mice starts to decline when they are 6 months old; plaques appear in the brain at 9 months and become abundant at 14-15 months, when mice are considered middle aged.
Ongoing studies from Pasinetti's laboratory recently found that moderate consumption of red wine, in the form of Cabernet Sauvignon equivalent to daily wine consumption of a single 5-ounce glass for women and two glasses for men, may attenuate cognitive deterioration in a transgenic mouse model of Alzheimer's disease coincidental with decreased type beta amyloid AD neuropathology. But the latest findings showed that the mice given wine learned their way around a water maze faster and more accurately than those drinking water -- and had learned the task well enough to remember it 40 days later.
Pasinetti cautions that alcohol consumption, even in moderate doses, may carry a number of health risks in the general population, as brain cells may be remarkably responsive to what we drink.
"Clarification of the mechanisms through which moderate red wine consumption may beneficially influence Alzheimer's disease," he notes, "and the eventual discovery of future, alcohol-free wine by-products capable of anti-amyloid beta activities in the brain, will help in the development of lifestyle-based therapeutic strategies for Alzheimer's."