Diet and the Brain

A diet rich in fruits, vegetables, and whole grains, and low in fats and added sugars, can reduce the risk of heart disease, diabetes, and obesity. Can certain dietary patterns or components also help preserve cognitive function and reduce the risk of Alzheimer's disease?

Epidemiological studies have suggested that consuming foods rich in antioxidants—such as brightly colored fruits and dark green, leafy vegetables—may be one way to preserve cognition. Antioxidants, molecules capable of slowing the oxidation of other molecules, are thought to reduce cell damage throughout the body by counteracting free radicals, highly reactive molecules that are by-products of energy production in all cells. With age, either more free radicals are produced, or they are not cleared away as efficiently. They can accumulate in neurons in the brain, causing loss of function. Dr. Cotman describes this oxidative damage as "something like molecular rust." Free radicals occur throughout the body, but the brain's high metabolic rate and long-lived neurons make it particularly vulnerable. The destructive nature of free radicals in the aging brain is yet another focus of AD research.

A team at Harvard Medical School explored the possible benefits of foods high in antioxidants by analyzing epidemiological data from more than thirteen thousand participants aged seventy and older in the Nurses' Health Study. They found that the women who reported eating the greatest amounts of green leafy vegetables (spinach, kale, and romaine lettuce) and cruciferous vegetables (broccoli, cabbage, brussel sprouts, and cauliflower) experienced a slower rate of cognitive decline than women who said they ate the smallest amounts of these vegetables. The apparent benefits of antioxidants remained high even when the scientists accounted for other factors that might have influenced the results, such as the use of vitamins, physical activity, smoking, alcohol consumption, and educational level. Eating fruit did not appear to be associated with improved cognitive ability. The researchers speculated that the high levels of antioxidants and folate (a nutrient that also appears to be important for proper neural activity and cognitive function) in the green leafy and cruciferous vegetables were responsible.

Other epidemiological studies have looked at the whole diet rather than particular components. Studies of adults in Manhattan, for example, link the "Mediterranean diet"—which includes lots of fruits, vegetables, and bread; low to moderate amounts of dairy, fish, poultry, and red wine; small amounts of red meat; and frequent use of olive oil—with a reduced risk of AD and longer survival of people who already had the disease.

Researchers have turned to animal studies to explore the link between diet and AD more directly. In one study conducted on transgenic mice, scientists have found that curcumin, an ingredient in curry that has strong antioxidant and anti-inflammatory properties, prevented the aggregation of beta-amyloid peptides into oligomers and inhibited the toxic effect of these oligomers. Other teams have found that a diet high in DHA, an omega-3 fatty acid found in fish, also reduced beta-amyloid and plaque levels in the brains of transgenic mice. These results are now being tested in a number of clinical trials that are examining the effects of specific dietary components on cognitive decline and AD.

Dr. Cotman and his collaborators have demonstrated that old dogs are for many reasons an even more useful model for this type of research than transgenic mice. Dogs experience cognitive decline as they age and can be tested with cognitive challenges similar to those used in higher order primates and humans. More importantly, their brains naturally accumulate beta-amyloid plaques that are identical to those in people, and the amount of beta-amyloid deposits correlates with the severity of their cognitive decline.

Dr. Cotman collaborated with a research team at the University of Toronto, headed by Dr. William Milgram, to conduct several studies with aged beagles to determine whether an antioxidant-rich diet would improve the dogs' cognitive function, learning ability, and memory. The research team fed the beagles exactly the same diet for three years. ("Try that in a human," Dr. Cotman said. "Nobody is going to eat the same thing for breakfast, lunch, and dinner for three years, but the dogs were fine with it.") The diet was enriched with antioxidants, vitamins E and C, and fruit and vegetable extracts.

The beagles were divided into four groups. A first group was put on the antioxidant supplement diet. The second group had an enriched environment with novel toys and a cage companion, as well as additional opportunities to exercise, but no dietary changes. The third group had both the antioxidant-enriched diet and the enriched environment. The fourth group was a control, provided with a regular diet and a standard environment.

Over the three years, the dogs were given a series of behavioral tests similar to cognitive tests used in research with humans and primates. Even in the first few months of the study, the team saw short-term improvements on some of the learning tests. "We were shocked," Dr. Cotman told us.

"When we began the study, the beagles were between eight and eleven years of age—late-middle age for a dog. We picked this age because we wanted to see if we could make a difference as they aged. At year one, we gave them a hard learning task. None of the animals could perform it. At year two, we started to see an improvement in the animals that were in the combined enrichment and diet group. By year three, the animals on the combined enrichment and antioxidant diet were able to perform the task, but the others still couldn't do it." (The animals that received the enriched diet alone and the behavior enrichment alone also showed improvement—just not as much as those in the group that received both.)

Dr. Cotman took this to mean that this group had gained function. "They were now performing almost as well as a group of younger animals." The study received a good deal of press coverage, and one publication described the results as: "You can teach an old dog new tricks." Dr. Cotman agreed that "it's what we did. We taught an old dog new tricks."

"I'd like to believe that you could teach an old individual new tricks, as well. I'm trying to practice this myself. For instance, I'm learning how to play tennis, which I didn't really know how to do a couple of years ago. So I'm learning a new trick, so to speak—and I'm doing okay at it."

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Excerpted from THE ALZHEIMER'S PROJECT: MOMENTUM IN SCIENCE, published by Public Affairs, www.publicaffairsbooks.com.

Alzheimer's Disease (AD)

A progressive degenerative disease of the brain that causes impairment of memory and other cognitive abilities.

Amyloid Precursor Protein (APP)

The larger protein from which beta-amyloid is formed.

ApoE Gene

A gene that codes for a protein that carries cholesterol to and within cells; different forms of the ApoE gene are associated with differing risks for late-onset Alzheimer's disease. This gene may be referred to as a risk factor gene or a "susceptibility gene" because one form of the gene, called APOE4, is associated with the risk of developing late onset AD.

Beta-Amyloid

Derived from the amyloid precursor protein and found in plaques, the insoluble deposits outside neurons. May also be called A-beta.

Beta-Amyloid Plaque

A largely insoluble deposit found in the space between nerve cells in the brain. The plaques in Alzheimer's disease are made of beta-amyloid and other molecules, surrounded by non-nerve cells (glia) and damaged axons and dendrites from nearby neurons.

Cognitive Reserve

The brain's ability to operate effectively even when some damage to cells or brain cell communications has occurred.

Dementia

A broad term referring to a decline in cognitive function that interferes with daily life and activities. Alzheimer's disease is one form of dementia.

Functional MRI (fMRI)

An adaptation of an MRI (see magnetic resonance imaging) technique that measures brain activity during a mental task, such as one involving memory, language, or attention.

Hippocampal Formation

A structure in the brain that plays a major role in learning and memory and is involved in converting short-term to long-term memory. Also called the hippocampus.

Inflammation

The process by which the body responds to cellular injury by attempting to eliminate foreign matter and damaged tissue.

Insulin Resistance

A condition in which the pancreas makes enough insulin, but the cells do not respond properly to it; characterizes and precedes type 2 diabetes.

Magnetic Resonance Imaging (MRI)

A diagnostic and research technique that uses magnetic fields to generate a computer image of internal structures in the body.

Mild Cognitive Impairment (MCI)

A condition in which a person has cognitive problems greater than those expected for his or her age. Amnestic MCI includes memory problems, but not the personality or other cognitive problems that characterize AD.

Neurodegenerative Disease

A disease characterized by a progressive decline in the structure and function of brain tissue. These diseases include AD, Parkinson's disease, frontotemporal lobar degeneration, and dementia with Lewy bodies. They are usually more common in older people.

Oligomers

Clusters of a small number of beta-amyloid peptides.

Oxidative Damage

Damage that can occur to cells when they are exposed to too many free radicals.

Pittsburgh Compound B (PiB)

The radioactive tracer compound used during a PET (see Positron Emission Tomography) scan of the brain to show beta-amyloid deposits.

Pittsburgh Compound B (PiB)

The radioactive tracer compound used during a PET (see Positron Emission Tomography) scan of the brain to show beta-amyloid deposits.

Synapse

The tiny gap between nerve cells across which neurotransmitters and nerve signals pass.

Tau

A protein that helps to maintain the structure of microtubules in normal nerve cells. Abnormal tau is a principal component of the paired helical filaments in neurofibrillary tangles.

Tangles

A protein that helps to maintain the structure of microtubules in normal nerve cells. Abnormal tau is a principal component of the paired helical filaments in neurofibrillary tangles.

Memory

Normal Aging

Genetic Risk Factor

Dominant and Recessive Genes

Genes and Proteins

Protein-Misfolding Disease

Cholesterol

Biomarkers

Disease-Modifying Drug

Transgenic Mice

An animal that has had a gene (such as the human APP gene) inserted into its chromosomes for the purpose of research. Mice carrying a mutated human APP gene often develop plaques in their brains as they age.

Pathology

Microglia

Insulin & Insulin Resistance

Susceptibility Gene

A variant in a cell's DNA that does not cause a disease by itself but may increase the chance that a person will develop a disease.

Susceptibility Genes

A variant in a cell's DNA that does not cause a disease by itself but may increase the chance that a person will develop a disease.

Genome-Wide Association Study

Vascular Disease

Genetics

Genetics

Normal Aging