Trevor Ponder Human Memory

Adding a moderate, but not high, amount of walnuts to an otherwise healthy diet may help older individuals improve performance on tasks that require motor and behavioral skills, according to an animal model study by Agricultural Research Service (ARS)-funded scientists. Walnuts contain polyphenols and other antioxidants and essential fatty acids.

The study was conducted by researchers at Tufts University in Boston, Mass.

The aging brain undergoes many changes that can result in altered or impaired neuronal functioning. Such disruption can be attributed in part to alterations in “synaptic plasticity,” or the ability of the connections between neurons to change in strength and function, and also by increased oxidative damage to neural tissue. In aged rodents, these impairments are seen as poor performance on age-sensitive tests of balance, coordination, and “spatial” working memory.

For the study, weight-matched, aged rats were randomly assigned to one of four diet groups. For eight weeks, the rats were fed special chow mixes that contained either 2 percent, 6 percent or 9 percent walnuts-or no walnuts-before undergoing motor and memory tests. For comparison, the 6 percent walnut study diet is equivalent to a human eating 1 ounce, or about 7 to 9 walnuts, a day. That counts as both a 2-ounce equivalent from the “meat and beans group” and 2 teaspoons toward a daily allowance of dietary oil, as described at MyPyramid.gov.

The study found that in aged rats, the diets containing 2 percent or 6 percent walnuts were able to improve age-related motor and cognitive shortfalls, while the 9 percent walnut diet impaired reference memory. Walnuts, eaten in moderation, appear to be among other foods containing polyphenols and bioactive substances that exhibit multiple effects on neural tissue, according to the researchers.

Memory and Food memory food

Zinc deficiency was first described in Egyptian and Iranian adolescents more than 30 years ago and continues to be a common health problem for children living in both developing and developed countries. As many as 70 percent of school-aged children in Thailand and 34 percent of Chinese preschool children may be zinc deficient. Zinc deficiency in the United States is much less common, with studies showing that about 6 percent of girls and 10 percent of boys are zinc deficient. Such deficiency is known to impair immune function and to retard growth in children. But its impact on brain function and mental performance has been demonstrated only recently.

Zinc is known to be essential for brain development and function in animals. When mice, rats and primates are deprived of zinc during critical periods of brain development, they exhibit many behavioral deficits, particularly in memory, activity, aggression and socialization. Recent work has shown that even mild zinc deprivation of pre-adolescent monkeys results in deficits in both memory and attention. Severe zinc deprivation of adult animals has also impaired their behavior.

When adult men were treated with an agent that removes zinc from the body, they experienced more mood swings and deficits in visual perception and verbal memory. In a highly controlled, 6-month study at the Grand Forks Human Nutrition Research Center we found that men with low zinc intakes had faster, but less accurate performance on tasks measuring verbal and nonverbal memory. In another controlled study at our Center, we found that restricted zinc intakes caused men to perform more poorly on 9 of 15 cognitive and psychomotor tasks. On the other hand, taking a 30-milligram (mg) supplement of zinc each day improved visual memory in a study done with women.

The early studies of severely and moderately zinc-deficient adolescents in Egypt and Iran found “mental disturbances” and “mental lethargy” among those children. Subsequent studies of mental performance of children at risk of zinc deficiency have yielded inconsistent results. In Canada and Guatemala, young school children given an extra 10 mg of zinc daily had no significant improvement in mental performance. But a study of more than 1,000 school-aged children in China conducted by the our Center had different results. Those supplemented with 20 mg of zinc daily showed more improvement in hand-eye coordination, attention and reasoning than the children given a supplement containing most of the essential vitamins and minerals except zinc and four other minerals known to interfere with its absorption. This was the first intervention study to demonstrate in children a relationship between zinc intake and cognition and psychomotor function.

More recently, scientists found similar effects with zinc supplementation of school-aged Mexican-American children living in southwest Texas. These findings suggest that zinc supplementation most likely improves attention, reasoning and psychomotor function, such as hand-eye coordination. It appears that we are now beginning to uncover the role of zinc for brain function and mental performance of children, and the results of this detective work clearly will have very important implications for the world’s population with suboptimal zinc intakes and others who are at risk for zinc deficiency. This work also is another example of the important work on mineral nutrition and human health and performance being conducted at Grand Forks Human Nutrition Research Center.

Good sources of zinc are: oysters, beef, pork, liver, dried beans and peas, whole grains, fortified cereals, nuts, milk, cocoa and poultry.

Memory and Food memory food, zinc

After undergoing surgery, chemotherapy, and radiation therapy for stage II breast cancer, Lori (who asked to be identified only by her first name) was looking forward to getting back to her normal, busy life as a working mother of two.

This image of the human brain uses colors and shapes to show neurological differences between two people. The blurred front portion of the brain is associated with complex thought. (Image courtesy of Arthur Toga, University of California, Los Angeles)

But within weeks of returning full-time to her job as a city planner, she knew something was wrong. “I couldn’t work, I couldn’t think,” she said. Before, multitasking had been second nature, but now it exhausted her. At home, she found that trying to do things like plan dinner for her family was more than she could cope with.

“My brain feels so heavy and tired…I can feel everything slowing down, getting cloudy,” she said.

Lori has the classic symptoms of chemobrain: cognitive changes associated with cancer or cancer treatment, most often experienced as difficulties with concentration, memory, multi-tasking, and planning ability. These changes usually first become apparent during chemotherapy (hence the name) and, in around 20 percent of survivors, persist well after treatment has ended.

A More Complicated Explanation

Although chemobrain was first identified and named by breast cancer survivors, research now suggests that the same constellation of symptoms also affects survivors of other cancers. Early studies of patients’ cognitive functioning after chemotherapy estimated that the number of survivors with chemotherapy-associated cognitive changes ranged from 17 percent to 75 percent.

When researchers began to measure cancer patients’ cognitive functioning both before and after chemotherapy, however, they were surprised to find that before undergoing chemotherapy, 20 to 30 percent of patients had lower cognitive performance than would be expected based on their age and education. Subsequent studies have consistently shown similar findings.

“This suggests that aspects of cancer biology may influence cognitive functioning, or that there are as-yet-unidentified shared risk factors for mild cognitive changes and the development of cancer,” said Dr. Tim Ahles, who studies chemobrain at Memorial Sloan-Kettering Cancer Center.

“It’s more complicated than chemotherapy,” added Dr. Ahles. “Almost no one who is treated for cancer receives only chemotherapy. Other aspects of treatment may be equally important to understanding changes in cognitive functioning.”

Increased Vulnerability

Evidence from animal and imaging studies suggests, for example, that the drug tamoxifen, widely used to treat hormone-receptor-positive breast cancer, may disrupt cognitive and other brain functions. In addition, some studies have found that hormonal agents such as goserelin and leuprolide may cause adverse cognitive effects in men who have prostate cancer.

Studies using functional magnetic resonance imaging have identified structural brain abnormalities in patients treated with chemotherapy. In a study using positron emission tomography imaging, breast cancer survivors who had received chemotherapy in the previous 5 to 10 years used more of their brains to perform a short-term memory task than control subjects who had never received chemotherapy, a sign that their brains are having to work harder to complete the task.

Findings from a preliminary study by Dr. Ahles and his colleagues at Dartmouth Medical School suggest that a form, or allele, of the APOE gene called ε4, which is associated with increased risk for Alzheimer’s disease, may be a genetic marker for increased vulnerability to chemobrain. In this study of 80 long-term survivors of breast cancer and lymphoma, participants with at least one ε4 allele had significantly lower scores on standard tests of visual memory and spatial ability and a tendency toward lower scores on psychomotor functioning than subjects who did not carry this allele.

Dr. Ahles and his team are currently analyzing the data from a larger study, looking at the role of genetic polymorphisms in the development of cancer-related cognitive changes. They are also investigating the hypothesis that patients whose cells have a reduced ability to repair the DNA damage caused by chemotherapy are at higher risk for chemobrain.

Dr. Patricia Ganz and her colleagues at UCLA’s Jonsson Comprehensive Cancer Center suspect that uncontrolled inflammation may be a cause of chemobrain. “Many of the patients in our breast cancer survivorship program who have cognitive complaints also have fatigue, sleep disturbance, or depression,” she said. “Our hypothesis is that polymorphisms in genes that regulate the immune system render some patients more vulnerable to this constellation of symptoms.”

Many cancer treatments, including surgery, radiation, chemotherapy, and immunotherapy, can increase inflammation, Dr. Ganz added, which may not resolve after treatment ends. “We have found that post-treatment fatigue is associated with specific single nucleotide polymorphisms in genes that code for interleukin-1 and interleukin-6, two cell-signaling molecules associated with both inflammation and cancer-related fatigue,” she explained. “Our research is examining whether disruption in immune regulation is also involved in the development of cognitive complaints.”

Treatment Studies

Research on treatments for chemobrain is still in its very early stages. Dr. Ganz is beginning a pilot study of rehabilitation strategies for affected breast cancer survivors. Some evidence suggests that medications that stimulate the central nervous system may moderate adverse cognitive effects.

Lori has obtained some improvement by taking the stimulant Adderall (dextroamphetamine and amphetamine). She also finds that exercise and getting a good night’s sleep help her feel more clear headed.

The most challenging aspect of chemobrain, she said, is its invisibility. “I look fine, so people think I’m well. But my brain still isn’t well.”

Dr. Julia Rowland, who directs NCI’s Office of Cancer Survivorship, is encouraged that this new body of research is bringing needed attention to and better scientific understanding of the cognitive problems that affect many survivors during and after treatment. “The very real challenges caused by cancer-related difficulties with memory and thinking have been poorly understood and are often dismissed when reported by survivors,” said Dr. Rowland. “Findings from these studies should empower survivors to ask their medical providers what can be done to help them improve their cognitive health, especially after treatment ends.”

Human Brain Memory chemobrain