PHILADELPHIA—“We know from several studies that for the average person the equation for risk of dementia or rapid brain aging is about one third genetic and about two thirds nongenetic, so lifestyle factors are important choices,” said Gary W. Small, MD. Because Dr. Small believes “it’s probably true that prevention strategies will be more feasible than attempting to repair neuronal damage once it occurs,” he examined the scientific literature for evidence of different lifestyle habits that might protect the brain. He categorized his findings into four areas: “mental activity—which would include mental training or mental aerobics; physical activity—primarily aerobic physical conditioning; stress reduction or relaxation exercises; and different dietary choices that appear from epidemiological and nutritional studies to be brain protective.” Based on these categories, Dr. Small then devised a 14-day memory and lifestyle training program designed to “keep your brain and body young.”

The program was published in Dr. Small’s book, The Memory Prescription, and the results of a pilot study detailing the effect of the program on cortical metabolism and subjective memory improvement were presented at the Ninth International Conference on Alzheimer’s Disease and Related Disorders.

CATEGORICAL IMPERATIVE

Dr. Small, Director of the Center on Aging at the University of California, Los Angeles, elaborated on the categories that his program comprises. The effect of mental activity, he said, could be defined in terms of a “use it or lose it” theory. “In several studies, college graduates have a lower risk for getting dementia than nongraduates, and leisure activities involving mental effort—such as crossword puzzles or reading—were associated with a decreased risk for Alzheimer’s disease. We also know that cognitive training can have benefits of up to two years in terms of cognitive performance, and practicing mentally challenging tasks appears to improve brain performance and efficiency.”

Animal studies of physical exercise demonstrated that more active laboratory animals have larger hippocampi and that cardiovascular fitness is associated with thicker cortical tissue, Dr. Small continued. In epidemiologic studies, physically active adults have been found to be less likely to develop Alzheimer’s disease, “and physical conditioning—just walking about a half hour a day—has been found to be associated with frontal lobe functioning improvement,” he said.

“In terms of stress effects on memory ability, chronically stressed laboratory animals have been found to have atrophied hippocampi, and if one injects human volunteers with cortisol, it causes acute impairment in learning and recall,” said Dr. Small.

Also, proneness to stress appears to double the risk for Alzheimer’s disease, and chronic exposure to stress may lead to depression, “which has risk implications for memory loss and impaired concentration,” he noted.

Finally, several components contribute to a healthy brain diet. Chief among these is to avoid being overweight or obese, “which increases the risk for hypertension or diabetes, [which] cause small strokes and memory loss.” Additionally, antioxidants from dietary sources and supplements are associated with better brain health. Diets rich in omega-3 fats and low in animal fats have been associated with better brain health, and consuming low–glycemic index carbohydrates (avoiding instant foods) is associated with a lower risk for type 2 diabetes mellitus and therefore fewer strokes and better memory, Dr. Small said.

PILOT PROGRAM

“Based on these kinds of study results, I put together a two-week program that combined strategies that included these various approaches. It’s a very simple, easy-to-follow program that tells people exactly what to do—it even includes modifications for people with special dietary habits … vegetarians, people who dislike fish, and so forth,” noted Dr. Small.

He and his colleagues recruited 17 volunteers ages 35 to 70 to participate in a pilot study of the program. “We had a broad age range because we know from PET [positron emission tomography] imaging studies and neuropathologic studies that brain aging appears to begin early in adult life,” Dr. Small commented.

The cohort had normal memory abilities without evidence of mild cognitive impairment or dementia as defined by the Mini-Mental State Examination. Nine participants were randomized to a control condition in which they continued their usual lifestyle habits, and eight to the 14-day program. “We gave them the manuscript to the program from The Memory Prescription and we spent about a half hour just explaining it to them and called them after a week to make sure they were following the program,” Dr. Small explained. “It was a very motivated group—we didn’t have to drop out volunteers. When we reviewed their daily notes, it was clear that they had conscientiously followed the program,” he noted.

Subjective memory was assessed using a standardized rating scale called the Memory Functioning Questionnaire, a 64-item series of questions related to memory functioning, rated on a 7-point severity scale. Stress and quality-of-life were measured, and brain functioning was analyzed using PET scans that measured the rate of glucose metabolism in different parts of the brain as reflections of synaptic activity; “a very sensitive measure of brain efficiency or even of early Alzheimer’s disease,” according to Dr. Small.

14 DAYS TO A HEALTHIER BRAIN

Volunteers who went on the healthy lifestyle program “had a significant change in functioning in a key memory center, improved subjective memory scores, lower stress levels, lower blood pressure, and their body weight decreased,” Dr. Small reported.

“On the stress-level questionnaire, there was some improvement in stress in the control group, but there was a more dramatic improvement in the active intervention group—though it wasn’t statistically significant, it was just a trend,” Dr. Small noted. “However, when we looked at the Memory Self-Awareness Factor score of the Memory Functioning Questionnaire—which scores how seriously a person rates forgetting names, faces, where you put things, the thread of a conversation, etc—we did see a significant effect where the control group really had minimal change, but there was a big jump in terms of the subjects noticing some improvement in their memory functioning.”

Body weight was very stable in the control group, Dr. Small said, but “even though they had a higher average body weight, the subjects who went on the program had a 2-pound drop in body weight, and that was significant even in this relatively small sample size.” Systolic blood pressure decreased by 10 mm Hg in the memory prescription group but not in the control group, he noted.

PET PROGRAM

“We saw significant change [on PET imaging] in the left dorsolateral prefrontal cortex,” Dr. Small said. “There was some change in the posterior part of the brain but not as significant as in the left dorsolateral prefrontal cortex, where there was an average decline of 5% in the memory prescription group and no change in the controls. This is an area of the brain that regulates working memory, and it’s also involved in brain circuits that regulate stress and anxiety, so that might be consistent with the stress reduction components of this program,” he remarked. “The decreased activity is consistent with the hypothesis that there is greater cognitive efficiency at so-called mental rest. When we did these scans, people were just quiet in the room with dim light and we did not have any cognitive task, so it tells us that working memory might be more efficient even when there’s not a specific task—and the fact that it was in the left hemisphere was consistent with the memory training program which emphasized verbal memory,” he added.

“In conclusion, a 14-day program combining mental conditioning, stress reduction, and healthy diet leads to greater brain efficiency in a working memory center in the brain, improved memory self-ratings, lower body weight, lower systolic blood pressure,” Dr. Small recapped.

“We’ll determine in future studies whether there will be long-term benefits from this kind of program and how each of these different components of the program impacts each of our outcome measures,” he said.

NR

—Justin Romano

Suggested Reading
Grossberg GT, Corey-Bloom J, Small GW, Tariot PN. Academic highlights: emerging therapeutic strategies in Alzheimer’s disease. J Clin Psychiatry. 2004;65:255-266.
Small GW. The Memory Prescription: Dr. Gary Small’s 14-Day Plan to Keep Your Brain and Body Young. New York: Hyperion Books; 2004.
Wang PN, Yang CL, Lin KN, et al. Weight loss, nutritional status and physical activity in patients with Alzheimer’s disease: a controlled study. J Neurol. 2004;251:314-320.
Zandi PP, Anthony JC, Khachaturian AS, et al. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. Arch Neurol. 2004;61:82-88.

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