Diet Affects Markers of Alzheimer's Disease

Low-Fat, Low-Glycemic-Index Diets Improve Markers for Alzheimer’s Disease, Study Suggests

Medically Reviewed by Louise Chang, MD on June 13, 2011
From the WebMD Archives

June 13, 2011 -- Diets that are low in saturated fat and rich in carbohydrates that steady blood sugar and insulin can beneficially change levels of substances associated with the development of Alzheimer’s disease, a new study shows. Such diets may also improve some measures of memory.

“Diet can have a very significant impact on some of the pathological markers of Alzheimer’s disease,” says study researcher Suzanne Craft, PhD, associate director of the Geriatric Research and Clinical Education Center at the Veterans Affairs Puget Sound Health Care System in Seattle.

“I think we’re starting to see in epidemiologic studies a connection between diet and brain aging, but I think our study is the first that has really shown, in an experimental fashion, that by creating a very carefully controlled diet you could show these very significant effects,” she says.

If further research bears the findings out, experts say the study may point to a way that people can reduce their risk of developing this kind of dementia, which erodes thinking and memory and alters behavior.

The study compared the effects of two different eating patterns on biomarkers in the spinal fluid of healthy older adults and those who had memory loss consistent with early Alzheimer’s.

Half of study participants ate foods high in saturated fat, like red meat and butter, with high-glycemic-index carbohydrates like french fries and sugar-sweetened sodas.

The other half ate a low-fat diet that also had plenty of low-glycemic-index carbohydrates from whole grains, fruits, vegetables, and beans.

The glycemic index  measures how quickly carbohydrates raise blood sugar. Foods that score over 70 cause rapid spikes in blood sugar and are said to be high-glycemic-index foods. Foods that rank under 55 allow blood sugar to rise more gradually and are low on the glycemic index.

Both groups ate the same amount of protein, and the diets were individually balanced so they did not cause weight loss or weight gain.

Healthy people who ate high-fat, high-glycemic-index diets for one month saw increases in spinal fluid levels of beta-amyloid, a fibrous protein that clogs the brains of people who have Alzheimer’s disease.

Eating a low-fat, low-glycemic-index diet, on the other hand, lowered levels of beta-amyloid in healthy adults and improved other markers of inflammation and damage in both groups.

What’s more, people who were already showing signs of Alzheimer’s appeared to be even more sensitive to the diets. They saw blood levels of total cholesterol rise nearly twice as much as those of healthy adults on a high-fat, high-glycemic-index diet.

For both groups, the low-fat, low-glycemic-index diet also improved delayed visual memory, which is the ability to remember and recognize complex patterns.

The study is published in the Archives of Neurology.

“We are getting closer to the day where we might give someone an anti-Alzheimer's diet prescription, but we are not there yet,” says P. Murali Doraiswamy, MD, professor of psychiatry and head of the division of biological psychiatry at the Duke University Medical Center in Durham, N.C.

Studies in animals that have been bred to develop brain changes similar to the kind that occur in Alzheimer’s show that high-fat diets can accelerate the disease, says Doraiswamy, who was not involved in the research. “This is the first randomized trial to test that in humans at risk for Alzheimer's,” he says.

But he also cautions that with just 49 participants, “the study is too small to draw any firm conclusions.”

But he said it should inspire a larger, longer-term study that could provide more definitive results.

Tracking the Influence of Diet on Alzheimer’s

For the study, researchers recruited 49 older adults. Twenty of the participants were healthy and showed no intellectual or memory declines. Twenty-nine had been diagnosed with mild cognitive impairment, a condition that’s thought to be early-stage Alzheimer’s disease.

None of the participants had histories of major mental illnesses, alcoholism, neurologic disorders, diabetes, liver or kidney disease, COPD, or unstable coronary artery disease. None was taking medications to lower cholesterol.

The average age of adults in the healthy control group was 69. Those with mild cognitive impairment were slightly younger, about 67 years old, on average.

Before the study, participants took a battery of tests designed to test how quickly their brains worked and how well they were able to remember things.

Researchers used blood tests to check insulin, glucose, and cholesterol levels.

Researchers also performed spinal taps to analyze participants’ cerebrospinal fluid -- a clear, colorless liquid that bathes the brain and spinal cord.

They measured beta-amyloid, the hormone insulin, a protein that helps in clearing out beta-amyloid called apolipoprotein E, and F2-isoprotanes, which are markers of oxidative damage caused by free radicals.

Half of each group was then randomly assigned to one of two eating patterns.

On the high-fat diet, participants got 45% of their daily calories from fat, including 25% from saturated fat, about 40% of calories came from high-glycemic-index carbohydrates, and about 20% were protein.

On the low-fat diet, 25% of calories came from fat, with less than 7% from saturated fat, 55% to 60% of calories came from low-glycemic-index carbohydrates, and about 20% from protein.

Study meals were delivered to participants twice each week.

Dietary Changes May be More Helpful for Prevention Than for Treatment

After one month on the diets, researchers repeated the original tests.

In healthy adults, the high-fat diet increased levels of beta-amyloid and other markers of inflammation and damage in the spinal fluid, suggesting that the high amounts of unhealthy fats and wide swings in blood sugar and insulin may be moving the brain toward changes associated with Alzheimer’s.

The low-fat diet, however, decreased those levels of beta-amyloid, insulin, and F2-isoprostanes and increased levels of apolipoprotein E, suggesting a protective effect.

In adults who had already begun to have some memory and brain impairment, however, the results were more complex.

Those on the high-fat diet saw little change in the Alzheimer’s biomarkers.

“That’s possibly because they’ve already got a very pathological process going on,” Craft says, and she thinks her short study wasn’t going to make things much worse.

Those who were on the low-fat diet saw increases in the levels of beta-amyloid in their spinal fluid.

Researchers say other studies that have looked at changes in beta-amyloid as Alzheimer’s disease progresses have observed a tipping point, where levels rise until a critical level is reached and plaques begin to form. When that happens, the disease accelerates, more plaques form in the brain, and levels of beta-amyloid in spinal fluid drop.

They say the rise in beta-amyloid seen in adults with cognitive impairment on the low-fat diet may indicate that the brain is moving away from the tipping point of plaque formation and back toward a healthier, more normal state.

People with early memory loss saw other markers of oxidative damage drop on the low-fat diet, and their scores on some measures of memory improved after the study, though the changes were subtle.

Taken together, researchers say their results show that high-fat, high-sugar diets can have consequences for the brain.

“Exposing your body and your brain to this type of diet over a very long period of time is going to put you on the path to Alzheimer’s disease,” Craft says.

As tantalizing as the results, experts urge caution in the interpretation of the results.

“There are many unknowns here, such as how a person’s genetic makeup influences how their diet affects the brain, so it’s entirely possible that a low-fat diet may just help people with a certain genetic makeup," Doraiswamy says. 

“There are also other dietary factors that have also been found to have possible benefit -- low-calorie diets, curcumin, Mediterranean diets rich in antioxidants, etc. Plus we need studies to see if diet plus exercises make a bigger impact,” he tells WebMD in an email.  “So eventually the field will need to put these different diets to the test to see which is the best and it may turn out that there is no such thing as one diet fits all. We may have to tailor a brain-healthy lifestyle based on person's genetics and individual risks.”

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Bayer-Carter, JL. Archives of Neurology, June 2011.

P. Murali Doraiswamy, MD, professor of psychiatry, head, division of biological psychiatry, Duke University Medical Center, Durham, N.C

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