Dr. David Perlmutter on the Key to Preventing Alzheimer’s Disease

Recently, the United States Food and Drug Administration (FDA) expedited the approval of two types of drugs aimed at addressing β-amyloid, the sticky protein widely recognized as the cause of Alzheimer’s. However, research suggests that decreasing β-amyloids is not the solution to preventing cognitive decline, said David Perlmutter, MD, FACN, ABIHM, at the Integrative Healthcare Symposium in New York City.

"We’re bombarded with the idea that the amyloid hypothesis of Alzheimer's disease is rock solid,” said Dr. Perlmutter, board-certified neurologist and author of Grain Brain, “despite the fact that some of the seminal work in 2006 was found to be fabricated and that the images used for some of the displays of the proteins were actually Photoshopped.”

In fact, anti- β-amyloid drugs haven’t proven to be particularly effective at slowing cognitive decline. According to Dr. Perlmutter, research has shown that while patients treated with anti- β-amyloid drugs showed less cognitive decline than those who didn't take the medication, they still had significant decline. And at 18 months, when patients often experience a substantial and abrupt decline in cognitive function, Dr. Perlmutter explained that both groups showed similar rates of decline.

In addition, the new drugs have been shown to cause adverse side effects. A box warning says that when administered intravenously every other week, these medications can cause brain bleeding and swelling. "But you know, what's a little brain bleeding and swelling anyway," Dr. Perlmutter said.

According to Dr. Perlmutter, one study observed amyloid-related imaging abnormalities (ARIA) in 12.6 percent of treated patients, which included significant changes to the brain, such as hemorrhages and swelling. Dr. Perlmutter said these side effects and the lack of cognitive improvement lead one to question the benefit-risk ratio.

Physicians are led to believe that β-amyloids are the cause of Alzheimer's disease, and we can only treat it with treatments designed to rid the brain, Dr. Perlmutter explained, but that may not be the case. Historical and recent research suggests that beta-amyloid might have protective roles, such as being an antimicrobial peptide or a response to infections (e.g., herpes simplex virus). “Maybe amyloid is there to help us out,” Dr. Perlmutter said. “Maybe the enemy of my enemy is my friend.”

Emerging data indicates that addressing metabolic health with lifestyle interventions is more effective at preventing cognitive decline and Alzheimer's disease than reducing levels of β-amyloids. According to Dr. Perlmutter, Alzheimer's disease begins decades before symptoms like memory loss become apparent. And the changes occurring in the brain leading to Alzheimer's are primarily metabolic.

“Brain glucose hypometabolism, a dysfunction of the brain's ability to metabolize or utilize glucose that happens potentially decades before the clinical manifestation for memory begins to fail,” he said.

Dr. Perlmutter estimated that shifting towards leveraging metabolic health improvements in individual medical care could prevent up to 70 percent of Alzheimer's cases. “While it's important to pull people out of the river,” he said, “it's far more important to find out why they're falling in the first place."

According to Dr. Perlmutter, lifestyle and dietary factors are essential for preventing Alzheimer's and cognitive decline. These include,

1. Physical Exercise: Dr. Perlmutter stressed that regular physical activity is essential. He said exercise not only boosts general health but also has specific benefits for brain health like brain metabolism and insulin sensitivity, crucial factors in preventing cognitive decline.
2. Dietary Habits: The importance of a healthy diet cannot be overemphasized, explained Dr. Perlmutter. He suggests a diet that controls blood sugar levels and provides ample fiber to nurture the microbiome.
3. Nitric Oxide and Cardiovascular Health: Techniques to enhance nitric oxide production, including engaging in physical activity and consuming nitrate-rich foods, can improve blood flow to the brain and support cognitive function, Perlmutter said.
4. Oral Microbiome: Research indicates a connection between the oral microbiome and overall health, including the brain's health. Dr. Perlmutter said maintaining a balanced oral microbiome through diet and avoiding products that disrupt this balance, like certain mouthwashes, could be crucial in preventing cognitive decline.
5. Social Integration and Purpose: Dr. Perlmutter also mentioned broader lifestyle factors, such as social integration and having a sense of purpose, that could lower Alzheimer's risk. He noted observations from blue zones around the world where strong relationships and a sense of purpose are more prevalent, and people maintain cognitive health into older age.