Eric Goulder, MD, FACC
Heart Talk - June 2019
Can Anti-inflammatory Therapies Prevent Alzheimer’s Disease?
Heart-healthy and Stroke-free Living with Eric A. Goulder, MD, FACC
You’ve probably seen headlines reporting that in 2015, researchers at Pfizer made a startling discovery that the company kept secret from the world. According to the Washington Post, which broke this story, “The company’s blockbuster rheumatoid arthritis therapy Enbrel, a powerful anti-inflammatory drug, appeared to reduce the risk of Alzheimer’s disease by 64 percent.” The finding came from an analysis of more than 250,000 insurance claims.
However, Pfizer decided to not to publish the data or pursue a clinical trial even though a 2018 company document obtained by the Post said, “Enbrel could potentially safely prevent, treat and slow progression of Alzheimer’s.” The report comes amid mounting scientific evidence that systemic inflammation may be a key driver of the memory-robbing disorder that strikes at least 500,000 new patients each year. Here’s a look at the latest science on Alzheimer’s prevention and what you can do to avoid chronic inflammation, which has also been implicated in risk for heart attacks, strokes and many other dangerous diseases:
What did the drug company discover and why did they hide it from the world?
The team of Pfizer researchers analyzed insurance claims (without the patients’ names) filed by people with rheumatoid arthritis (RA) and other inflammatory conditions, then split them into two groups of 127,000 each, one for people with Alzheimer’s disease (AD) and one for those without an AD diagnosis. They then checked which patients in each group had taken Enbrel, a drug that combats inflammation by targeting a protein called TFN-a. The drug costs about $5,500.
In the group without an AD diagnosis, 302 people had taken the drug, versus 110 in the AD group, suggesting that Enbrel users were 64% less likely to develop AD. While the numbers were small, when the researchers analyzed hundreds of thousands of insurance claims from a different database, they found a similar reduction in AD rates in those who took the anti-inflammatory drug. A 2016 study by Harvard and Dartmouth researchers analyzed 8.5 million insurance claims and found a 33% lower rate of AD in patients with RA who took the drug.
None of these analyses prove that Enbrel prevents Alzheimer’s or reduces risk for developing it, just that there is a link a small group of people with RA who take the drug. Conducting a large randomized clinical trial (the gold standard of scientific research) with thousands of people is the only way to rigorously investigate if the signal from the analysis is real, but the trial would cost $80 million. The company told the Post that it deemed the likelihood of a successful trial low because its drug does not penetrate the blood-brain barrier.
A former executive at the company told the Post that even if the drug did turn out to reduce risk for AD in a costly clinical trial, the company “won’t be making any money off it.” Enbrel, which was FDA-approved in 1998 for treatment of RA and psoriasis, has reached the end of its patent life and faces competition from generic versions produced by other companies.
What’s the link between inflammation and Alzheimer’s?
The Harvard and Dartmouth study discussed above found that people with RA (an inflammatory disorder) had a higher rate of AD than those without RA. Many studies have linked inflammatory disorders with higher risk for AD. For example, as we recently reported, a 2016 study found that people with severe periodontal (gum) disease were 70% more likely to develop AD than those with healthy gums, and another 2016 study reported that in people who already had the memory-robbing disorder, cognitive decline progressed six times faster in those with gum disease.
In a 20-year study of more than 12,000 people published in Neurology in March, Johns Hopkins scientists found that people with the highest blood levels of inflammatory markers in midlife had the steeper rate of cognitive decline in old age. The findings “implicated inflammation in memory disorders, namely Alzheimer’s disease,” the study’s lead author, Keenan A. Walker, told AARP Magazine. Participants took standard tests of memory and brain function at the start of the study, six to nine years later, and again at the end of the study. Those with the highest levels of the inflammatory marker C-reactive protein (CRP) had a 12% greater decline in those skills than people with the lowest levels of CRP.
A 2018 paper published in the journal Alzheimer’s Dementia that analyzed evidence from dozens of studies concluded that inflammation may be “a central mechanism in Alzheimer’s.” The authors suggest that cardiovascular disease (CVD) and metabolic disorders, such as insulin resistance (IR) and diabetes, among other conditions, can trigger immune system responses that elevate levels of inflammatory markers in the blood, which then travel throughout the body, including the brain, via the more than 60,000 miles of blood vessels in our body.
What are the best ways to combat inflammation and keep my brain and memory sharp?
Systemic inflammation has been implicated in such a long list of chronic disorders that some researchers call it “the mother of all diseases.” Recently media headlines proclaimed “a new era in heart attack and stroke prevention” after a different anti-inflammatory drug was shown to reduce risk for these events and cancer in the CANTOS clinical trial. The placebo-controlled trial studied the effects of canakinumab in 10,061 heart attack survivors, all of whom had high levels of inflammation. The drug, which costs about $200,000, is not currently approved for treatment of heart disease.
However, there’s nothing new about targeting chronic inflammation to protect heart and brain health. In fact, the BaleDoneen Method has been doing exactly that for more than a decade as a key component of our heart attack and stroke prevention plan! Two recent peer-reviewed studies have shown that our comprehensive, personalized approach effectively detects, halts and even reverses CVD. Other research, including studies by the American Heart Association, shows that the same healthy lifestyle habits that protect heart health also protect the brain.
Here are some science-based tactics to reduce arterial inflammation, which we call “fire.”
• Optimize your oral health. A landmark BaleDoneen study was the first to identify oral bacteria from gum disease as a contributing cause of CVD, the leading killer of men and women, often from strokes or heart attacks. Strokes can also cause vascular dementia, a common form of memory loss with similar symptoms to AD. Gum disease, which affects about half of Americans over age 30, has also been linked to higher risk for diabetes, which in turn is a risk factor for developing AD.
• Get checked for insulin resistance. IR, a chronic inflammatory condition, is the root cause of 70% of heart attacks and almost all cases of type 2 diabetes. Collectively, IR and diabetes affect 115 million Americans, many of whom are undiagnosed, escalating their risk for serious or even fatal complications. High blood sugar causes inflammation, which may explain why people with IR or diabetes are at greatly increased risk for AD. We recommend the two-hour oral glucose tolerance test as the most accurate way to find out if you are diabetic or prediabetic.
• Upgrade your lifestyle. Earlier this year, a study by 24 leading experts identified nine potentially reversible lifestyle risks and suggested that by eliminating them, 35% of dementia cases may be preventable. The recommendations included moving more, maintaining a healthy weight, keeping your blood sugar and blood pressure in check, avoiding all nicotine use and exposure to secondhand smoke, engaging in mentally stimulating activities, remaining socially engaged, and getting treatment if you have hearing loss or depression. The BaleDoneen Method also recommends following a diet based on your DNA, which helps reduce stroke and heart attack risk and may also be beneficially to people at increased genetic risk for AD.
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