Using Precision Medicine to Prevent and Treat Alzheimer’s
Despite massive research efforts and numerous clinical trials, we do not yet have drugs that can slow the progression of Alzheimer’s disease. Dale Bredesen, MD, blames that on a reductionist approach to the disease that doesn’t take into account the many factors that may be contributing to an unhealthy brain, such as insufficient oxygen or nutrients. “Doctors will say, ‘You’re not that bad yet. Come back next year.’ And they’ll do that until it’s too late because they have nothing to offer,” he says.
Bredesen recommends a cognoscopy—to assess cognitive health—every year or two starting at age forty-five. His latest book, The End of Alzheimer’s Program: The First Protocol to Enhance Cognition and Reverse Decline at Any Age, describes the personalized, multipronged measures he wants us to implement sooner rather than later.
(If you’re curious about the protocol after reading this Q&A, there’s additional information on it in our September 2018 interview with Bredesen.)
A Q&A with Dale Bredesen, MD
As the saying goes, “Everybody knows a cancer survivor; nobody knows an Alzheimer’s survivor.” It’s the area of greatest biomedical therapeutic failure. We came to the conclusion, after years of research, that what drives the death of neurons is a multifactorial process. With Alzheimer’s disease, you are insufficient in a network that is critical for neuronal support and what is called neuroplasticity, the brain’s ability to form memories and change with experience. Everybody’s talking about misfolded proteins, reactive oxygen species, and prions. Yes, they’re all part of the problem, but what drives the disease process is an insufficiency in the neurons’ support network.
There’s a supply that’s required for that network. And there’s a demand for that network. And people with Alzheimer’s are too low in the supply in relation to the demand. In some people it has to do with sleep apnea. In some people it has to do with not enough blood getting to the brain or enough energy support for the brain. In some people it’s because they’ve been exposed to toxins. People have focused on this idea that we’re going to get a drug that does one thing, but that’s not the way this works. It’s like if a company’s not doing well, saying that we’re going to replace one person in the company and everything’s going to be fixed. No, you’ve got to change the whole culture. You may have to change dozens of people in your company to change company culture.
There are two fundamental differences between our approach and all others: We do not predetermine a treatment, and it’s not a uniform treatment—it’s a personalized treatment. We identify and target the things that are causing the decline. This is no different from precision medicine for oncology, which has changed the way we think about tumors. Tumors have specific genes that drugs target. This is no different from that.
In one person, we’ll predominantly target leaky gut, plus some insulin resistance, plus P. gingivalis from your mouth (which causes gum disease). And in another person, it’ll be low estrogen, exposure to mold toxins, and vascular disease. They’re completely different, but both people end up with Alzheimer’s because the disease results from insufficient support for neurons. So again, it makes no scientific sense to treat Alzheimer’s with a blind one-size-fits-all treatment. It makes all the sense in the world to go after the factors that are causing the decline. They are different from one person to another, and it’s typically multiple factors.
Other factors that can contribute to the disease include high blood sugar; inflammation; toxic chemicals, including mercury, air pollution, formaldehyde, benzene, and toluene; a poor blood supply to the brain; low blood oxygen; stress; and traumatic brain injuries.
I’d call it a systems approach or a precision medicine approach, but you are right: There has been huge pushback. Faculty colleagues and old friends are angry at me because I’m saying something that is not the party line, but the party line is out of date and makes no sense. If I told you, “We’re going to take one hundred cars that are all having problems, and we’re going to fill each one up with gas, and then we’re going to say that that’s the cure for car problems,” yeah, probably in two or three of the cars, it might work. But in the other ninety-seven or ninety-eight, it’s going to be the oil, or it’s going to be the transmission fluid, or it’s going to be the brake lining.
That’s what’s happening with Alzheimer’s. We’re trying to treat this multifactorial disease with a one-size-fits-all approach and, more importantly, a blind process. In most clinical trials, you predetermine a treatment before you see the patient, and it should be just the opposite. Next month, we’re finishing the first clinical trial in history in which we do the opposite. We evaluate each person from head to toe and look at all the different contributors. And then we target those in a personalized protocol. That is the way of the future.
We published one hundred documented cases in which people had a diagnosis and then were treated and improved. I’m just finishing a book called The First Survivors of Alzheimer’s, in which seven of them wrote their stories. I’ll tell you one of many examples: A woman came in when she was sixty-nine years old with several years’ history of difficulty with memory and executive function, which refers to things like organization. She had been in a clinical trial for one of the pharmaceutical antibodies, and each time she was given the antibody, she would clearly get worse.
After the fourth dose of the antibody, she said, “I just can’t do this. I can’t be in this study.” I then worked with her and her doctor, and she started our protocol. She went from a score of twenty-four on the Montreal Cognitive Assessment test (MoCA)—which indicates mild cognitive impairment or pre-Alzheimer’s—to thirty, a perfect score. She has continued her improvement for more than three years now.
In other people, we’ve seen PET scans go from abnormal to normal. We’ve seen MRIs go from showing hippocampal atrophy (shrinkage) to no hippocampal atrophy. [Editor’s note: Brain shrinkage occurs with Alzheimer’s.] And you see improvements—not every time, but you see improvements in cognition. We’ve shown this with multiple tests that measure cognition: CNS vital signs, which is an online cognitive assessment; MoCA; and SLUMS, the Saint Louis University Mental Status exam.
What we believe is that if you’re trying to help patients, instead of spending $300,000 on nursing homes, take one tenth of that and spend it on avoiding a nursing home. So yes, we look at many different variables, although right now you can get an evaluation that’s pretty complete for around $950. We want to look at your inflammation and what’s causing your inflammation, whether you have insulin resistance, your hemoglobin A1C, your hormones, your nutrients, and your nocturnal oxygenation. We want to know if your urine has mycotoxins in it. We want to know if your blood has various toxins in it.
You can look at your own blood oxygen with your Apple Watch. You can look at your sleep patterns with the Oura ring. People can measure their own ketones, their own glucose, their own blood pressure, their own microbiome, their own apo E gene status. There’s so much you can do to identify risk and support your cognition.
It’s basically diet, exercise, sleep, dealing with stress, brain training, some targeted supplementation, detoxification if needed, and drugs that are appropriate. I’m not against drugs—I prescribed them for years and years as a neurologist—but what’s interesting is that the drugs work much better when they are used as part of an optimal protocol. Bioidentical hormone replacement is something that can be quite helpful.
We use a plant-rich mildly ketogenic diet. Ketosis has been one of the most powerful tools to use against cognitive decline, because ketone bodies provide the brain with an alternative fuel to glucose. Ten years before a diagnosis of Alzheimer’s, PET scans show that people have low glucose utilization in the temporal and parietal lobes of the brain. That is the signature of Alzheimer’s disease.
Twelve to sixteen hours of fasting can be helpful. Regular exercise with both aerobic and strength training will help improve ketosis, insulin sensitivity, blood oxygenation, and blood flow to the brain.
There’s evidence that your blood oxygenation at night correlates with the size of parts of your brain. If you’re sleeping at night with an oxygenation of 88 or 90 percent instead of 98 percent, you may have a smaller brain. You want to get oxygen levels to optimal by dealing with sleep apnea and circulation. There are ways to check your oxygen level at night. One device we recommend is the Beddr SleepTuner, and there are also the Apple Watch and the Fitbit.
For brain training, we recommend Brain HQ because there are data published on it.
And then supplements. Supplements have gotten a terrible name because some companies make ridiculous claims. We’re saying supplements are among the things you can do to optimize your biochemistry. For example, if you’ve got low magnesium, which many people with Alzheimer’s do, then you can take magnesium threonate.
It typically takes three to six months for cognition to improve. The most important thing to point out is that when people improve, they stay improved, and we now have people with eight and a half years of sustained improvement on the program. The first person started in April of 2012, and she is still doing great. She’s gone off the protocol four different times. Each time she went off—once, for example, when she got a viral infection—she started to decline again. When you improve, you keep tweaking and you keep striving to make things better and better.
You can find abnormalities in the spinal fluid and in PET scans twenty years before a diagnosis of Alzheimer’s. So there is a long period where you go from no symptoms to noticing cognitive impairment, which lasts about a decade. And then to mild cognitive impairment, which typically lasts a couple of years, until you get to full-blown Alzheimer’s. Saying someone has Alzheimer’s is like saying someone has widely metastatic cancer. It’s very, very late in the overall process. And that’s again one of the things that’s been wrong: People wait to go to the doctor. And unfortunately, many doctors will say, “You’re not that bad yet. Come back next year.” And they’ll do that until it’s too late because they have nothing to offer.
What we’re doing is more like a Pap smear. Let’s look at people as early as possible and get them going because then you can get very good outcomes.
Everybody who is forty-five or older should be on prevention. You can do this online now easily. At Apollo Health, we just introduced something called PRECODE—prevention of cognitive decline—through which you can get blood tests and access to practitioners.
Dale Bredesen, MD, is a neuroscientist who has carried out research on neurodegenerative diseases for over thirty years. Bredesen received a BS from the California Institute of Technology and an MD from Duke University Medical Center. He was chief resident in neurology at the University of California, San Francisco, where he also carried out research with the Nobel Laureate Stanley Prusiner. Bredesen was a member of the National Advisory Council on Aging of the National Institute on Aging and was the founding president and CEO of the Buck Institute for Research on Aging. He is currently on the faculty in the Department of Molecular and Medical Pharmacology at the University of California, Los Angeles. His latest book is The End of Alzheimer’s Program: The First Protocol to Enhance Cognition and Reverse Decline at Any Age. Bredesen works with Apollo Health to implement the Bredesen protocols.
This article is for informational purposes only. It is not, nor is it intended to be, a substitute for professional medical advice, diagnosis, or treatment and should never be relied upon for specific medical advice. To the extent that this article features the advice of physicians or medical practitioners, the views expressed are the views of the cited expert and do not necessarily represent the views of goop.
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