How to Help Prevent and Treat Alzheimer’s Disease

• The trial will assess biological aging, brain aging and epigenetics — The researchers will use newer blood tests that weren’t available even a few years ago, including phospho-tau 181, phospho-tau 217, A-beta 42 to 40 ratio, glial fibrillary acidic protein (GFAP) and neurofilament light polypeptide (NF-L). “A couple of these are not commercially available yet, so we’re doing these as research, but they will all become commercially available,” Bredesen says.

• Early detection and monitoring without a PET scan — Currently, phospho-tau 181 and A-beta 42 to 40 ratio are commercially available, allowing individuals to get an idea of where they stand without necessarily needing a PET scan.

• Tracking improvements and reversing cognitive decline — According to Bredesen, “More importantly, you can follow it as you improve. Prevention is key, but also reversing cognitive decline, which we were the first to do … We’ve seen it again and again, when you’re doing the right things, when you’re attacking the important drivers of the process, you see [reversal].”

• GFAP (Glial Fibrillary Acidic Protein) test — While nonspecific, this test is a valuable tool for detecting brain changes associated with astrocytosis. Astrocytes respond when there’s a problem in the brain, so it can give you a heads-up that something is afoot up to 10 years before symptoms become apparent. “The good news is if it’s normal, you’re in pretty good shape. So you want to know that going forward,” Bredesen explains.

• Phospho-tau 181 and phospho-tau 217 — These are specific tests for Alzheimer’s changes related to the death of neurons.

• Genetic testing for APOE status — Genetic testing is important to ascertain how many copies of the APOE ε4 gene you might have. “That’s an [important] piece,” Bredesen says. “Everybody should know their APOE status.”

• Hormone and toxin testing — Assessing hormone levels and screening for toxins, including mycotoxins and heavy metals, provide additional insights into factors that may contribute to cognitive decline.

• The flawed logic of targeting tau and beta-amyloid — Bredesen explains:

“This is a little bit like saying, ‘There’s some smoke there. If we just blow away the smoke, then the house is not going to burn down.’ It makes no sense. The key thing to know is that [tau and beta-amyloid] are responses and mediators.”

• Alzheimer’s is caused by multiple upstream contributors — While mitochondrial dysfunction is a well-known factor, many other contributors play a role, including:

• Alzheimer’s is fundamentally a network insufficiency — The brain contains about 500 trillion synapses, and when environmental and metabolic stressors weaken this network, cognitive function begins to decline. As a result, tau and beta-amyloid emerge, not as primary drivers but as mediators that amplify the damage.

• Amyloid is an excellent biomarker but a terrible therapeutic target — Dr. Lee Hood and Dr. Nathan Price, authors of “The Age of Scientific Wellness,” emphasize that while amyloid can indicate disease presence, targeting it therapeutically is ineffective, a conclusion supported by clinical data.

• The failure of Lecanemab and what works better — Bredesen criticizes the FDA’s recommendation to approve Lecanemab. “Lecanemab doesn’t make you better, it doesn’t keep you the same, it slows the decline by 27%. That’s it,” he pointed out.

• Other interventions performed better in clinical trials — These include ketones alone, extra virgin olive oil, combined metabolic activators (such as carnitine and nicotinamide riboside) and protocols targeting energetics and inflammation.

• Bredesen’s protocol shows the best long-term results — He states, “We’ve got people now who have sustained their improvement for more than 10 years. So, it’s sad that this drug has been recommended for approval.”

• Dietary intervention — Bredesen recommends a plant-rich, mildly ketogenic diet, with a good omega-3 to omega-6 ratio, no dairy, no grains and no simple carbs. “That’s the approach that has worked the best,” he says. “We call that KetoFLEX 12/3.”

• My concerns about polyunsaturated fats (PUFs) — In the interview, I counter some of Bredesen’s dietary recommendations, as he still recommends PUFs. I’m convinced all omega-6 PUFs need to be kept low, below 2% or even 1% of daily calories, for optimal health.

I strongly suspect people with dementia need to be even more cautious, as linoleic acid (LA) appears to be the biggest dietary source of all the drivers of Alzheimer’s, including inflammation, oxidative stress, mitochondrial dysfunction and dysfunction in electron transport chain such that you cannot efficiently produce ATP.

I’ve written extensively on the ins and outs of this, so for more information, listen to the interview and/or review “Linoleic Acid — The Most Destructive Ingredient in Your Diet.”

• Reevaluating omega fat intake and extended keto — I’m also not convinced that the omega-3 to omega-6 ratio is as helpful as commonly suggested since you cannot counter the damage caused by omega-6 fats simply by taking more omega-3. On top of that, most omega-3 supplements, primarily fish oil, are worthless because they’re synthetic and rancid to boot, so making sure you’re getting high-quality omega-3 is an essential factor.

Lastly, since this interview, I’ve come to appreciate the importance of carbs for brain health, including simple carbs from whole fruits, and the drawbacks of long-term keto. So, please understand, Bredesen’s dietary recommendations are his own, based on his research, and do not necessarily reflect my own views.

• Exercise — Bredesen is seeing particularly good results with KAATSU (blood flow restriction training) and exercise with oxygen therapy (EWOT).

• Sleep optimization — Sleep apnea is a common problem that unquestionably contributes to cognitive decline, as it reduces oxygen to your brain and raises adrenaline while you’re sleeping.

“Sleep is a huge area in and of itself,” Bredesen says. “Patient zero, the first person we treated back in 2012 who reversed her cognitive decline beautifully, she’s now over a decade in on this, doing great continually. She’s now in her late 70s.

One of her issues was poor sleep and, of course, one of the things that was addressed. Getting at least an hour of deep sleep and at least an hour and a half of REM sleep is very helpful … Poor sleep gives you more amyloid. It’s just a marker, but it’s a marker of things that aren’t so good, and unfortunately, amyloid then gives you poorer sleep.”

• Additional strategies — Other important approaches include stress reduction, brain training, detox and targeted supplementation.

• Oral pathogens can invade the brain — Common infections include P. gingivalis and T. denticola, which work their way into your brain from your oral microbiome, herpes simplex and human betaherpesvirus 6A (HHV-6A).

• Herpes viruses are linked to Alzheimer’s — The entire family of herpes viruses is associated with changes in the brain and neurons. HHV-6A in particular is associated with the brain degeneration seen in Alzheimer’s.

• Chlamydia pneumoniae and tick-borne infections pose a risk — Chlamydia pneumoniae is also highly troublesome, as are all tick-borne infections, including Borrelia, Bartonella, Babesia and Anaplasma.

• Infections overstimulate the innate immune system — All these infections put your innate immune system into overdrive and need to be quenched. As noted by Bredesen, COVID-19 and Alzheimer’s are “both innate immune system mismatches with the adaptive system.”

You’re not clearing the pathogen, so you’ve got this continued onslaught of cytokines. In the case of COVID, you die from the acute cytokine storm, whereas in Alzheimer’s, you die from cytokine drizzle. “It’s a long-term cytokine problem,” Bredesen says.

• Fructose signals the body to store fat and reduce ATP production — When the body metabolizes fructose, it interprets the signal as an energy crisis, prompting fat storage and a decrease in ATP production. According to Bredensen:

“It’s really the long-term research of Rick Johnson. You talk about mitochondrial function, about damage to mitochondria. He’s talking about a change in signal. They’re both important. As he points out, when you get that fructose, your body is literally responding to it saying, ‘Winter is coming. We are going to store fat and we’re going to turn down your ATP by about 15%.’”

• Lower ATP levels contribute to cognitive decline — Since the brain is already energy-intensive, reducing ATP production by 15% can push it into a state of dysfunction, contributing to neurodegeneration and Alzheimer’s disease.

• Fructose metabolism mirrors changes seen in Alzheimer’s disease — Research shows that brain changes caused by excessive fructose consumption parallel those seen in Alzheimer’s patients, making dietary choices an essential factor in neurodegenerative disease prevention.

“Rick put together a whole table looking at all the relationships, changes in PET scans, changes in blood biomarkers. In each of these cases, what happens with fructose is the same thing that happens in Alzheimer’s disease.”

• Avoiding excessive fructose is key to preserving brain energetics — While natural fruit consumption in moderation is not problematic, excessive intake of high-fructose corn syrup and processed sources of fructose disrupts brain metabolism and accelerates cognitive decline.

“So again, it comes back to the crucial nature of the energetics, whether you’re turning them down by taking too much fructose and high-fructose corn syrup, which is not to say you can’t eat some fruit, it just means you don’t want to have massive amounts of fructose.”

• The key to this riddle is the Randle cycle — This cycle basically acts as a metabolic switch. Your primary fuels are fats and carbs, and the Randle cycle determines how your cells decide which one to burn. When your diet is more than 30% to 35% fat, this switch shifts to fat metabolism, so that you’re burning fat in your mitochondria rather than glucose. The glucose instead gets shuttled into glycolysis and any excess goes out into your blood.

• Eating a lot of fruit and a lot of fat at the same time is not a good idea — In essence, fructose by itself is not what’s causing the problem. Rather it’s eating too much fructose in combination with too much fat. If you increase your fresh fruit intake, you also need to lower your fat intake, or else the sugar can’t be used for fuel.

• Individual factors influence carbohydrate tolerance — There are individual variations in metabolic flexibility, toxicity and microbiome that likely contribute to a person’s ability to tolerate increased carbohydrates.

• PUFs may also contribute to metabolic dysfunction — The other point of contention I have is that PUFs also appear to induce torpor (decreased physiological activity marked by a reduced metabolic rate), much like high-fructose corn syrup does. So, I suspect ripe fruit is not going to be a major contributor to dementia.

• Fructose from fruit does not behave like high-fructose corn syrup — In a previous interview with Johnson, he also admitted being surprised that fructose from fruit did not have the same effects as high-fructose corn syrup. Bredesen replies:

“Yes. And it makes perfect sense. The interesting thing to me is we are frugivore (animals that thrive on raw fruits), we are descended from frugivores. The problem we have today, of course, is that our fruit has been bred to have a much higher sugar content. That’s the issue.

But the good news is, it retains the wonderful fiber and, as you pointed out, it doesn’t give you that effect that high-fructose corn syrup and processed foods give you.”

• Methylene blue supports mitochondrial function — It facilitates electron transfer forward in the mitochondria, thereby allowing ATP production to occur, even if the complexes are damaged.

• Raising NAD+ is important for energy production — NAD+ is oxidized, not reduced, so it facilitates the transfer of electrons forward in the electron transport chain. While there are expensive precursors out there, my favorite is plain old niacinamide, which is incredibly inexpensive yet raises NAD+ effectively.

• Research confirmed that niacinamide helps slow brain aging — For general health, I recommend taking 50 milligrams of niacinamide three times a day. Niacinamide also works synergistically with methylene blue.

• Dementia patients have low glutathione levels — Exposure to mycotoxins or other toxins. Glutathione in its reduced form is less effective, as the oxidized form is needed for optimal function.

• How to make the actual glutathione molecule — You need both cysteine and glycine, so one way to boost your glutathione level would be to take glycine and N-acetylcysteine (NAC).

• Two other ways to get more glycine into your diet — Eating “nose to tail,” not including muscle meat, or taking a collagen supplement or gelatin powder increases your glycine intake. “Nose to tail” refers to organ meats and connective tissues, which are rich in collagen. Collagen, in turn, makes up about one-third of the protein in your body, so it’s incredibly important. About 30% of the collagen and gelatin is glycine, so it’s an excellent source.

• Alzheimer’s progresses through four stages — Bredesen explains that Alzheimer’s disease develops gradually, moving through distinct phases:

“When you get Alzheimer’s, you go through four stages. You go through a presymptomatic phase, and you go through subjective cognitive impairment (SCI) that lasts on average 10 years. For these areas, prevention and treatment are pretty much 100% effective. We can prevent, and we can reverse virtually every time people are in SCI.”

• Mild cognitive impairment (MCI) is a late stage of Alzheimer’s — Despite its name, MCI is not mild; it signals significant disease progression.

“MCI is the next. It’s too bad it’s called mild cognitive impairment. It’s like telling someone they have mildly metastatic cancer. It’s a relatively late stage of Alzheimer’s disease. Still, in our trial, we had 84% of those people improve,” said Bredesen.

• Reversal is possible, but harder in later stages — While some dementia patients improve with treatment, success rates decrease as the disease progresses.

“The final stage is dementia. And we still see some people with proof of dementia improve. But the farther you go, the harder it is to get them all the way back. So, we encourage everyone, please come in early.

We’ve had people go from MoCA [Montreal cognitive assessment] scores of 18 to 30, which is fantastic, from demented to normal. We’ve had people go from zero to 9. But we’ve never seen anyone yet be able to go from zero MoCA, which is end-stage Alzheimer’s, to perfect 30 …”

• Even small improvements are life-changing — Bredesen recalls a case where a woman with end-stage Alzheimer’s regained independence, even though full recovery was not possible:

“A guy wrote me a nasty note a couple years ago, saying ‘How dare you tell people that if they’re too far along, they shouldn’t get on this protocol? My wife had a MoCA score of zero. She’s in a nursing home.

We used the protocol that you developed, she only went up a little bit, but her symptoms were so much better.’ She could dress herself, she could speak again, she could engage.”

• The best outcomes occur with early intervention — While later-stage patients still see benefits, starting treatment early offers the greatest chance of full reversal. Bredesen noted:

“So I don’t say there’s a limit, but it is much harder below 16. You can get some dramatic subjective improvements. And again, we’ve seen people go from 15 to 27. So, it does happen, it’s just that it’s harder the longer you wait, which is why we encourage everyone to come early. If everybody would come in in those first two phases — prevention or SCI — dementia would be a rare problem.”