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Dale Bredesen on The Ageless Brain: Summary, Critique and Tidied Transcript
Source: https://www.youtube.com/watch?v=GW4aM4aGTmY Host: Neal K. Shah (CEO of CareYaya, caregiving researcher) Guest: Dr. Dale Bredesen (neurologist, founding CEO of the Buck Institute, author of The Ageless Brain) Length: about 55 minutes
Part 1: Summary
Core thesis
Bredesen argues that Alzheimer’s disease is not a random attack on the brain but a protective response. When the brain is short of support or under threat, it switches from “connection mode” (building and keeping synapses) to “protection mode” (making amyloid and phosphorylated tau, which he describes as antimicrobial, and pulling back on synaptic activity). Removing amyloid with antibodies treats the response, not the cause. The aim should be to find and remove what is driving the switch.
What drives the switch
Three major drivers:
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Reduced energetics: poor blood flow, sleep apnea, low oxygen, mitochondrial dysfunction.
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Inflammation: leaky gut, chronic sinusitis, poor oral microbiome, sepsis, tick-borne illness, metabolic syndrome.
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Toxins: inorganic (mercury, air pollution), organic (formaldehyde, benzene, toluene, microplastics) and biotoxins (mould toxins such as trichothecenes, ochratoxin A, gliotoxin).
Three intermediate drivers:
- Low neurotransmitters (for example acetylcholine).
- Low trophic support (NGF, BDNF, hormones, vitamin D, B12).
- Chronic, unresolved stress.
He also names herpes-family viruses (HSV-1, HHV-6A) as microbes that amyloid and tau may be responding to.
Timeline and stages
- Pathology can begin in the teens or twenties; amyloid and tau typically appear about 20 years before diagnosis.
- Four stages: presymptomatic, subjective cognitive impairment (SCI, lasting about 10 years on average), mild cognitive impairment (MCI, 5 to 10 percent convert to dementia each year), and dementia.
- He calls “mild cognitive impairment” a misleading name, likening it to “mildly metastatic cancer”.
- He recommends evaluation from age 35, and a p-tau217 blood test every five years under 60 and every two years over 60.
Claimed outcomes
- Prevention: no case yet of someone following the protocol who went on to develop dementia.
- SCI: virtually all improve and stay improved, with over a decade of sustained improvement in a published paper.
- MCI: in the recent six-site randomised trial, 90 percent of the treatment arm improved, but four sites did very well and two saw no benefit.
- Dementia: roughly 30 to 40 percent improve.
The protocol
Seven basics:
- A plant-rich, mildly ketogenic diet with metabolic flexibility (aiming for ketones above 1.0 mM BHB at least once a day).
- Exercise: strength, aerobic and HIIT.
- Sleep: at least 7 hours, 90 minutes of REM, 60 minutes of deep sleep, and SpO2 of 94 percent or higher.
- Stress management, tracked through HRV.
- Brain training and stimulation (BrainHQ, photobiomodulation).
- Detox, including toxins stored in bone that are released during the “osteoclastic burst” around menopause.
- Targeted supplements (SPMs, urolithin A, magnesium, vitamin D, omega-3s).
Two specifics:
- Treat chronic infections, especially oral pathogens such as P. gingivalis (oral DNA test, rinses, probiotics, cone-beam CT for hidden abscesses).
- Treat chronic toxicity.
Top three for time-poor caregivers
Test first to find out what is wrong. Then:
- Plant-rich, mildly ketogenic diet.
- Exercise, possibly with oxygen therapy (EWOT) or hyperbaric oxygen.
- Sleep, including screening for sleep apnea (he says about 80 percent of US cases go undiagnosed).
Other points
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Psilocybin: promising but early. It may increase neuroplasticity through the 5-HT2A receptor, and he thinks it is best used once the supply problems have been fixed.
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Crosswords and Sudoku: they help only when the brain has enough support, like weight training in someone who is well fed.
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Red wine: one glass a couple of times a week is acceptable if it relieves stress and doesn’t affect sleep.
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Newly diagnosed: find out the stage, work with a well-trained practitioner, and join a support group.
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One dietary change: remove ultra-processed food and sugar.
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One change to medicine: stop relying on single drugs. Combine anti-amyloid drugs with the protocol, since the protocol improved cognition with little change in biomarkers while the drugs changed biomarkers a lot with little change in cognition.
Part 2: Critique
Strengths
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Multifactorial framing. Treating late-onset Alzheimer’s as a disease with many contributing causes, rather than a single amyloid target, matches a large body of opinion. The Lancet Commission estimates that around 45 percent of dementia risk comes from modifiable factors.
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Sensible core advice. Much of the practical guidance is low-risk and supported by evidence: exercise, managing metabolic health, screening for sleep apnea, cutting ultra-processed food, dental care and managing stress. The FINGER trial supports combined lifestyle approaches for slowing decline.
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Early detection. His emphasis on catching the disease early is sound. The biomarker trajectory work he refers to is real (the Chinese cohort study in NEJM in 2024 showed markers becoming abnormal many years before diagnosis). p-tau217 is a well-validated blood marker.
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Honesty about gaps. He acknowledges non-responders, variation between sites, and uncertainty about psilocybin.
Weaknesses and overstatements
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Unverified trial claims. He says three trials have had “the best outcomes of any published clinical trial”. The earlier evidence consists largely of case series (reports of 10 patients in 2014, then 100, then a small 2022 proof-of-concept study with no control group). The randomised trial (NCT05894954) appears, as far as I could find, to have been released as a preprint in December 2025. The claim needs peer-reviewed, blinded and independently replicated data before it can be taken at face value.
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Internal tension in the numbers. “90 percent improved” sits awkwardly beside “two of six sites got nothing” unless enrolment was very uneven between sites. That needs explaining. The site-to-site variation also means results depend heavily on the practitioner, which makes the protocol hard to scale and hard to test.
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Strong outcome claims rest on anecdote. “No one on prevention has developed dementia” and “virtually 100 percent of SCI reverses” come without denominators, follow-up periods or comparison groups. Many people with SCI never progress anyway, so apparent reversal may simply be the natural course or regression to the mean.
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Anti-amyloid drugs are characterised unfairly. Lecanemab and donanemab were never meant to make patients better. They slowed decline by roughly 27 to 35 percent on primary endpoints over 18 months. Whether that is clinically meaningful, and whether it justifies the risk of brain swelling and bleeding (ARIA), is a fair debate. Saying they “have not made people better” is technically true but misleading.
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Amyloid and tau as antimicrobials. The antimicrobial role of amyloid-beta (the Moir and Tanzi work) is a serious hypothesis with animal and cell data. The same claim for tau is much weaker. Neither is established in human Alzheimer’s.
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Precise sleep targets from wearables. Thresholds of 90 minutes REM, 60 minutes deep sleep and SpO2 of 94 percent are presented as validated cut-offs, but they are not. Consumer wearables also estimate sleep stages poorly. SpO2 dips are worth investigating, but the numbers are heuristics.
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Weak evidence for some interventions. The ketone target, EWOT, detox protocols, mould biotoxin testing and the “osteoclastic burst” toxin idea have little controlled evidence. Release of lead from bone around menopause is documented; applying the same idea broadly to other toxins is speculative. The claim that EWOT lowered biological age by 18 years is a single anecdote.
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Commercial interests go undisclosed. Bredesen is linked to Apollo Health, which runs the ReCODE protocol and practitioner training, and to four books. The host runs a caregiving company. Specific products and services (a p-tau lab, oral rinses, photobiomodulation devices, the training course) are named without any disclosure of relationships.
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Softball format. The host does not challenge any claim, and the “rapid fire” section encourages short soundbites over nuance.
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Minor inaccuracies and loose figures. “Storing more than 2,000 home computers” is not a meaningful measurement. “15 percent of Americans die with Alzheimer’s” is roughly consistent with estimates of about one in three older adults dying with some form of dementia, but it is imprecise.
Bottom line
The practical core (metabolic health, exercise, sleep apnea screening, oral health, early biomarker testing) is reasonable and mostly low-risk. The mechanistic story is interesting but only partly established. The outcome claims, especially the near-100 percent figures, are well ahead of the published evidence. Treat the protocol as a plausible bundle of risk reduction rather than a proven reversal treatment, and be wary of the costly add-ons such as detox, biotoxin testing, EWOT and extensive supplement stacks.
Part 3: Tidied Transcript (condensed)
This version removes filler, false starts and repetition, and condenses answers while keeping the speakers’ points and key phrasings. Names and terms are corrected where the auto-captions garbled them. Timestamps mark the start of each section.
[0:00] Introduction
Neal Shah: Introduces the episode from his own experience of watching family members decline, and the sense that “nothing could be done”. About seven million Americans live with dementia, a number expected to double. He introduces Dr. Dale Bredesen, neurologist, bestselling author and founding CEO of the Buck Institute for Research on Aging. Bredesen’s new book, The Ageless Brain, argues that much of what we call inevitable decline may be influenced by sleep, diet and even dental care.
Dale Bredesen: Thanks for having me.
[1:19] An attack on the brain, or a defence?
Neal Shah: Most people picture Alzheimer’s as an attack on the brain. You describe it as the brain protecting itself. What does that mean?
Dale Bredesen: That’s the paradigm shift under way in neurology. We have treated amyloid and phospho-tau as the damage and tried to remove them with antibodies, which hasn’t improved cognition. After 30 years running a lab and 10 years running an institute, we asked what actually drives the loss of synapses, of which you have about 500 trillion. We have to move from asking what the disease is to asking why it happens.
[2:51] The three major drivers
Dale Bredesen: The three big drivers are:
- Reduced energetics: anything that lowers blood flow or oxygen, such as sleep apnea, or mitochondrial dysfunction.
- Inflammation, especially in the brain: leaky gut, chronic sinusitis, changes in the oral microbiome, sepsis, tick-borne illness, and metabolic syndrome, which causes both poor energetics and inflammation.
- Toxins, in three groups:
- inorganics such as mercury and air pollution
- organics such as formaldehyde, toluene, benzene and, increasingly, microplastics
- biotoxins such as trichothecenes, ochratoxin A and gliotoxin, which are badly under-recognised.
[4:28] The three intermediate drivers
Dale Bredesen: The three intermediate drivers are:
- Low neurotransmitters. Without enough acetylcholine you can’t form the memories you’re trying to make.
- Low trophic support: NGF, BDNF, hormones, vitamin D and B12.
- Stress. I used to dismiss it, but short-term stress that resolves is something we evolved to handle. Chronic, unremitting stress is what raises risk.
Most patients have some combination of these, and that combination is what we treat.
[5:36] Amyloid, tau and herpes
Dale Bredesen: Both hallmarks of Alzheimer’s are antimicrobial. Amyloid-beta is an antimicrobial peptide and phospho-tau an antimicrobial protein. They target particular microbes, with herpes-family viruses such as HSV-1 and HHV-6A high on the list. Removing the pathology doesn’t help while the drivers are still active, though it may help later on. We’ve now run three clinical trials, with the best outcomes of any published Alzheimer’s trial.
[7:20] Why the drugs keep failing
Neal Shah: Caregivers ask why Alzheimer’s drugs keep failing. Is the approach flawed?
Dale Bredesen: Yes. Two books cover this: Doctored by Charles Piller, and How Not to Study a Disease by Karl Herrup. We’ve been barking up the wrong tree. Here’s an analogy: if someone had leprosy and you only removed the granulomas with antibodies, the infection would still be there. Our lab work traced the signalling pathways, which explains why estradiol protects against Alzheimer’s, why vitamin D matters, and why NF-kappa-B-driven inflammation switches on amyloid production.
[9:18] Connection mode versus protection mode
Dale Bredesen: The key finding is a systems-level mode switch, like sleep and wakefulness. When conditions are good (low inflammation, plenty of support, good blood flow, oxygen and mitochondrial function), the brain is in connection mode. When they are bad (poor oral microbiome, sinusitis, leaky gut, poor nutrition, sleep apnea), the brain switches to protection mode. It’s like a student preparing for an exam who suddenly hears that a cousin has died: you can only be in one mode at a time. In protection mode the brain makes amyloid and phospho-tau and scales back synaptic connections, putting its resources into defence. It isn’t trying to hurt you.
[11:38] The window for prevention
Neal Shah: You’ve said there’s a window of about ten years before symptoms when this may be almost entirely preventable. What is that window, what are the warning signs, and what are the simplest steps people can take?
Dale Bredesen: I was taught that nothing could be done, but the reality is the opposite: the range of options grows every month. Alzheimer’s is a complex chronic illness like cancer or type 2 diabetes. Pap smears nearly wiped out deaths from cervical cancer (thanks to Dr. Papanicolaou). Diabetes went from a yes-or-no diagnosis to one that HbA1c, fasting insulin and oral glucose tests can pick up years earlier. Alzheimer’s is going the same way, and the earlier you intervene, the better the chance of success.
[14:18] The randomised trial
Dale Bredesen: We’ve just finished a randomised trial across six US sites. Ninety percent of the treatment arm improved compared with standard care. We’re now trying to understand the other 10 percent, and why some people responded strongly and others only modestly.
[14:53] The four stages
Dale Bredesen: Alzheimer’s used to be thought of as a disease of the very old. In fact, pathology can start in the teens or early twenties. If you take on ten insults a day and clear only five, the damage builds up over time. A Chinese study published about eighteen months ago tracked people through to diagnosis and showed when each biomarker became abnormal. About 15 percent of Americans die with Alzheimer’s. Amyloid and tau appear about 20 years before diagnosis, often in people in their thirties and forties. A Kaiser study found that early-onset cases in people in their thirties and forties have been among the fastest-growing groups year on year.
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Presymptomatic. Detectable through blood tests, PET or spinal taps.
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SCI (subjective cognitive impairment). You notice something is wrong, with names, numbers or directions, but you still score normally on tests. It lasts about ten years on average and is completely reversible. Everyone over 35 should be evaluated and start prevention.
[18:52] Cost and the p-tau217 test
Dale Bredesen: The average American spends more than 100,000 dollars on Alzheimer’s care, and doing the right things can avoid most of that. Anyone can get a p-tau217 blood test. The most sensitive one is from Neurocode, available directly through getabrainscan.com. I’m in my mid-seventies and test every two years; people under 60 can test every five.
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MCI (mild cognitive impairment). Abnormal test scores, but daily activities are still intact. About 5 to 10 percent convert to dementia each year.
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Dementia. Daily activities are affected: getting lost while driving, trouble with finances or hygiene.
[20:32] Why “mild cognitive impairment” misleads
Dale Bredesen: MCI is the third of four stages, so calling it “mild” is like telling someone they only have “mildly metastatic cancer”. Nearly all studies, including ours, enrol people with MCI or early dementia. We want people to come in during the first two stages.
[21:13] Outcomes at each stage
Dale Bredesen:
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Prevention: we have not yet seen a case of someone following the protocol who went on to dementia, across more than 2,000 trained doctors in 10 countries.
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SCI: virtually all improve and stay improved. We’ve published sustained improvement lasting more than a decade.
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MCI: 90 percent improved in the trial, though not all fully.
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Dementia: about 30 to 40 percent improve. It’s the difference between a benign tumour and metastatic cancer, although I’ve had reports such as a woman with a MoCA score of zero who is now interacting with her family again.
[23:02] Four brain networks and why they fail
Dale Bredesen: As we evolved, humans chose nervous-system performance over durability. Each high-performance subnetwork has its own supply and demand, and each fails in a different disease:
- neuroplasticity fails in Alzheimer’s
- motor modulation fails in Parkinson’s
- power amplification, the signal from thought to maximal muscle force, fails in ALS
- fine colour discrimination, where we can tell about a million shades apart, fails in macular degeneration.
In each case we ask why supply is chronically too low and demand too high.
[25:59] The seven basics
Dale Bredesen: Treatment rests on seven basics and two specifics.
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Diet: plant-rich and mildly ketogenic, so you are metabolically flexible between ketones and glucose. My wife, a physician, taught me this.
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Exercise: strength, aerobic and HIIT, which work through complementary mechanisms.
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Sleep: I check four numbers every morning. At least seven hours in total, 90 minutes of REM, 60 minutes of deep sleep, and SpO2 of at least 94 percent. Dipping into the 80s or 70s harms the brain and raises the risk of macular degeneration.
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Stress: track your HRV with an Oura ring, Garmin, Fitbit or similar device.
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Brain training and stimulation: BrainHQ, developed by Mike Merzenich, has strong data behind it, as does photobiomodulation (Vielight, Neuronic and others).
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Detox: I wasn’t taught this in training, but everyone is exposed to toxins, including microplastics, and the body stores them in bone, liver, kidney and brain. During the osteoclastic burst in the late forties and early fifties, around menopause, those toxins are released back into the blood, and some people develop cognitive decline at that point.
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Targeted supplements: SPMs, urolithin A, magnesium, vitamin D and omega-3s, depending on the person. They aren’t a cure, but some people who stopped them after the trial struggled. The goal is to raise supply and lower demand so the brain returns to connection mode.
[30:32] The two specifics: infections and toxins
Dale Bredesen: The first specific is chronic infection, such as sinusitis or P. gingivalis in the mouth. Everyone should get an oral DNA test. Treatment options include rinses (for example StellaLife or Dentalcidin), oral probiotics and regular dental work. In the trial we used cone-beam CT to find hidden abscesses. The second specific is chronic toxicity: identify the toxins and detox.
[31:26] Why the practitioner matters most
Dale Bredesen: This is more like surgery than prescription-pad medicine, and skill matters. Of our six trial sites, four got excellent results and two saw essentially no improvement, because of differences in team expertise. ReCODE 2.0 training is taught by experts including Dr. Neil Nathan (mould toxins, with Dr. Ritchie Shoemaker’s work, tick-borne illness and chemical sensitivity), Dr. Ann Hathaway (bioidentical hormones) and Dr. Cyrus Raji (neuroradiology).
[32:49] Three things for stressed caregivers
Neal Shah: Many caregivers have no time. If they could fix only three things, what should they be?
Dale Bredesen: The training takes about 33 hours, but you can skip straight to the quizzes. The first time a clinician sees someone with Alzheimer’s improve, they’re often shocked. One doctor cried when a physician patient came back improved. Dr. Heather Sandison’s assisted living facility, Marama in San Diego, routinely saw residents improve before it was sold. We’re now working with the Vineyards in Fresno, with excellent six-month data.
[35:14] Test before you intervene
Dale Bredesen: First, find out what’s wrong rather than treating blindly. One blood test shows where you stand (p-tau217, like HbA1c for diabetes). Other labs show why: infections, toxins and so on.
[35:49] Priority one: metabolism
Dale Bredesen: Commit to a plant-rich, mildly ketogenic diet, and check glucose and ketones for a couple of weeks. At the Vineyards, CEO Dennis Bacopoulos had his chefs work with Julie G (Julie Gregory), founder of ApoE4.info. She carries two copies of ApoE4, had symptoms in her forties, and is doing very well in her mid-sixties.
My four books:
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The End of Alzheimer’s: the science and the first patients.
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The End of Alzheimer’s Program: practical detail, co-written with Julie G and my wife, Dr. Aida Lasheen.
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The First Survivors of Alzheimer’s: seven patients’ own stories.
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The Ageless Brain: cognition for everyone. There’s no point living to 99, or to 140 as some hope, if your brain gives out at 66.
The people who do best cognitively get their ketones above 1.0 mM BHB at least once a day. If you’re already thin, cycle in and out of ketosis once or twice a week.
[39:50] Priority two: exercise, plus EWOT
Dale Bredesen: Besides strength and aerobic training, consider exercise with oxygen therapy (EWOT), which combines better blood flow with better oxygenation. Hyperbaric oxygen is more expensive and passive but gives more oxygen, and may be the better choice for vascular disease or traumatic encephalopathy. After using EWOT, Julie’s vascular biological age dropped by about 18 years.
[41:38] Priority three: sleep
Dale Bredesen: About 80 percent of sleep apnea in the US goes undiagnosed. It isn’t only overweight, middle-aged men who snore; many thin young women who don’t snore have it too. Home tests such as WatchPAT make checking easy.
[42:42] Psilocybin
Neal Shah: You recently posted about an American woman who reportedly reversed her Alzheimer’s with psilocybin in Brazil, and governments and pharma companies are showing interest. What’s going on?
Dale Bredesen: It’s early days: one recent case of fairly late-stage disease. Psychedelics act on the 5-HT2A serotonin receptor. Just as depression can be read as the body telling you to change course, this system seems to be about rethinking and rewiring, which increases neuroplasticity, the very thing lost in Alzheimer’s. But you don’t want to push neuroplasticity that the brain can’t support. The best use is likely after the supply problems are fixed, in people who have plateaued. Timothy Leary would be pleased about the grants. As always, show me the data.
[46:57] Rapid fire: crosswords and Sudoku
Neal Shah: Do puzzles protect the brain, or do they offer false comfort?
Dale Bredesen: They help if supply is adequate. They’re like weight training, which does nothing for someone malnourished. Fix the support first and puzzles and BrainHQ will do more.
[48:16] Rapid fire: one glass of red wine
Dale Bredesen: It depends on the person. If it relieves real stress without making you drunk or dependent, one glass a couple of times a week is fine. It carries some small risks, but don’t drink it so late that it disrupts your sleep.
[49:15] Rapid fire: just diagnosed
Dale Bredesen: First, find out the stage: presymptomatic, SCI, MCI or dementia. Then work with a well-trained practitioner and ask to speak to patients they’ve helped. Join a support group; Dean Ornish found support groups improved outcomes in heart disease.
[50:02] Rapid fire: one thing to remove from the diet
Dale Bredesen: Ultra-processed food, along with the simple carbohydrates that come with it. Robert Lustig’s Metabolical explains why. I grew up in the fifties and sixties on sugar and am still relearning, trying to avoid the metabolic syndrome that about 100 million Americans have.
[51:14] Rapid fire: one change to Alzheimer’s care
Dale Bredesen: Stop using single drugs on their own. Hitting a complex network problem in one place is scientifically naive. Drugs are fine as part of an overall protocol, and we’re talking to pharmaceutical companies about this. In our trial, cognition improved a great deal while amyloid and tau barely moved. In the antibody trials, the biomarkers moved a lot while cognition barely did. The two approaches should be combined: improve cognition first, then gradually remove amyloid and tau, because in the long run those proteins also remove synapses.
[53:13] Where to find the book, and close
Neal Shah: Where can people get The Ageless Brain and follow your work?
Dale Bredesen: On Amazon, Barnes and Noble or any bookseller. I’m on Instagram, Facebook and X as Dr. Dale Bredesen, and Apollo Health has a YouTube channel. Look at Neurocode and getabrainscan.com for the key markers. It’s a time of real progress, and we want people to act early so they never have to worry about dementia.
Neal Shah: Thanks, and thank you to everyone listening. Please share the episode.
Sources consulted for the critique
