#251 – AMA #46: Optimizing brain health: Alzheimer’s disease risk factors, APOE, prevention strategies, and more

The bottom line here is the earlier you were diagnosed with type 2 diabetes, the higher your risk of dementia.” —Peter Attia

Read Time 49 minutes

In this “Ask Me Anything” (AMA) episode, Peter goes into depth on the topic of brain health, starting with how Alzheimer’s disease is diagnosed, the significance of blood-based biomarkers in diagnosis, and what the various APOE gene variants mean in terms of a person’s risk of developing Alzheimer’s disease. Next, Peter discusses the various strategies for preventing Alzheimer’s disease and neurodegeneration. He touches briefly on exercise as a potent tool, but focuses more on lesser-known factors that could impact brain health, such as nutrition supplementation, lipid management, brain games, sauna, oral health, hearing loss, and more.

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We discuss:

  • Diagnosing Alzheimer’s disease [2:45];
  • Biomarkers for Alzheimer’s disease, the C2N test, and other tools for diagnosis [7:30];
  • Genetic component of Alzheimer’s disease: genes that confer risk [12:45];
  • Understanding your APOE status and why it’s important to know [17:15];
  • The prevalence of Alzheimer’s disease and other forms of dementia, and who is at higher risk [21:15];
  • Can the risk of Alzheimer’s disease be decreased with behavioral changes? [24:15];
  • Overview of modifiable behaviors that potentially play a role in risk reduction of neurodegeneration [30:15];
  • Things that clearly impact brain health: smoking, alcohol, sleep, head injuries, blood pressure, and more [34:15];
  • How nutrition impacts brain health: common diets, metabolic health, energy balance, and more [46:15];
  • Comparing common diets: data showing the association between the incidence of Alzheimer’s disease and specific diets [59:45];
  • Supplements: EPA and DHA, vitamin D, and B vitamins [1:13:00];
  • Supplements: theracurmin, cocoa flavonols, and magnesium L-threonate [1:25:15];
  • Impact of exercise on brain health, minimum effective dose, and the most important types of exercise [1:33:00];
  • Challenging the mind with brain games—does it impact neurodegeneration? [1:43:00];
  • The data on sauna and brain health [1:49:45];
  • Oral health and its association with brain health [1:52:45];
  • How reducing lipids can improve brain health and prevent neurodegeneration [1:55:30];
  • The potential impact of hearing loss on brain health and neurodegeneration [2:04:30]; and
  • More.


Diagnosing Alzheimer’s disease [2:45]

*Previous podcasts on this topic:

“Anyone who has a brain is at risk for this.” —Richard Isaacson [episode #18]

Diagnosing Alzheimer’s disease [4:45]

  • A lot of what we’re going to talk about today is around Alzheimer’s disease because Alzheimer’s disease is both the most common neurodegenerative disease and the most common cause of dementia
  • Some other causes of dementia:
    • vascular dementia, which would be quite prevalent
    • Lewy body dementia
    • Parkinson’s disease
  • As it pertains to the diagnosis of AD, unfortunately, it’s not a neat and tidy diagnosis the way we would have for breast cancer, for instance
  • For AD, it really starts with a clinical diagnosis made by a neurologist
  • They will assess various symptoms such as:
    • Difficulty remembering events
    • difficulty concentrating
    • planning or problem solving
    • confusion with location
    • temporal confusion (confused about different events over time) 
    • language problems
    • reduction in vocabulary, speech, writing, etc.
  • There may be some sort of mental status exam or neuropsychological tests
  • There will also be some lab tests done to rule out other causes
    • For instance, a patient looks like they have all of the signs and symptoms of Alzheimer’s disease, but you come to find out that they’re profoundly hypothyroid, or they have B12 and B6 deficiencies or things like that
  • The bottom line is this diagnosis really isn’t definitively made until an autopsy
    • That said, there are other biomarkers that are increasing in the sensitivity for this
    • we now have the ability to look at serum, amyloid, and tau, and those can be coupled with the things described above, in addition to things like amyloid PET
  • A really good diagnostician can probably be almost assured that a patient indeed has Alzheimer’s disease based on the presentation


Biomarkers for Alzheimer’s disease, the C2N test, and other tools for diagnosis [7:30]

When you talk about cardiovascular disease, you have ApoE as kind of a biomarker that’s kind of a predictor of risk. Is there anything equivalent to that for Alzheimer’s or neurodegeneration?

  • No, Alzheimer’s is much more complicated in this regard
  • We do have biomarkers like amyloid and tau

{end of show notes preview} 

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  1. Great article! Thank you. You had mentioned gene sequencing for APP, PSEN1, and PSEN2. I was curious if you have any experience with any of the major DTC sequencing providers, such as Dante, Nebula, or Sequencing.com and whether their reports do provide an analysis of those particular genes.


    • Although I believe this quote matches what Peter said in the podcast, did he mean to say “insulin sensitive”?

      “I’m not sure what to make of this. Ithink I’m back at the point of: maintain energy balance, stay insulin resistant. We’ll talk about the lack of clear causality there, but I think the reason I just don’t like talking about this is I don’t really know what to say.”

  2. This is a great AMA; thank you. I’m a sixty-nine year old female and recently had my (pretty much worthless) Medicare yearly checkup. The doctor was barely there, either physically or mentally, with her nurse doing all the info intake chores. When the fifteen-minute time limit was up, I tried asking a question, but the doctor already had one foot out the door. What I found most infuriating and condescending was the doctor’s canned advice to play Sudoku or do crossword puzzles to keep my mind active! I actually like difficult crossword puzzles, but I have never discovered any real-life applications. It’s helpful to know that risk of dementia, particularly Alzheimer’s, can be modified, and I look forward to following-up on the links for this episode. One question: are there any studies regarding intelligence levels (however one measures it, and apart from crossword puzzle skills) and Alzheimer’s? I’m not a genius, but I’m fairly intelligent with a curious mind.

  3. Dr Attia
    I’m a 70 yo retired family physician and have greatly enjoyed your podcasts for myself and my patients. I just had my first cataract surgery and was impressed by how much more I could connect with the world around me.
    The evidence of hearing normalization on dementia is strong. What about cataract and other visual corrections? I would expect both daily functioning and social connection would improve based on my own experience and what I’ve observed in my patients.
    Also what about creative, generative mental activities with physical components such as the playing the piano or singing?

  4. My husband who had been diagnosed with Parkinson’s disease for 2 years at the age of 63 had all his symptoms reversed with Ayurveda medicine from naturalherbscentre. com after undergoing their Parkinson’s natural protocol. God Bless all Parkinson’s Caregivers. Stay Strong, take small moments throughout the day to thank yourself, to love your self, and pray to whatever faith, star, spiritual force you believe in and ask for strength. I can personally vouch for these remedy but you would probably need to decide what works best for you.

  5. Thank you. Great AMA and great coverage of a very wide range of modifiable behaviours. I’d be interested in your perspective on the latest advances in gut microbiome research and if you have seen anything either in respect of inflammatory markers or microbiome composition research that is worthy of note in regard to AD?

  6. Thank you ,,, I am long time listener of Peter’s podcasts. At age 76, the topic of AD is important to me. This has been one of the most informative and interesting podcasts that Peter has uploaddd to his website. gts

  7. Seconding Mark Murdock’s comment above:
    1:18:40 “I’m not sure what to make of this. I think I’m back at the point of: maintain energy balance, stay insulin resistant.” Oops.
    BTW, which test(s) do you prefer to use to monitor a patient’s insulin sensitivity? What do you consider to be the optimal range of those tests?

  8. Re: vitamin D: by repeated testing through OmegaQuant, I’ve determined I have to take an average of 7,000 IUs of D3 per day in order to keep my D level around 50 ng/mL. I use USP certified D3, chew the capsule and take it with 1/2 tsp EVOO. Previously, I was taking 10,000 IUs daily with some tahini, until I found that sesame seeds are high in phytosterols. Switching to EVOO instead has allowed me to maintain 50 ng/mL taking an average of 7,000/day.

  9. Peter,
    My father was diagnosed with prostate cancer at age 79 and underwent surgery and hormone therapy to battle the disease. He beat the cancer, but sadly, due to the many rounds of hormone therapy (lupron) and radiation, he developed MCI. He was once an active ER surgeon (working into his late seventies), but I do think lack of sleep over a lifetime really set him up for MCI. The hormones ultimately started the cascade, but many behaviors (lack of sleep, nutrition, lack of regular cardiovascular exercise) prior to his cancer diagnosis may have contributed to his dementia. Can you talk more about the effects of hormone fluctuations on AD and dementia in general? Also, once the cascade has started, is there anything to do to prevent it from worsening (besides exercise, sleep, and eating right)?


  10. Dr. Attia doesn’t have a strong feeling that Vitamin D plays a role in brain health, by itself, but Vitamin D is frequently found to be low in MS patients and regularly supplemented. Does the connection there show a probability that Vitamin D has a greater impact on brain health than we know?

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