#101

I consume gallons of olive oil every year so always pleased to see positive research Found this interesting RCT on the benefit of ev olive oil on neuro inflammation and the blood brain barrier. Apologies if this has been posted already.

3 Likes
#102

New video from Dr. Bredesen. He does a really good job focusing on what has worked for Alzheimer’s interventions. A lot of it, he has already discussed, but this one really focused on the importance of Mercury and the oral biome, which both have a very strong correlation to cognitive decline for those with AD.

1 Like
#103

I really dislike videos that are titled with “Thus far intractable disease is cured with this one simple trick”. So much so that I don’t even bother watching them. I would and I think others would, appreciate a few sentence summary about why you think the video is interesting.

10 Likes
#104

Sorry, its a new video from Dr. Bredesen. He does a really good job focusing on what has worked for Alzheimer’s interventions. A lot of it, he has already discussed, but this one really focused on the importance of Mercury and the oral biome, which both have a very strong correlation to cognitive decline for those with AD.

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#105

I’m presuming he has a lot more than this in his plans to diminish rates of dementia or even treat it.

I highly doubt that fixing everything dental, oral microbiome and treat HSV-1 if you have it will be the cure for Alzheimer’s.

These are all good things to consider and treat for sure.

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#106

Well, I’ve consolidated all the input and here is my updated and improved approach:
Dementia Risk Mitigation

Genetic factors to examine:

ApoE status

Get your genome sequenced (such as through 23&me) and upload your genome to Promethease.com. Genes/SNPs to look for include:

PSEN1

PSEN2

APP

TREM2

EPHA1

PICALM

SORL1

MS4A6A

Lifestyle options/labs/medications/supplements to risk mitigate for dementia

Lifestyle/Basic Items to Track

Use your brain to do complex things as much as possible. Passively watching things is fine for relaxation, but make your brain do repetitive hard work! It is likely that doing a substantial variety of tasks is beneficial as part of this.

Diet with more veggies, pholyphenols, flavonoids, limited extra virgin olive oil likely good, and fiber to >30-40 g/day

Limit or better yet eliminate artificial sweeteners

Minimize exposure to plastics – especially anything heated in plastic that you would then consume

No processed foods

Limit anticholingeric medications (for example Benadryl or Amitryptyline).

Limit or eliminate medications like benzodiazepines (Ativan, Xanax, Valium) or other similar (like Ambien)

Don’t smoke cigarettes or THC (or anything else)

Normalize hormones for life (some question on late introduction of estradiol in ApoE4 individuals)

Optimized blood pressure (SBP 110-120/70-77 mmHg), insulin sensitivity (HOMA-IR<2) and blood lipids (target to ApoB/Lp(a))

Optimize omega 3 index if ApoE4 positive then 10%, and vitamin D 70-90

Sleep monitoring to get at least 7 hours of sleep nightly, but not more than 9 hours. Be aware glymphatic activation occurs in deep sleep phase N3. Consider an Oura Ring or similar.

Regular aerobic exercise 150 minutes/week of zone 2, and 2 sessions of weight lifting (at least) weekly

Minimize alcohol and THC consumption

Optimize B12 (also measure MMA to confirm)

Look at Ferritin/HsCRP for any iron overload

Optimize peripheral lipids, but consider avoiding agents that decrease cholesterol in the brain

Optmize insulin sensitivity

Exercise 150 minutes zone 2 weekly, and 2-3 wt lifting sessions

Stay mentally active and socially engaged

Optimize Blood Pressure, goal 110-120/70-77 mmHg

Assess for chronic infections, particularly HSV-1, and if present treat this

Periodontal health optimization. If missing teeth, place implants. Check oral microbiome and if Porphyromonas gingivalis is present eliminate it and confirm on repeat retesting

The Lancet article https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01296-0/abstract discussed the following as risk factors, and if none were present 50% rate reduction of dementia:

Get more education

Avoid/Treat hearing loss

Avoid/Treat hypertension

Don’t smoke

Don’t be overweight or obese

Avoid depression, physical inactivity, Type 2 Diabetes, Excessive alcohol intake (>12 standard U.S. drinks/week), traumatic brain injury, air pollution and social isolation.it

Tests to consider

Aβ42:Aβ40 ratio and p-Tau181 are the only tests seen that are predictive of later dementia https://jamanetwork.com/journals/jama/fullarticle/2821669 - Note, can get both through LabCorp for $225 each

LabCorp pTau-181 483745: Phosphorylated Tau 181 (pTau-181), Plasma | Labcorp Test 483745

LabCorp pTau-217 test 484390 484390: Phosphorylated Tau 217 (pTau-217), Plasma | Labcorp

LabCorp A42/40 505725: Beta Amyloid 42/40 Ratio, Plasma | Labcorp. Labcorp test 505725

Omega 3 fatty acids goal 10% if ApoE4 positive, 8% otherwise

Vitamin D 70-90 ng/mL

Check for heavy metals, mold exposure, chronic infections (especially H pylori, HSV 1)

Consider Cunningham test or Vibrant NeuroZoomer (more cost effective) Well ProZ

Consider checking for environmental and other exposures, such as Vibrant total tox and PFAS

Total Tox: https://22446299.fs1.hubspotusercontent-na1.net/hubfs/22446299/Sample%20Reports/MK-0125-00%20Total%20Tox%20Burden%20Sample%20Report.pdf 1

Total tox includes mold, organic toxins/PFAS, heavy metals, environmental toxins

Consider chronic infections, Vibrant Infection panel and also Tick 1.0 or 2.0 https://hello.vibrant-wellness.com/hubfs/Tests/Viral-Infections/Viral-Infections-Sample-Report.pdf 1

Consider micronutrient panel (Vibrant) https://hello.vibrant-wellness.com/hubfs/Tests/Micronutrient-Panel/Micronutrient-Sample-Report.pdf

Consider Salivary Cortisol testing with ZRT or similar as abnormal cortisol levels and pattern will promote dementia

Medications/Supplements/Devices to consider:

Rapamycin/Sirolimus, if ApoE4, consider q14 day dosing with goal 100 hr level of ~3 ng/mL

GLP-1 agonist

SGLT2-i

Telmisartan

Low dose lithium

Fish/Algae oil with goal as above with Omega 3 index

Vitamin D optimize to 70-90 as above

Vitamin B2/Riboflavin

Turmeric/Curcumin/Black Pepper Extract Nanoparticle, NanoCur, 2 capsules daily Amazon.com

Ezetimibe could be useful

Hormone normalization for life

Methylene blue

Nattokinase/Serrapeptase

Dihydroquercetin – URL for buying here: Amazon.com: Supersmart - Taxifolin Dihydroquercetin 60mg per Day (90% DHQ Supplement) - Russian Siberian Dahurian Larch Tree Extract - Antioxidant Bioflavonoid | Non-GMO & Gluten Free - 100 Tablets : Health & Household 3

Ubiquinol or CoQ10 should be optimized given relationship of low levels with dementia

Phosphatidylcholine

Alpha Klotho – great at the point in time we can easily measure levels (Jfinity will test for ~$300). Work on driving it up with exercise/rapamycin

17 Alpha Estradiol

Astaxanthin https://us.fullscript.com/o/care-center/products/U3ByZWU6OlByb2R1Y3QtOTgwMjE=/U3ByZWU6OlZhcmlhbnQtMTE1MDg5 4

Black Seed (Cumin) Oil via Thymoquinone https://us.fullscript.com/o/care-center/products/U3ByZWU6OlByb2R1Y3QtOTM0OTc=/U3ByZWU6OlZhcmlhbnQtMTEwNDcx 1

Spermidine (Doublewood) 10 mg/day Amazon.com: Spermidine Supplement (10mg of 99% Spermidine 3HCL - Third Party Tested) 120 Capsules - Over 100x More Potent Than Wheat Germ Extract for Cell Membrane, Telomere Health and Aging by Double Wood : Health & Household

NT Factor Lipids NTFactor® Lipids Powder – NTFactor 4

Carnosine 500 mg daily Amazon.com: NOW Foods Supplements, L-Carnosine (Beta-Alanyl-L-Histidine) 500 mg, Healthy Aging, 100 Veg Capsules : Health & Household

NAC Ethyl Ester with Glycine, 1 capsule daily Amazon.com: N-Acetyl Cysteine Ethyl Ester 100mg - More Absorption Than 1000mg NAC - with Glycine 600mg - Benefit Glutathione - Good for Immune System & Antioxidant for Adults, NACET ( 60 Capsules - 2 Pack) : Health & Household

Creatine monohydrate, 5 grams dissolved in 8-12 oz of water daily Amazon.com: BulkSupplements.com Creatine Monohydrate Powder - Creatine Supplement, Micronized Creatine 1kg, Creatine Powder - Unflavored & Gluten Free, 5g (5000mg) per Servings, 1kg (2.2 lbs) (Pack of 1) : Health & Household

Berberine 500 mg daily (1 capsule) Amazon.com: Berberine Supplement 500mg, 60 Capsules (Third Party Tested, Non-GMO, Gluten Free, Vegan Safe) AMPK Activator - Berberine HCL for Cardiovascular Health by Double Wood : Health & Household

Creatine 5 grams daily Amazon.com

40 Hz light and sound

Article on 40 Hz vibrations reduce Alzheimer’s pathology, symptoms in mouse models | MIT News | Massachusetts Institute of Technology

Helmet with light Light therapy helmet for Parkinson's disease: the San trial results ex – SYMBYX Biome

Glasses with sound and light Amazon.com: Biothm 40Hz Gamma Light and Sound Therapy Glasses, Boosts Cognition Memory Mental Clarity : Health & Household

17 Likes
#107

Great thread.

I currently use a nightly dose of Mirtazapine for both sleep and histamine issues, which is safer dementia-wise than my old Promethazine regimen (I took that for three years). The switch wasn’t easy, but it went okay. Eventually, I’d like to stop Mirtazapine as well, but for now, I’ve been taking Citicoline in hopes of mitigating any cognitive downsides.

I recently came across an RCT published in the Journal of Nutrition showing that Citicoline (Cognizin) improved attention and mental energy. Could be interesting if you’re looking at ways to support brain health—especially if you carry APOE4/4 or otherwise want to be proactive about cognition. I’m open to stopping Citicoline if the evidence suggests it’s not that helpful, but for now, I’m giving it a try in case it offers some added protection against the Mirtazapine. Let me know if my logic is weak here.

2 Likes
#108

Is there any reason you prefer Phosphatidylcholine over something like Citicoline. I’ve done some surface level research on google and o1 and it seems to think Citicoline would be a better choice for preventing dementia and some other things.

It is hypothesized that, compared to choline moiety in other dietary sources such as phosphatidylcholine, choline in citicoline is less prone to conversion to trimethylamine (TMA) and its putative atherogenic N-oxide (TMAO). Epidemiological studies have suggested that choline supplementation may improve cognitive performance, and for this application citicoline may be safer and more efficacious.

o1 gives and an overview of it’s findings

Why Citicoline May Be the Better Neuroprotective Option

  1. Dual Precursor Advantage: Citicoline provides both choline and cytidine (becoming uridine in the body), which helps build neuronal membranes more efficiently than choline alone.
  2. Broad Mechanisms: Citicoline’s documented antioxidant, anti-excitotoxic, and membrane-stabilizing effects go beyond the basic membrane-support role of phosphatidylcholine.
  3. Clinical Trial Track Record: While phosphatidylcholine is known nutritionally, citicoline has been directly studied in stroke, traumatic brain injury, and neurodegenerative contexts with generally positive (though mixed) results.

*Yes I realise AI is not always correct but it’s becoming a more and more useful tool.

4 Likes
#109

Thank you for this. This looks like it will replace my phosphatidylcholine. Here is what Vera-Health.ai says on this:
Citicoline and phosphatidylcholine are both choline-containing compounds, but they have different roles and efficacy in the context of Alzheimer’s disease (AD) prevention.

Citicoline (CDP-choline) is a compound that provides precursors for the synthesis of neurotransmitters and structural phospholipids in neuronal membranes. It has been shown to have neuroprotective effects and is used in the treatment of cognitive disorders, including AD. Studies suggest that citicoline can improve cognitive function in patients with mild cognitive impairment and AD, although the quality of these studies is generally poor, with a significant risk of bias 3. Citicoline is also noted for its ability to cross the blood-brain barrier and enhance brain metabolism, which may contribute to its potential benefits in neurodegenerative conditions 7.

On the other hand, phosphatidylcholine (PC) is a major component of cell membranes and is involved in the synthesis of acetylcholine, a neurotransmitter important for memory and learning. However, clinical studies have not demonstrated significant benefits of phosphatidylcholine supplementation in improving memory or cognitive function in AD patients 11. The lack of efficacy may be due to the inability of free choline to significantly increase acetylcholine synthesis or release in the brain 11.

In summary, while both citicoline and phosphatidylcholine are involved in choline metabolism, citicoline appears to have more promising evidence supporting its use in cognitive disorders, including AD, due to its ability to enhance neurotransmitter levels and brain metabolism. Phosphatidylcholine, despite its role in membrane structure and function, has not shown significant benefits in AD prevention or treatment. Therefore, citicoline may be considered a better option for AD prevention based on current evidence, although further high-quality studies are needed to confirm its efficacy (ASHP).

6 Likes
#110

Thank you as always, Dr. Fraser.

Any thoughts on this 40Hz device from Koushicare in Japan? It uses gamma ray light passing through the skull — not visible light or sound.

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#111

I haven’t seen studies on this type of device other than from Vielight, but I would imagine that if it works, it only works on the surface level of the brain in the prefrontal cortex. Light in consumer devices does not penetrate very far (or often, at all) past the skull. And it’s not clear to me that the entrainment would extend to the rest of the brain just by hitting the prefrontal cortex. I would stick with the ocular/aural entrainment devices, unless they have a study that shows the same effect.

For context, to provide light energy deep into the brain you need a class IV laser, LEDs aren’t going to cut it.

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#112

Adding on to this, I would be more inclined to purchase a Vielight device if I wanted to try PBM. They have an ongoing phase 3 clinical trial for Alzheimer’s.

1 Like
#113

Which of their devices would you choose and why? Seems like a large number of options.

#114

Neuro Gamma 4 - this is the one they’re testing in clinical trials for Alzheimer’s and MCI. I suspect it primarily works (if it does indeed work) via similar mechanisms as the sensory entrainment devices. Ie - probably not light energy delivery directly but just enough light energy to cause an entrainment effect. Put another way, the 40hz pulse is probably more important than the joules delivered.

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#115

Full disclosure - when I first looked at Vielight 5 years ago, they were at the stage of case study research, so similar skepticism warranted as I have for NTFactor Lipids. I have not looked into their research since then, and only believe it might be interesting based on my assumption that the research done in the past 5 years must be fairly compelling to fund and run a FDA registered phase 3 clinical trial.

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#116

Consumer labs seems to recommend CDP-choline ( Citicoline) for Parkinson’s and eggs (mostly phosphatidylcholine) or alpha-GPC for Alzheimer’s. Or CDP-choline with galantamine. If taking substantial amounts of any of them I would make sure it doesn’t raise TMAO levels from your baseline for more than a few hours. (IE Take test after fasting overnight from having any). My baseline is very low from just having occasional eggs, but I probably do need more choline.

3 Likes
#117

FWIW: I have tried both extensively, and I agree, citicoline definitely seems to give me more of a mental boost over phosphatidylcholine. For some reason, maybe age, I seem to be very choline sensitive. If I forget to take a choline supplement, my short-term memory starts to suffer right away.

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#118

Because being half as healthy as you are at your age is my stretch goal, I’ve just ordered some. How much do you take? 500mg?

1 Like
#119

Wow. Very good job updating this.

I would add that many of those genes listed can only be found using a whole genome sequencing (WGS), which you wouldn’t find on 23andme or most other services.

You can use https://nebula.org/ and purchase their WGS for around $400, then upload it to Promethease. This is what I did. I actually found out I had a very rare PSEN2 variation, which potentially caused very early onset AD. But after doing a lot of independent research, I found out it had pretty much no effect. lol.

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#120

How did you do this?
Did you upload the whole cram file (60 GB)?
I tried several times to upload the VCF file but is wasn’t accepted due to invalid header information.

1 Like