Dr. Bredesen with Chris Kresser

[circular]

A really good new interview with Dr. Bredesen. It's fun listening to each of them as they come out and hearing the evolution of his ideas.

[circular]

The question came up some time ago about Dr. Bredesen noting he didn't want to see insulin go too low. I've been thinking that's because it's neurotrophic. In this interview he says insulin is 'one of the most important' neurotrophic factors. So I'm thinking that if one can establish they are insulin sensitive, it may be useful not to go or stay too low carb. Have yet to hear where Dr. Bredesen would like to see our fasting insulin level, but it may be different depending on one's insulin sensitivity status, in which case I'd like to know exactly what parameters he uses to assess insulin sensitivity too.

[circular]

Several other takeaways:

He likes NeuroReader more than NeuroQuant since the former measures more areas (39 regions), but I think he said he liked having either rather than neither.

His software algorithm will input data from over 100 historical, biochemical, genetic, imaging and function values and give the % contribution for each of the different AD pathology subtypes.

I think he said he's finding people with CIRS+ lab results but who don't experience typical CIRS symptomatology. He suggests that CIRS testing is a doorway to innate immune activation beyond biotoxin infection???

[circular]

He also describes how the nasal microbiome is getting a lot of attention and noted that the nose has a more direct route to the brain than the gut. MARCoNS would appear to be crucial to evaluate in anyone with chronic rhinosinusitis not responsive to an antibiotic.

The AD types as he lays them out here:

Type 1:

(Non-CIRS) infections and sterile inflammation 'liberate' amyloid as protective

Type 2:

Reduction of trophic support leads to neural downsizing.

Type 1.5:

Insulin resistance contributes to reduction in trophic support, since insulin is 'one of the most important' neurotrophic factors, while increased AGEs, driven by hyperinsulinemia/glycemia feed inflammation of the type seen in Type 1.

Type 3:

Toxic exposure: mycotoxins, CIRS, lyme ... A more cortical presentation.

[circular]

Chris states that LDL is antimicrobial

[Julie G]

Really good interview, Circ. Thanks for sharing. FWIW, at the last physician training, I was surprised to learn that he's actually categorized 2 additional subtypes:

Type 4:
Vascular

Type 5:
Associated with TBI

Your question with re. to insulin is a good one. In this interview, he refers to it as being too low (or unavailable) due to IR, but I've also heard him refer to it being "too low" after patients improve metabolic biomarkers. It seems to me that we may be dancing on the head of a pin, trying to optimize glycemic markers and create ketones while keeping insulin high enough to provide trophic support. There is a new training coming up at the end of the month, I'll try to push him on this point to get specifics of what constitutes TOO low.

I was, once again, struck by his focus on the pro-inflammatory effects of ApoE4 and how that affects our innate immune system. This is what makes me nervous about maintaining a higher LDL-P or ApoB... Yet, LDL itself, has antimicrobial properties??? Fascinating.

[RichardS]

Several other takeaways:
His software algorithm will input data from over 100 historical, biochemical, genetic, imaging and function values and give the % contribution for each of the different AD pathology subtypes.

I caught that, too. My first thought was wondering how many subjects does he have in that database on which the algorithm was based. It appears to be some sort of regression model. One of the basic lessons of regression modelling is that it is important to have proportionally more subjects for each variable in the model, otherwise it can be very easy to get spurious results, and 100 regression variables is a lot for any researcher to handle reliably. I have not heard that the algorithm has been published. There may be some intellectual property protecting it. Still, my impression of the size of his operation concerns me that the algorithm is not ready for the clinic. I really hope he can publish a sizeable study with it with strong validation.

Richard

[RichardS]

I liked his comments about the clinical research to date on reducing beta-amyloid not yielding much and that looking to the cause of the amyloid buildup should be a greater focus.

[circular]

Hi RichardS, always love your trained input. At least he does say that his 100+ subjects don't make for good statistics. I'm hoping it will turn out to be a blessing in disguise that he hasn't gotten a review board to approve a clinical trial yet. Maybe when the time comes for that it will be more robust for his pioneering, if imperfect, efforts now.

Sometimes problems are best solved by approaching something from a different angle. I propose that Dr. Bredesen get help from NASA engineers. I figure if they can make all the variables line up right such that Juno can successfully make it into orbit within Jupiter's gravitational field, then the big data of personalized medicine can be processed by a properly written mega algorithm. I just wonder if it will take a real rocket scientist I love the idea of a NASA/Bredesen Partnership Against Alzheimer's

[circular]

It seems to me that we may be dancing on the head of a pin, trying to optimize glycemic markers and create ketones while keeping insulin high enough to provide trophic support. There is a new training coming up at the end of the month, I'll try to push him on this point to get specifics of what constitutes TOO low.

Oh, please do, TIA!