Bredesen and de la Torre (and G-L) divergence

[Larsmars11]

as someone who gave 9 copies of "The End of AD" to family and friends, it would b wonderful to think that Dr. Bredesen has essentially solved the mystery of AD, to the exclusion of other theories of it, such as the "vascular hypothesis" of Jack de la Torre and Francisco Gonzalez-Lima at Texas. I'm probably one of the few here who has read "Alzheimer's Turning Point, 2016, (an $80 paperback ripoff) so I am aware of some of the differences. bottom line, I think it would b a mistake for members here to rely only on Bredesen's overall point of view. both camps share a belief in the importance of a ketogenic diet, daily fasting, lots of exercise good sleep and the evils of excessive homocysteine, and a few other things. but the vascular hypothesis says Abeta plaques and tangles r a secondary effect and that greatly reduced cerebral blood flow caused by aging and cardiovascular issues r the primary cause. Bredesen never mentions reduced cerebral blood flow , and it and cardiovascular issues r NOT one of his 36 or 45 "holes in the roof". sorry, gotta go now, more later. L.3/4

[Plumster]

Thanks, Larsmars, I agree that the cardiovascular model is underrepresented and needs more emphasis. The research from Finland on sauna use and the significant decrease in AD may be explained by the removal of toxins from sweating, in part, but I suspect the health of your arteries and blood flow are important benefits from the sauna, too, just to name an example.
Study: https://www.ncbi.nlm.nih.gov/pubmed/27932366

[Larsmars11]

Bredesen says growing evidence that neither amyloid plaques or tangles is the cause of AD, yet nearly his entire thesis hinges on the 2 ways he believes APP, as a dependent receptor , can b cleaved. de la Torre never mentions "dependent receptor" (probably should have), because old mice w induced reduction in cerebral blood flow get cognitive decline and neuronal death w no Abeta present, and autopsies of old, cognitively normal people cannot b differentiated from those who had AD, in terms of Abeta plaques and tangles observed. several studies have shown one can have plaques and tangles and no AD as long as there is no major reduction in cerebral blood flow (chronic brain hypoperfusion). de la Torre says flatly Chronic brain hypoperfusion is the major cause of AD and the major risk factors for hypoperfusion r vascular, such as hypertension, artherosclerosis, congestive heart failure, atrial fibrillation and a dozen other heart and brain artery related problems. 50%+ of AD patients have MODIFIABLE cardiovascular risk factors which can b targeted to slow the onslaught of AD. that seems huge. there is much, much more I could mention about the vascular hypothesis, but I believe it was a mistake for Bredesen to completely ignore it, because it has a lot of credibility. de la Torre thinks gov't funded Heart-Brain Clinics is the way to go if we r serious. I may as well go further out on a limb and say I think there could well b major modifications in Bredesen's second book. The "holes in the roof" concept could b cut in half or scrapped (way too complicated). even the "3 kinds of AD" could b scrapped, because apparently he now says toxins account for 50-60% of AD, and most AD is a mixture anyway. and I think for credibility he will have to deal head-on w the Vascular hypothesis, as well as going into these recent gene editing and gene modification procedures. and there is a fair amount of new research being done in the vascular area. the first book may look semi-obsolete when the second comes out. I certainly could b spectacularly wrong. but, hey, I'm here primarily to learn anyway. comments appreciated. L. 3/4

[Jlhughette]

I was wondering why Francisco Gonzalez-Lima does not mention or recommend hyperbaric oxygen as a treatment for vascular dementia, since his primary culprit is cerebral blood flow diminishing. Paul Harch MD wrote a compelling book called ‘ The Oxygen Revolution’ in which there a several examples of dementia from various causes turning around after many rounds of treatment with hyperbaric oxygen. The book is not solely about AD, but how HBOT can be used for a wide range of conditions where tissues have been damaged by deprivation of oxygen. He is best known for treating brain injuries. But if you dig deep into the book there are several spectacular examples of reversal of dementia. I suspect that the reason it is not discussed more often is the perceived expense of the treatments. Any thoughts?

[aphorist]

Couple quick thoughts:

1. Bredesen's viewpoint does indirectly support the vascular view of Alzheimer's in that he prescribes exercise and ketosis (Ketoflex) does improve cerebral blood flow.

I think the issue is that Bredesen sees a constellation of Alzheimer's amyloid/tau pathology being caused by potentially different initiators including mold/CIRS, hormonal imbalance, and viral infection (HSV), such that the downstream event of how APP is process is a unifying event of many different causes.

2. Hyperbaric works. I've done it and I've read 8-10 papers on it. It's highly stimulative of neurogenesis, blood flow, and repair. It's being used in Israel as an anti-aging therapy to prevent and reverse cognitive decline in all kinds of patients (TBI, etc.). I think the problem is getting insurance companies and medicare to cover it. And there are no lobbying groups in Washington DC with the kind of money that Big Pharma has to try to get payments for it. Because it's probably better than current drugs.

[Larsmars11]

Roher 2011 found a major narrowing (80% or more) in many autopsies of AD patients in the circle of Willis artery (brain) versus only minor narrowing in cognitively normal patients autopsies. same was true in internal carotid and vertebral arteries. seems clear atherosclerosis is a major risk factor for AD, supporting vascular hypothesis and is independent of how APP is cleaved.

[mike]

Isn't one of Bredesen's three types of AD lack of nutrition to the brain? I've been breaking things up in my mind as two main issues. Nutrition, which includes blood flow, but also mitochondrial issues and glucose transport issues and ketones. Neurons are dying or losing connections. Some become zombie cells and become toxic, possibly as a result of Tau? On the other side you have blood brain barrier issues. It is being broken down over time and from the result of many insults discussed by Bredesen. This leads to AB as it tries to defend the brain as the BBB becomes leaky. For those without APOE4, this stuff gets cleared out during deep sleep. APOE4 carriers don't clear it well, and it builds up, probably causing issues. The amount of cognitive decline will depend on how much and where the neuronal loss happens compounded by AB and more likely tau buildup. ApoE4 seems to effect both the nutrition side of things by causing glucose to be metabolized less well, and then by slowing clearing of garbage from the brain during sleep. Instead of one seesaw, there could be two or three. The first being nutrition to the brain, and then attacks to the BIBB, and then clearing during sleep.

[Julie G]

I finally finished the interview with Dr. Gonzalez-Lima, and I'm more convinced than ever that he and Dr. Bredesen are discussing different sides of the same coin. Both see AD as a mitochondrial crisis. Gonzalez-Lima views it from the perspective of chronic or acute HYPO-perfusion of cerebral blood that leads to oxygen deprivation; whereas Bredesen focuses more on the reduction in cerebral glucose utilization that leads to a HYPO-metabolism of the brain In both instances, the brain is deprived of the fuel it needs- given that blood carries both oxygen and glucose. I also find it encouraging that both come up with VERY similar prevention/treatment models: reduce CAD risk factors, exercise, fast, & a ketogenic diet. I'll recommend that Dr. Bredesen take a listen and let you know if he has any interesting feedback.

[Larsmars11]

Julie, the only reference to mitochondrial function in "The End of AD" I could find was 1 1/2 pages which did not mention reduced cerebral blood flow or glucose at all, but referred simply to several chemicals that can damage mitochondria such as antibiotics, statins, alcohol, NSAIDS, cocaine and a few others. perhaps he told u orally that AD is a mitochondrial crisis, but the book doesn't reflect it. I doubt bigly that Bredesen would listen to egomaniac Attia's 2 hour podcast w G-L, since B is already totally familiar w the vascular hypothesis. I would much rather know from him y "reduced cerebral blood flow" and cardiovascular issues were not included in his list of 36 or 45 " holes in the roof", since they r extremely important. and the $64 question- how widely believed is his "dependence receptor and APP 2-way cleavage" theory among top scientists ? ( is that partly the basis of the oblique UCSF criticism or just professional jealousy ?) I greatly respect ur vast AD knowledge- my is only half-vast. thanx. L.

[Julie G]

Lars, it's very clear to me from reading the book that his whole approach is designed to upregulate mitochondria. That's certainly the rationale behind the diet, the long fast (autophagy), exercise, various supplements, etc. I think that's generally clear, not a secret that he shared with only me.

I'm feeling rather dense at the moment, but I've never seen a list of the 36-45 holes. Have I missed it? I think it's more of an analogy to describe the idea that there are multiple possible contributors to AD. All of Dr. Bredesen's testing and strategies are designed to overcome them. Many of his tests and strategies specifically address vascular issues including hs-CRP, homocysteine, Omega-6:3 ratio, A/G ratio, fasting insulin, glucose, HbA1c, LDL-P and sdLDL, oxLDL, TC, TGs, blood pressure, BMI, etc. His LDL-P goal of 700-1000 and sdLDL goal of less than 20 are MUCH stricter than Dr. Gundry's.

and the $64 question- how widely believed is his "dependence receptor and APP 2-way cleavage" theory among top scientists ? ( is that partly the basis of the oblique UCSF criticism or just professional jealousy ?)

Of course, I have no way of knowing that Lars. I suspect that much of the criticism is simply protecting turf. Dr. Bredesen, largely because of his practitioner wife, has pierced the veil of translating science to clinical practice. That's pretty much unheard of in this field with the standard of care to offer one or a combo of several drugs that do nothing to change the trajectory of the disease process and may even harm the patient. (Dr. Bredesen would agree with Dr. Gonzalez-Lima on that one.)

I doubt bigly that Bredesen would listen to egomaniac Attia's 2 hour podcast w G-L, since B is already totally familiar w the vascular hypothesis.

Hey, he might. Dr. Gonzalez-Lima presents the vascular hypothesis in a completely new and refreshing way. Until now, it's been largely thought of as a separate disease process associated with a blockage of blood to the brain as seen in a patient with a stroke, series of TIAs or MI. Dr. Gonzalez-Lima does a great job of connecting it to the broader AD category. I'll let you know if I get any feedback from Dr. Bredesen. BTW, I don't think Dr. Attia is an egomaniac. I think he's super smart and always worth a listen.