HBA1c, what is ideal

[Julie G]

This is what work of Zlokovic and Ai-Ling Lin is all about. Saying these changes in cerebral blood flow as measured by glucose uptake on PET scans are due to cerebral insulin resistance is to interpret what is happening as 100% wrong.

Fascinating discussion. Why is it one vs. another? Glucose is carried via the blood. Wouldn't it follow that a reduction in CBF would lead to a reduction in cerebral glucose availability? Perhaps bolstering Alan's position is the fact that E4 carriers, as early as our 2nd decade exhibit these changes. Would IR be present then? In modern Western society, I suspect the answer could be yes. It would be interesting to scan two groups of young E4 carriers; one a typical group of Americans, the other a group like us, hyper-focused on health. I suspect the latter wouldn't demonstrate a difference in either CBF or reduced glucose utilization... wild guess on my part.

That said, Reiman (2013) has clearly established the inverse correlation between peripheral hyperglycemia/IR and cerebral glucose utilization. In terms of translating this to our clinical strategies, we need to focus on increasing cerebral blood flow (exercise) and preventing IR to avoid AD. It's not an either/or.

Thank you, Susan & Theresa, for jumping in to remind us all to remain respectful when discussing and interpreting the science. There are many unknowns surrounding the APOE-ε4 gene. I appreciate having a safe place in which to translate the science into clinical strategies.

[alangreenmd]

Hi Julia,
The 2016 summary paper by Lin, in which quote portion of first paragraph shows why worth the effort:

"APOE4 carriers accumulate beta-amyloid and neurofibrillary tau tangles earlier and with more extensive pathology compared to non-carriers, However, decades before the aggregation of AB and tau, cognitively normal APOE4 carrers have developed neurovascular deficits, including reduced cerebral blood flow and impaired BBB integrity. (Bell, 2012). The above indicates that brain physiology is altered in APOE4 carriers before clinical markers such as AB, tau pathology and memory deficits appear, suggesting that vascular changes predispose APOE4 carriers to developing AD. Therefore, early interventions that can restore neurovascular deficits to normal could be critical in potentially preventing the development of AD-related neuropatholgy and cognitive impairment."

[Stavia]

Alan, you have thrice ignored polite requests to back up your theory with data in apoe4 human patients on your rapamycin protocol. Anonymous obviously.
What I am interested in are advanced markers such as HS-CRP, tnf-alpha and interleukin-6 in apoe4 patients showing improvements come from only addition of rapamycin to an already optimal lifestyle and diet.

In addition evidence is suggestive that graphic factors such as D3, TSH, oestradiol and cofactors such as zinc, B12 and of course the methylation pathway etc etc play a role in AD. Are you tracking these in your patients?

Do you have any data of this nature in apoe4s to share with us?

I have read your personal testimony and am very pleased you are enjoying good health and an active lifestyle in your 70s but I am requesting more human data.

We are able to optimise glycaemic control and keep insulin low by means other than rapamycin. I am not particularly interested in basic lipid or haematological panels as I personally am not impressed by evidence that basic lipid profiles are a player in AD.
Your improved creatinine is interesting but the higher reading may have been an outlier.

I fully understand that you are not in favour of all opposing theories to your favoured one. Even those of Bob Mahley who has spent his entire acclaimed career working with apoe4 after he was the first to identify its isoforms. (He is a lovely person, an intellectual giant and a complete gentleman, we spent a day with him at his lab a few years ago. I respect him and his team enormously https://gladstone.org/our-science/people/robert-mahley).


Here is a fourth request to share some of your applicable data with our community, if you wish.




Sent from my SM-G930F using Tapatalk

[Julie G]

Interesting, Alan, but I'm not sure that it's PROOF that the reduced cerebral blood flow causes the damage vs. the reduction in cerebral glucose utilization. Given that glucose is carried by the blood, this feels like a chicken/egg debate. Out of curiosity, have you been following this thread, starting by Edward Blond, Ph.D? I suspect that he might disagree with your interpretation of the science.

[Tincup]

I wouldn't mind going both routes. I personally feel better on a carb restricted, healthy fat diet with lots of greens and veggies. But also I would love to incorporate any suggestions that would increase blood flow to my brain. I typically have low blood pressure, with systolic under 100. Does that seem problematic? Any other suggestions from other members? Thanks in advance.

Assuming you mean your low BP is somewhat symptomatic? If so, perhaps low blood volume is an issue. A female friend who was tall, thin, and had low BP fixed her symptoms as directed in this article.

[alangreenmd]

Hi Julia,
Thanks for directing my attention to "thread".
I agree with you 100%; he would not agree with me.
I am basically a mouse person; but also like autopsy studies of human brain.
I don't like theories, unless theory comes from somebody born in St. Petersburg, Russia.

[Stavia]

Hi Julia,
Thanks for directing my attention to "thread".
I agree with you 100%; he would not agree with me.
I am basically a mouse person; but also like autopsy studies of human brain.
I don't like theories, unless theory comes from somebody born in St. Petersburg, Russia.

I think we got that already Alan.

Please let me make this absolutely crystal clear.

This community exists because there are still many horses in the race and it isn't over. You have placed your bet with confidence. I personally do not intend to make the same bet as you at this stage. I do not feel there is currently enough evidence to have an entrenched position and I am extremely wary that I may be prey to confirmation bias if I am dazzled by the next bright shiny thing. I have read your entire website and I await human data .

This community does not allow members to criticise the decisions of other members. Denigrating the work of other scientists by inference denigrates the decisions of members who have chosen to follow them. I am saying this as a Board Member and Moderator.

[chrissyr]

Assuming you mean your low BP is somewhat symptomatic? If so, perhaps low blood volume is an issue. A female friend who was tall, thin, and had low BP fixed her symptoms as directed in this article.

[/quote]

Thank you Tincup! Interesting. My symptoms are not too bothersome, but they would trouble me if it meant that sufficient blood flow was not getting to my brain. My mother (has AD) actually had sudden"heart block" --- and had a pacemaker placed last year (otherwise very physically healthy) She is on a beta blocker for migraines. That may all be unrelated but somehow seems related. I have the feeling of heart skipping a beat and dizziness when rising too suddenly. Sometimes fuzzy brain

Thanks again, drinking water and will get out the salt shaker

[Tincup]

. I have the feeling of heart skipping a beat and dizziness when rising too suddenly. Sometimes fuzzy brain

For the skipping beat, sometimes extra magnesium may help. Whatever form you like. If you try it, suggest increasing dosage till your stools start to get a bit loose, then back down just a bit. I've actually kept atrial fibrillation in remission almost completely at bay since 2004 using this technique and have taken many times the 400 mg/day RDA in the process (currently taking around 2.5g/day).

[Julie G]

I don't like theories, unless theory comes from somebody born in St. Petersburg, Russia.

Lol, I think you mean Belgrade, As Stavia points out, because the science around our gene is emerging, we respectfully entertain ALL theories... including yours. Our lives are literally on the line. Folks tend to get intimidated when members with an "MD" in their forum names are very certain that they have the answers. FWIW, many of our members are physicians, scientists, researchers, and lots of very smart laypeople. We're a self-selected group of "citizen scientists" taking our health into our own hands because the medical community doesn't have an agreed upon consensus for us. We're delighted to have you partake in the conversation, but we need you to have a broad understanding of the big picture and understand how vulnerable some of our members feel. We appreciate you trying to offer help, but please remember that there are likely multiple pathways to the same end.