ApoE4.Info

Brian4 wrote: ↑Wed Jul 27, 2022 10:48 pm As it happens I had my annual NeuroQuant scan done a couple weeks ago, and met with the radiologist yesterday. I asked about gray matter changes, and he pointed out that gray matter volume can sometimes increase dramatically if one is sick. Looking at particular regions is key to interpreting the meaning of gray matter changes. The caudate nucleus, for example, would typically get smaller if the brain as a whole is inflamed, then would return to normal afterwards.

Bredesen presents the case of an internal medicine physician in this grand rounds lecture starting around 28:45. The patient's hippocampal volume scan showed a dramatic increase and his behavior correlated with the volume increase. So going on your theory, perhaps his brain was very inflamed and the Bredesen protocol reduced the inflammation leading to an apparent volume increase and also a dramatic improvement in cognitive behavior. He also went off the protocol for a while with his cognitive behavior declining and then returned to the the protocol with a positive return to good cognition. Whether the volume actually increased seems less material than the positive improvement in cognition.

So I see some common ground among various views---and I need to step up my step intensity!!

Nice sleuthing and me too on the exercise. I love getting in 3.5-4 miles daily, but too often life gets in the way.

Speaking of inflamed brains, I have COVID-19 (minimal lung involvement, so I'll be fine), so I'm too exhausted to look at Bredesen's paper, but if someone with a non-inflamed brain can look into this, s/he may discover evidence that the cases of apparent miraculous gray matter recovery may just be cases of people who were ill in some way

So sorry about the COVID, my friend — extra scary with the E4s. Please take care of yourself. I have so many friends who felt better, then ultimately overextended themselves for a bigger relapse. Take it slowly. I also think you're onto something with the notion of "illness" causing a reduction in volumetrics. Bredesen addressed multiple chronic illnesses (such as metabolic syndrome, obstructive sleep apnea, hyperhomocysteinemia, etc.) over the 9 months which, combined with the exercise, cumulatively may have led to the improvement.

The journal is a super crappy one, yes. Why publish there if you've got genuinely valuable, reproducible results?

Interesting. I was unaware that this is a "super crappy" journal. if true, perhaps it's because more mainstream journals wouldn't accept an alternate hypothesis (?) Just guessing. That inability to publish non-pharma treatment in prestigious journals was laid out nicely in Fung's blog.

Regarding the attack on the establishment - it is indeed sad that there's been no progress yet, and that drug companies can get useless drugs on the market if they're insistent enough, but since you mention HIV let's not forget that the first HIV drug was a disused cancer drug that made it through a vast screening effort that took years to complete, and that while it was effective it also had terrible side effects and only offered a decade of additional life (and was quite expensive by 80s standards) - and yet none of the "alternative" treatments offered from outside the establishment ever worked - the only thing that did work was more pharma research.

Good point. Let me clarify, I wasn't as much pushing for non-pharma options (although they seem to be the most effective for AD so far) as much as I was suggesting that we borrow from the playbook of the early AIDS activists and band together to push policymakers to accelerate a treatment, see How To Demand A Medical Breakthrough: Lessons From The AIDS Fight. I'm certainly not opposed to pharma — whatever works!

Julie G wrote: ↑Thu Jul 28, 2022 1:08 pm So sorry about the COVID, my friend — extra scary with the E4s. Please take care of yourself. I have so many friends who felt better, then ultimately overextended themselves for a bigger relapse. Take it slowly. I also think you're onto something with the notion of "illness" causing a reduction in volumetrics. Bredesen addressed multiple chronic illnesses (such as metabolic syndrome, obstructive sleep apnea, hyperhomocysteinemia, etc.) over the 9 months which, combined with the exercise, cumulatively may have led to the improvement.

Thanks Julie. Today is Day 13. Still testing positive, but my only symptom (for a while now) is exhaustion. I'm definitely not going to push it! Overexertion during COVID recovery seems to increase chances of getting long COVID.

By the way, the point the neurologist made was that a decrease in overall gray matter can be a good thing: it can mean that brain inflammation has resolved. Key to interpretation is looking at changes in particular subregions, such as the caudate nucleus.

But yes, cognitive functioning is of course what really matters!

Hugs from quarantine,
Brian

By the way, the point the neurologist made was that a decrease in overall gray matter can be a good thing: it can mean that brain inflammation has resolved. Key to interpretation is looking at changes in particular subregions, such as the caudate nucleus.

I bet in some cases (depending on the region as you point out) that might be true. It seems unlikely to me that nine months of optimizing health would result in illness throughout the dataset, but who knows? I reached out to Dr. Raji to share your hypothesis. If I get a response, I'll share it.

I pray that you test negative soon. For my husband, it took 14 days. I didn't want him to return home until he was negative. He was away from home when he tested positive so he ended up with a 2-week COVID holiday at the Marriott watching war movies and laying around. He actually looks back on that time fondly Healing hugs headed your way.

Julie G wrote: ↑Fri Jul 29, 2022 9:29 am It seems unlikely to me that nine months of optimizing health would result in illness throughout the dataset, but who knows? I reached out to Dr. Raji to share your hypothesis.

I wonder if what was meant is that the people had illness (or inflammation) during the initial scan, showing reduced volume, Then, with improvement in said illness or inflammation, a second scan would show a larger volume?

I think Brian is suggesting the opposite, that increased volumetrics could be the result of inflammation and resolution would result in reduced grey volume. I checked with Dr. Raji and he pointed to this study as an example of Brian’s theory: https://pubmed.ncbi.nlm.nih.gov/24946038/.

His comments:

I'm not sure I buy the increased gray matter volume story as a marker of neuroinflammation which is the idea in Shoemaker's studies. He found those data with an older version of NeuroQuant and to my knowledge those findings were never replicated with any other software so I wonder if it's a software issue. Also important to look at the totality of evidence — overall biochemistry (including hs-CRP) improved, statins, anti-hypertensives, and other meds discontinued; and multiple cognitive improvements. To suggest “illness” in the presence of a clinical picture depicting the opposite doesn’t make sense.