Skill Testing AD Question from JAMA

[J11]

In a recent issue of JAMA, they present a patient with APOE epsilon 34 with subjective memory complaint with a strong family history of Alzheimer's 10 years before typical family dementia onset.

This is one of those "what would you do if you were an AD clinician" quizzes:

"What Would You Do Next?

Obtain a brain fluorodeoxyglucose positron emission tomography (FDG-PET) scan.

Order cerebrospinal fluid (CSF) testing for Alzheimer disease biomarkers.

Reassure and address patient’s concerns and follow up in 1 year.

Refer for genetic counseling. "

I'll give the answer below but I'll give everyone a chance to contemplate and answer this skill testing question.
No pressure; it's just that everything is on the line here for the fine opinion of those on the APOE 4 forum.






APOE ɛ4 Allele Testing and Risk of Alzheimer Disease
JAMA. Published online January 14, 2021. doi:10.1001/jama.2020.15085



And the answer is: "Reassure and address patient’s concerns and follow up in 1 year."
What? Oh, man how can you crash and burn on something that you know on a deep personal level?

Watchful waiting? Are they kidding?
There are a whole bunch of fairly intense 34s on forum who want to do a whole bunch more than watchful waiting.
The patient is 10 years within onset!
Why be so insouciant about approaching cognitive decline?

We need to go beyond the textbook answer!
What do We The People of Dementia Nation have to say?


Low dose reduced methylene blue?
Gamma entrainment?
Beg for Aducan (or enrol in trials eg. Ban2401, dona etc.)?
Sign up for APOE 4 forum and learn from the experts!
inter alia

[Julie G]

I saw that too, J11. I also found the "answer" to be underwhelming. There is so much you can do early in the disease process. Our biggest hurdle may be getting information to the "experts"... sigh.

[floramaria]

And the answer is: "Reassure and address patient’s concerns and follow up in 1 year."

Woah! That “right” answer is so wrong! It is born out of the “there’s nothing you can do about it anyway” approach.
I think the correct answer is “ advise patient to start by visitIng the ApoE4..Info Website.”

[J11]

Julie G, it is very much appreciated that there is an internet forum that any day any time that the dementia community can talk dementia. Dementia 24/7. All Dementia; All the time.

Big Tent society is no longer plausible. I have contacted extended family through the online genotypers and when I asked about any AD in the family all they could reply was: What is dementia?

OK Yeah, whatever, What's the point? What's the point of a broad society when we are all on different flight plans?

Nevertheless I still found it quite impressive that not only had you seen the JAMA article but that you were likewise unimpressed with "the answer". This is considered an "expert level answer"? I have arrived at the conclusion that if I need expert level help, I should consult the experts like those on this forum (you, floramaria etc.). The authorized answer: Do nothing is abysmal. In one of trips to the hospital one of the nurses explained how much she truly hated her medical education and only got through her training because at the end of it she knew she had a 70k job for life. Extrinsic motivation will never make you happy and it will never make you a true expert. When the exam are over you need to want to keep searching out for answers. Apparently, that nurse never did find happiness in what she was doing. Find something that you love doing and then find a way to be paid for it. This seems to be the recipe of life success more than starting at the end and working forward.

Having an internet cafe where one serves and others return volley is enormously appreciated. I also agree that there is much that can be done in the early stages that apparently current medical training does not recognize.

Of the answers given "Refer for genetic counseling" seems the most sensible.
We know that the genetics of Alzheimer's is much more complicated than simply APOE epsilon 4 positive or not.
Establishing the AD polygenic score would be a great place to start.
Next move would be to go full genome and look out for rare variants that look risky.
The especially worrisome variants that were not reported in the GWAS could then be followed up with
contacting extended family on GEDmatch etc..
It appears that a super-rare variant could be at play in my family.

There then a wide range of possible interventions that could then be tried as discussed on this forum.
Remarkably it is this very patient advocacy and participation that has helped "invent" an early intervention for AD.

I regret not being more bold when taurx announced methylene blue at the 2008 ICAD.
https://www.alzforum.org/news/conferenc ... eatment-ad

I saw this item at that time and yet it is always so confusing to know what to do.
Here we are 13 years later and the final headline is still yet to be published, though methylene blue clearly now does appear to be a breakthrough treatment.

It is all of this uncertainty that makes it so confusing. When everything is sorted out, preventative/curative AD treatment might only require a one paragraph entry in the Merck Manual, though we have been struggling for years to try and anticipate what the recipe might be.

I actually went to medical school. Er, by that mean I loitered in the hallways of a medical school before security was able to locate me. I developed the impression that medicine was not for me. My impression was that medical schools really did not understand what 21st Century was going to be about. Medicine needs to constantly reinvent itself to stay relevant, though what I absorbed osmotically in my trespass was that this would not happen. Medicine would not find its way to the leading edge of modernity. Surprisingly, I am unclear whether even now there is a title such as MD of Alzheimer Medicine. Yet, AD is the pandemic of the 21st Century. This for some reason is a somewhat obscure observation.

Instead of focusing on reality, medicine largely has continued to understand the world in terms of infectious illness. COVId might seem to be a validation for this perspective, yet upon further reflection this is not entirely true. For the full sequence of COVID was found within ~ the first month of the pandemic; an RNA vaccine for COVID was rapidly produced (within ~ 1 month). Emergent infectious illnesses (such as COVID) should not be thought of the future of medicine, but the past. If another infection like COVID were to arise, it is possible that vaccination could begin even before the first wave hit.

It is very disappointing that medicine has embraced the action movie vision of reality (epitomized by COVID) and not the more mundane yet truthful reality of dementing illness.

The JAMA suggested response to the skill testing question further highlights for me how out of touch the mainstream really is from the leading frontier of AD thinking.

Education according to the plan of:
"Repeat after me." "Repeat after me."
"I state your name." "I state your name."

Ugg!

I am glad I missed out.
It seemed so out of tune and it still does.
If I had to do it again I am now leaning to the model that you and Stavia have embraced.
Go all over the world and attend extremely interesting lectures by the thought leaders in your field.
This would be fantastic!
Basically blow a million dollars and have the best time of your life. (though mouching the million from your parents, the government or the banks might need some finesse.)
Admittedly, the girls having fun model would be more psychologically difficult to replicate in the other gender.

[J11]

floramaria, yes Do Nothing is a hopelessly wrong answer.
I think with multiple choice questions it would make so much sense to modify the format to include
choices A,B,C,D and an explanation box. Sometimes the answer is clear, though occasionally the given
choices really are not all that good. The explanation box could then offer the opportunity for students
to provide background reasoning for an alternative answer. A well-reasoned alternative could be superior to
all given choices as would seem clear with the JAMA question. Probably the best way forward for education
is to embrace AI based marking. Find out what students truly know instead of how they fill in the bubbles.

We probably should try and locate a final exam for a medical school Alzheimer's Disease course (if they even have such
a course!). I am afraid that if anything the correlation between the "official" exam score and the exam score as judged by the expert collective opinion of the forum might be negative.

[floramaria]

I have contacted extended family through the online genotypers and when I asked about any AD in the family all they could reply was: What is dementia?

Like you, I am grateful for this community and the opportunity to dig deep and to learn and to discuss ideas with like-minded people. Or perhaps “like-minded” is the wrong phrase, since I also appreciate the diversity of opinion; “similarly committed to and invested in seeking answers” is more accurate. One of my most painful experiences in the last decade was telling a dear friend who was just beginning to have cognitive problems that were things she could do to slow or reverse the decline. Both she and her husband said they weren’t interested and would let things take their “natural course”. We know where that leads. But it was their choice. I have had to make my peace with that. This is not something everyone wants to embrace! So I understand that you get a response of “ what is dementia?”

On a brighter note, I laughed several times reading your post. For one thing, I think you’d have been an excellent doctor, an outlier to be sure!! I also enjoyed recognizing a thread running from The Boss and turning up here in your post. J11, for a couple of decades I saved a Rolling Stone magazine with the cover story ““Bruce Springsteen and the Secret of the World “ (Feb 1981). I loved it and took it to heart. He came to the exact conclusion you stated here:

Find something that you love doing and then find a way to be paid for it. This seems to be the recipe of life success