Medical news today, not great

M1

I'm not good at posting links, but the results of a monoclonal antibody trial (donanemab) in early Alz was published in today's New England Journal of Medicine, and an editorial.  Like most trials so far, this showed statistical improvement, but it did not translate into any practical results.  Takeaways:

We're talking VERY early disease, requiring meticulous diagnosis (which is not being done in most cases).  Only 1 in 10 folks screened for the trial actually qualified for it.  Point of editorial is that as treatments come along, careful early screening and diagnosis is going to be more and more important, and it's not being done now.  It's not been worth it and probably still isn't, yet.

The treatment involved monthly IV infusions over 18 months, 257 participants (think of doing that with your loved one).  Treatment vs. placebo, there was 25-30% less decline in function as measured on a standardized rating scale, but in reality, this was barely significant statistically and not significant clinically:  "amounted to a 3-point difference on a scale ranging from 0-144,  and the clinically relevant secondary outcomes of dementia severity, cognition, and functional abilities all failed to show treatment effects."  Takeaway:  amyloid proteins are involved, but we've still got a long, long way to go before we have anything useful.  Would this be worth monthly, costly infusions?  I doubt it.

Another takeaway:  those populations most affected by Alz are still underrepresented in the research, and as treatments come on line, the access discrepancies are likely to worsen unless we're careful.

Wish it were better news.

sandwichone123

This is a really good, understandable report. Thank you.

Lane Simonian

This is indeed very good analysis.

In other anti-amyloid drug trials (albeit different forms of amyloid--amyloid oligomers rather than plaques), the drugs had almost no effect on non-ApoE4 carriers and modestly slowed down the progression of the disease in carriers.

https://pubmed.ncbi.nlm.nih.gov/29199323/

https://www.alzforum.org/news/conference-coverage/second-look-ban2401-data-still-positive-despite-snafu

Amyloid does play a role in Alzheimer's disease but apparently only in those with one or two copies of the ApoE4 gene.  The likely reason for this is that people with this gene or genes have more oxidative stress and more amyloid than those without the gene.  In addition, amyloid is likely a secondary trigger (and again only in ApoE carriers).  Other factors such as a diet high in sugar and other carbohydrates, psychological stress, or exposure to environmental toxins like are primary triggers that lead to amyloid and oxidative stress in the first place.