Still Me; Accepting Alzheimer's Without Losing Yourself, by Rebecca S. Chopp, PhD

Back in October, I wrote about Dr. Rebecca Chopp who was writing a book on her experience with an Alzheimer's diagnosis.  I had stumbled on an interview with her on NPR, and it was evident that she had made some lifestyle changes and was at least enjoying some relief from her descent into dementia.  Her book was not yet out, but I did write to Dr. Chopp to remark on the similarities of our stories.  She replied enthusiastically, noting that she had read Beating the Dementia Monster, and was encouraged by my story.

Her book was published in May, and I have now read it.  It was very much worth my time.  It begins with her initial diagnosis and, like me, a prediction of only a few years to live.  Unlike me, her first diagnosing neurologist had a terrible "bedside manner" and offered no hope.  At least my physicians were sympathetic and suggested lifestyle changes, although none of them said the changes would actually do much good.

In Dr. Chopp's case, she found medical help that steered her to the necessary changes, and she tells about how all of that went for her.  Not surprisingly, the necessary changes mirrored the Dementia Toolkit of Beating the Dementia Monster.  At the end, she comments on her last visit with her neurologist, five years after her diagnosis, who said her symptoms had not progressed very much, and her prognosis was better than she ever thought it could be.  I am not surprised.

The book ends quite beautifully with a poem, the lyrics to a song, written for her by Murray Decock.  Decock is both a composer and academic.  If you finish the book, you should definitely go to the YouTube video performance of the song.  It is quite moving and does a masterful job of concluding Dr. Chopp's story.

While Dr. Chopp's book tells a similar story to mine, it's really quite different.  Both of us wanted to convey hope with what we wrote, but we are different people, and we are writing to different audiences.  She is a woman of letters, having presided as president and provost over several universities.  I am an engineer and a student of both physics and biology.  Her book is a memoir that focuses much more on her personal experience, while mine delves into the science about why we would both get better if we did certain things.

My sense is that Dr. Chopp's story will appeal primarily to her peers in the arts and the academy.  And that's good.  I am the oldest of nine children, several of whom are faculty in first tier universities.  Other family graduated from first tier universities.  Amy and I live in walking distance to both a major national laboratory and a branch campus of Washington State University.  So my family and our neighborhood are populated by people who would appreciate her story.

On the other hand, the friends that I trust most have a bachelor's degree in engineering or they never attended college at all.  When I wrote, these were the people I most hoped would read my book and benefit from it.

Whither Alzheimer's Research?

On June 10, the FDA's advisory panel voted unanimously to recommend approval of Eli Lilly's new monoclonal antibody treatment, donanemab.  This is the same panel where some members quit when the body recommended approval of aducanumab.  While there was some rejoicing over this latest action, much of the reaction was actually muted, as you can see in this article in Nature and this one from the AP. 

So aducanumab (marketed as Aduhelm) has been eclipsed by lecanemab (marketed as Leqembi).  Will donanemab, in turn, eclipse lecanemab?  I read that the two may be better suited to different patients, so probably not.  But all of the monoclonal antibodies (Alzheimer's drugs ending in "mab") are known to cause brain swelling and microhemorrhaging.  As we noted before, a very few subjects died during clinical trials for lecanemab.  Also, according to the AP article, from donanemab.  And, of course, they are all very expensive.

Approval by the advisory panel is not approval by the FDA, but FDA approval of donanemab is likely to follow soon.  We don't yet know what commercial name it will be sold under, nor do we know the price.  But we do know that none of these "mabs" cures Alzheimer's disease, suggesting they are not attacking the disease itself.  Rather, they are alleviating symptoms.

So what does this say about the state of affairs in Alzheimer's research?  

When I was first diagnosed in 2015, there was great optimism about where research was going.  I read an article in a very popular magazine by a doctor who said they should just release one of the prospective treatments without completing the clinical trials, because the treatment was so promising, and people were dying from Alzheimer's anyway.  They didn't name the treatment, but I later concluded it was probably aducanumab.  But when aducanumab appeared to fail dramatically in its disastrous third phase clinical trial, it sent shock waves through the Alzheimer's disease scientific and medical community.  I was surprised by the shock, because I was already a skeptic, and I didn't realize how much hope had been invested in aducanumab.

People are now more wary of premature enthusiasm about new breakthroughs.

And wary they should be.  A long time ago, funding for research assumed that the hope for a cure lay in the amyloid hypothesis.  So attention -- and scientific assumptions -- followed the money.  People with Alzheimer's disease have these amyloid plaques in their brains, so if we remove the plaques, they'll get better.  Right?  ... Right?  

That idea hasn't worked out very well.  As we said in Beating the Dementia Monster, the plaques may actually just be the body's mechanism for fighting the real culprit -- whatever that is.  So the plaques are probably symptoms rather than the disease itself.  And the spectacular success researchers have had in removing the plaques hasn't caused people to be cured.  The progress of the disease may be slowed, but no one gets better by using these treatments.

Then what is the real culprit?  The bacteria that causes gum disease?  The virus that causes shingles?  There is evidence for hypotheses like these, but most of the money has flowed toward dealing with amyloid plaques.  There's work going on with these and other ideas, but there's still a tug-of-war for money.

I was prompted to write about this after reading this article in Vox.  The article didn't say anything we haven't discussed here, but it puts the current disarray in the research world into a more public forum. 

I am a bad blogger

Yes, it's true.  Mainly because I'm very slow and inconsistent in responding to comments.  So I want to kind of catch up on recent ones.

First, I get many very positive comments, both by postings on the blog and via email.  This is so gratifying to me.  After experiencing the amazing turnaround in my condition, my reason for getting up each day is to encourage others who are confronting, or may confront, the same monster.  Well, it's one of the reasons.  After selling over 11,000 copies of Beating the Dementia Monster, and unexpectedly encountering people who have stumbled on it and read it, I know my efforts have made a difference in some lives.

Anyway, what follows are my responses to comments over the past several months that seemed to anticipate that I would respond.  Note that the system doesn't always tell me who actually posted a comment, and it just identifies them as "Unknown."

Now Espresso fights Alzheimer’s disease? - August 15, 2023

Comment from “Unknown”: I reached out to the researcher - Question: "I currently drink coffee regularly, but espresso only on occasion. I'm trying to decide if I should make a change.  Did your research find that espresso is beneficial above regular coffee? Or is drinking coffee also a good move?" 

The researcher’s answer to Unknown: "We made a in-vitro research using only espresso.  We still don't know to what extent our findings are confirmed in vivo.  However, the molecules contained in the regular coffee are not so different in terms of type and amount, from that of espresso."

My response: I appreciate you investigating this further and sharing your findings!

Sushi for Brain Health? - January 15, 2024  

Comment from “Unknown”: I will be interested to hear how it goes. Also, I think I understand you as saying that the paste form of wasabi is ineffective.  Can you please clarify?  I'm not sure what other forms are available.  Thank you for your blog.  I find it both informative and inspiring.  Joan 

My response: Joan, sorry to be so slow replying to your comment!  I wasn't trying to say that the paste form is ineffective, rather that product sold as wasabi is often more horseradish than actual wasabi.  I suspect that the wasabi I've bought on Amazon was actually more horseradish.  There are web sites claiming to sell pure wasabi, but it can be pricey. 

Why the MIND diet excludes cheese, butter, and margarine -- now we may know. - May 28, 2024 

Comment from “Unknown”: I'm curious to know why stick margarine is specifically mentioned; does that mean other types of margarine (tub margarine, I suppose) are less likely to contribute to the kinds of detrimental effects found in the study?  And if so, what's different about them?  And thank you for this blog.  I follow it avidly. 

My response: Thanks so much for your kind words. In "Diet for the Mind," Dr. Morris said that stick (or block) margarine is more hydrogenated and contains more transfats.  She said that tub margarine is much better, but she preferred olive oil.  I stick with olive oil. 

Comment from Sui Generis: So where does this leave us with eggs? I've been eating two eggs every day for breakfast.  The sample meal planner at https://www.healthline.com/nutrition/mind-diet even includes them.  The articles you referenced don't mention eggs, but neither do they mention cheese. 

My response: Sui, from what I read, it seems that eggs have been completely let off the hook.  In "Diet for the Mind," Dr. Morris says they got a bad rap, and they're full of important nutrients.  The only reservations about them I've heard recently is that you shouldn't eat too many (more than two a day), because they haven't been studied enough.   I don't have any reservations about eating eggs, even more than two. 

Regarding cheese, Dr. Morris was very critical, notably regarding mozzarella, since Americans eat so much of it.  In the US, we put a lot more cheese on pizza than other countries, so pizza consumption seems to be implicated in Alzheimer's disease here.  It has a lot of saturated fat, which she believed is the culprit.  After seeing her own research findings, she cut her consumption of cheese way back. 

Genes that control dementia in the face of advancing Alzheimer's disease - June 14, 2024 

Comment from “Unknown”: Might therapies be developed to help more people "express" those protective genes? Do we all have the genes, even though they are only "expressed" in some people? That sounds like an intriguing possibility to me. 

My response: I brought up “expressing” genes because the research article used the term, and I like to differentiate genes from the proteins that result from them.  Contrary to what a lot of people believe, genes don’t actually do anything.  They are simply the blueprints for the proteins that will do something. So, mRNA molecules read the genes and take the information to the the ribosomes.  The ribosome uses the information the mRNA read from the gene to assemble a chain of amino acids and, from the chain, form a protein molecule.  

You have the genes you were born with, and different people have different variations of many of them.  That’s why we look different from each other.  Identical twins have the same genes, and so they look the same as each other. 

But every gene exists in every cell of the body, even in cells where this gene or that gene will never be used.   So, genes are expressed selectively.   If a cell will be used to color your eyes, the genes governing eye color will be expressed as special proteins in that cell, but not in, say, a bone cell.  Expression of genes is controlled by “gene regulation networks.” 

This is a lot more than you asked for! 

Regarding your question, the point is that the important variable is which genes you drew in the lottery, rather than when genes will or won’t be expressed.   But … for people who drew the better genes, might there be therapies out there that would better exploit them by expressing them more or somehow differently?   That’s a good question.  But not one I’m qualified to answer. Nor have I seen anyone address it.

Genes that control dementia in the face of advancing Alzheimer's disease

We know from a variety of studies (and my experience!) that cognitive decline may be suppressed even when Alzheimer's disease advances.  The classic example is the Nun Study, in which a few women were found on autopsy to have evidence of advanced Alzheimer's disease but who did not display evidence of dementia before they died.  What was different about these people?  Inquiring minds want to know.

I came across an interesting study published in the journal Acta Neuropathologica Communications that found genetic makeup can play a role, especially with genes involved in immune response.  Researchers  from the Netherlands studied the brains of a sample of deceased people where it could be determined that they did or did not show evidence of dementia before they died.  Also, it could be determined whether they did or did not have Alzheimer's disease.  The presence of amyloid plaques, certain tau proteins, and atrophy gave evidence of Alzheimer's pathology.  They compared these parameters to the genetic makeup of these people.  The article was entitled, "Gene-expression profiling of individuals resilient to Alzheimer's disease reveals higher expression of genes related to metallothionein and mitochondrial processes and no changes in the unfolded protein response."  (I'm sure there's a longer title somewhere, but I haven't seen it yet.)

Long story short, there were people in the study with evidence of both Alzheimer's disease and dementia, a much smaller number of people without dementia but with evidence of Alzheimer's disease, and a number of people with evidence of neither Alzheimer's nor dementia.  There were certain special genes "expressed" in the population with Alzheimer's disease who did not have dementia that were not expressed in the other populations.  ("Expressed" means they were activated for use in producing specific proteins.)  These genes were largely associated with the immune response.  There was also correlation with the related proteins to how the brain reacts to metals entering the brain and in the processing of energy.

Note that, in Alzheimer's disease, it's metals in the brain that may oxidize and cause damage, which is why we eat blueberries.  Also, PET scans used to diagnose Alzheimer's disease are looking at how glucose is processed in the brain for energy.  There is a progressive breakdown in the metabolism of glucose in Alzheimer's disease.  So proteins from these genes, either directly or indirectly, appear to be suppressing the way in which Alzheimer's disease is promoting oxidation and interfering with metabolism of glucose.

I am certain that you do not want to read the research report.  However, if you're interested, here's an article from Science Direct that breaks it down for you in a way that's easier to understand.  But the article gets into something dearer to my heart that's not addressed directly in the research paper.  That is the population of people without these special genes and have Alzheimer's disease, but do not have dementia.  Since I was developing dementia, and my MRIs had the biomarkers for Alzheimer's disease, I surmise that I am one of these.  With regard to this population, the authors of the magazine article echo what we said in Beating the Dementia Monster -- lifestyle changes are the key to turning the disease around.

A deep dive on brain health and dementia

I'm always on the lookout for new articles and, hopefully, new insights on brain health.  Recently, I came across an interview with Dr. Wendy Suzuki, Dean of the NYU College of Arts and Sciences.  Dr. Suzuki is a neuroscientist and the author of the book, Healthy Brain, Happy Life: A Personal Program to Activate Your Brain and Do Everything Better.  She has done important research on neuroplasticity; how the brain sort of "morphs" in response to various changes in living environment and other demands on the brain.  (This occurs as neurons constantly disconnect from one another and then reconnect with other neurons to form new pathways for information inside the brain.)  Since 2018, she has focused heavily on the role of physical exercise, especially aerobic exercise, on brain health.

So, while on the treadmill at the gym, I watched this hour-and-a-half interview with Dr. Suzuki on Steven Bartlett's popular YouTube podcast, The Diary of a CEO.  Now, except for the latter part when she discusses her faith life, there isn't much information that we didn't talk about in Beating the Dementia Monster.  She goes through most of what I've called "the dementia toolkit."  But she is quite expressive and entertaining, so it was worth the time I spent watching.  For example, she shocks Bartlett when she produces an actual human brain and has him hold it.

If you're looking for an enjoyable discussion of where neuroscience is today with respect to the lifestyle choices we make and our vulnerability to Alzheimer's disease and other brain diseases, you should take a look here.  Or maybe get her book.