A Clarification...

Yesterday, I wrote about chronic diseases stemming from metabolic syndrome.  These included heart disease, high blood pressure, type 2 diabetes, Alzheimer’s disease, some cancers, etc.  I said that RFK Jr had taken a position on this that I thought was important.  However, this should not be taken as an endorsement of all things RFK Jr.  Even in the area of medicine and health, some of his ideas are, well, fringe, and I'm not on the same page with him.  I simply agree with him that our response to the diseases stemming from metabolic syndrome needs much more focus on prevention as opposed to medications.

An anecdote:  When I was 17, I worked in a shoe store not far from Hickory Hill, the Robert F. Kennedy estate.  At back-to-school time, Ethel would have their chauffeur (can't remember his name) load all the kids into their limousine and send them to our store for new shoes.  RFK Jr would have been about 12.  Robert and Ethel eventually had 11 children, two of whom had not yet been born.  I remember them all sitting in a row against the wall, waiting for Mort, my boss, to fit each one.  (Note: I may have worked at a store near where the Kennedy's lived, but we definitely lived on the other side of the railroad tracks from them.)

The first Alzheimer's survivor is out there. And the second. And the third...

As you know, I support the work of the Alzheimer’s Association.   They do wonderful things to support families in their terrible struggles with dementia, and, behind the governments of the US and China, they are the third largest sponsor of Alzheimer’s research in the world. 

That being said, I have been thinking recently about their fundraising hook, “The first survivor of Alzheimer’s is out there…”  Hey, I’m a survivor of Alzheimer’s disease, and I’m not the first one.  From 2015 through 2018, the evidence of my disease was as strong as it could be, but the symptoms are now apparently behind me.  So, I count myself as a survivor of the disease. 

I didn’t make up the “Dementia Toolkit” on my own.  It’s based on the experience of others who overcame the disease through lifestyle changes.  Others had similar experiences, such as those involved in the FINGER study and the subjects of Dr. Dean Ornish’s work.  In Beating the Dementia Monster, we discussed the success Dr. Dale Bredesen has had, although I’m skeptical of some features of his program outside of lifestyle changes.  So, I’m not alone.  We don’t know who that first survivor was, but he or she has been around for a while. 

What has me thinking about this is the book, Blind Spots.  I’ve been considering it along with what RFK Jr. has been saying about chronic diseases.  A way of looking at the practice of medicine is to identify an ailment, name it, and search for a medication that will cure it. 

For example, I remember when polio terrified parents, as many thousands of children succumbed to it.  I remember the rows of iron lungs working to keep so many four- and five-year-olds alive.  Today, I know a couple of people who are living in wheel chairs or are otherwise physically impaired due to having the disease in the 1950s.  The March of Dimes raised the money to do the research that led first to the Salk vaccine and then to the Sabine vaccine. Many lives were saved. 

But RFK Jr’s point is that, for the chronic diseases presently advancing in the culture, just inventing pills to fix things isn’t the right approach.  Most of the chronic diseases—heart disease, high blood pressure, type 2 diabetes, Alzheimer’s disease, some cancers, etc.—are a consequence of poor lifestyle choices.  We call Alzheimer’s disease “type 3 diabetes,” because the same factors that drive metabolic syndrome—leading to diseases like type 2 diabetes—also drive Alzheimer’s disease.  You may invent a pill or come up with an infusion to help control symptoms, but the disease itself is a consequence of lifestyle choices, and pharmaceutical treatments here are not cures.

After speaking with quite a few knowledgeable people, it appears to me that no one believes there will ever be an outright pharmaceutical cure for Alzheimer’s disease.  Instead, there will ultimately be a cocktail of medications that, coupled with appropriate regimens of exercise, diet, sleep, and social activity, will get us as close as possible to a “cure.” 

Regarding Blind Spots, Dr. Makary’s point is that the medical profession gets stuck on certain paradigms, and it is too slow to recognize it’s not on the best path.  My take is that, when all the focus is on coming up with a pharmaceutical solution, the best path forward—lifestyle change—is overlooked. 

Now, this ain’t easy.  I’ve had a number of people approach me for help with their issues on cognitive decline.  Usually, when someone is concerned enough about cognitive issues to seek help, they probably are actually dealing with disease, not the consequences of normal aging.  But the people who come to me are usually spouses of people with issues. 

Of course, the first thing I do is tell them I’m not a doctor, and I recommend specific specialists I trust. Nevertheless, I do explain my experience and suggest that, in addition to seeing a real doctor, they adjust their lifestyle.  But when I get to that part, they usually lose interest.  Get daily exercise?  Cut out desserts?  Stop eating processed foods?  For many people, these are non-starters. 

Every morning when I wake up, I can’t believe how wonderful my life became after I got control of my lifestyle.  Beyond that, the reason I get up is to share my experience with those who could benefit from it, even if not everyone is willing to listen.

"Blind Spots" by Dr. Marty Makary

Dr. Marty Makary's book, Blind Spots, was available September 17 of this year and now shows up as #14 on the NY Times non-fiction best sellers list.  The subtitle is, "When Medicine Gets It Wrong, and What It Means for Our Health."  I have skimmed it and am now reading it.  The book takes a rather critical view of the approach medicine has taken to a number of health issues, pointing out that incorrect ideas propagate in the medical community and are not challenged until many people have been hurt.

The book attracted my attention because I hoped it would address how medicine has focused on a pharmaceutical approach to Alzheimer's disease as opposed to taking lifestyle head on.  That's not outside of the scope of the book, but he doesn't really spend time there.  

In Beating the Dementia Monster, we mentioned that Dr. Dale Bredesen had encouraged post-menopausal women who had stopped taking hormone replacement therapy to resume it.  Makary has the same assertion.  Women were discouraged from taking it, after a study connected the therapy with an increased risk of breast cancer.

Makary cites this as a major fail of medical science.  He cites studies that failed to support the connection with cancer, and he says the benefits of the therapy far outweigh the risks.  He specifically cites some significant statistical evidence that women taking hormone replacement therapy have a very much reduced probability of developing Alzheimer's disease.

Makary cites other conditions he believes represent failures on modern medicine, including:

-- Promotion of nut allergies in children by preventing their early exposure to nuts

-- Abuse of antibiotics

-- Demonization of dietary cholesterol and red meat

-- Origins of the opioid crisis

and more.

Makary focuses on the phenomenon of "group think."  A chunk of my engineering career was taken up with accident investigation.  I investigated serious industrial accidents as well as nuclear facility events and accidents.  The goal was always to find the root cause, a cause that could be corrected to prevent recurrence.  And quite often, we identified group think as a cause.  In group think, a consensus on a process or solution to a problem arises in the group.  Being consensus grants a proposed process or solution special authority, and so bad ideas are not easily challenged.  When the idea arises in the medical community and propagates in the culture that peanut allergies can be prevented by keeping peanuts away from young children, we get an epidemic of peanut allergies.  Even though evidence arises to contradict this belief, it remains embedded in the thinking society in general and doctors in particular. 

When I bought the book, I was hoping for more focus on chronic diseases (like Alzheimer's disease).  He seems to have some thoughts there, but they don't come out so much in this book other than in hormone replacement therapy.

Robert F. Kennedy, Jr. has some serious thoughts on chronic diseases.  While I definitely don't want to get into any political discussion on this blog, I was impressed to hear the focus he wants to bring to chronic disease.  I heard him speak on the subject.  He wants to make changes to the food supply and otherwise discourage the lifestyle habits that lead to many chronic diseases.  Alzheimer's disease would, of course, be a prime target for such an effort.

My New Speculation on the Sundowning Phenomenon

In Beating the Dementia Monster, I commented on mild depressions I was experiencing in 2015, 2016, 2017, and perhaps later.  They would begin in late afternoon, but disappear in the later evening.  During my diagnosis, my doctors asked me a number of questions suggesting they were investigating my reports as sundowning.  They never concluded anything, but I'm convinced this was sundowning.

Originally, the depressive episodes occurred four or five times per week, but became less frequent when I began changing my exercise, diet, and other habits.  To my recollection, they did not decrease in intensity, but they became less frequent as I proceeded with implementing the Dementia Toolkit.  After six months, they occurred something like twice per week; and after a year, once every two or three weeks.  Or so I recall.  It seems that during 2017 they might occur once every couple of months.  At this point, it's been several years since I had an episode.

In Beating the Dementia Monster, we discussed the conventional medical hypothesis that changing shadows late in the day cause confusion among the elderly with dementia.  But I haven't seen this explained as proven fact, and, quite frankly, I reject it.  I said that during one of the worst periods of my experience, we traveled to Alaska during summer.  At 9 p.m., the sun was still high in the sky, and I didn't experience an obvious period of "changing shadows."  Nevertheless, I experienced the depressive episodes according to the same timing as back at home.  As near as I could tell, the experience in Alaska was identical to what I experienced at home.  I speculatively concluded that the timing of the episodes was more associated with my circadian rhythm than environmental factors. 

What may (or may not) support my speculative take on this is this article referred to me by my friend, Teale.  We've written several times about new methods for diagnosing Alzheimer's disease, including blood tests.  The article refers to some new research from the University of Surrey in the UK exploring some of these blood tests.  The tests, of course, look for proteins and other chemical biomarkers for Alzheimer's disease in the blood.  What the researchers were surprised to discover is that the biomarker concentrations varied with the circadian rhythm and were highest in the evening ... right when sundowning occurs.  So ... something we don't understand about Alzheimer's disease varies according to the circadian rhythm.  For some reason -- without a clear cause and effect relationship -- both chemical activity and depressive episodes vary together.

Now I am making this connection all by myself.  From what I can see, no one has tried to connect this phenomenon in blood tests with sundowning.  But for me, it makes a lot more sense than the changing shadows hypothesis. 

BTW, here's a picture I took on our trip to Alaska.  I kind of like it.

What's up with Alzheimer's research?

So I haven't posted for a while.  One of our children was married over in Seattle, and, as an elder in our church, I've had a lot to do there.  And then I sometimes have slow periods finding content I think you'd find interesting.

For those interested, I've given up on acupuncture for insomnia.  At least according to my Fitbit, I had some minor, transitory improvement in sleep quality, but I can't really say it did anything for my insomnia.  So I just continue to adapt to life the way it is.

But what’s been going on in the world of Alzheimer’s research?  Are there new drugs coming?  Any breakthroughs in understanding the disease?  Well, here are a few items of interest that I’ve noticed.  It’s certainly not complete, and the items are in no particular order.  Spoiler alert: there are no breakthroughs.  But these were interesting to me. 

Fosgonimeton, a drug with a history of safety, was expected to improve cognitive and daily functioning in adults with mild to moderate Alzheimer’s disease.  But it failed to meet its goals in a recent second phase of a three-phase clinical trial.  The drug was being developed by Athira Pharma.  It is not designed to remove amyloid plaques.  After all, removing amyloid plaques may not be the best approach to treating the disease anyway.  There were some positive improvements in some of the test subjects, so this drug may not be dead yet.

Alzamend Neuro and Massachusetts General Hospital are preparing to conduct a Phase 2 clinical trial of a candidate treatment code named AL001.  This is an oral therapy being developed for dementia related to Alzheimer’s disease.  It will use a new system for delivering lithium to the brain.  So far, pre-clinical studies and the Phase 1 trial have demonstrated its safety with a small group of test subjects … the main purpose of Phase 1 trials.  But I don’t see any claim that the earlier trials found any improvement in memory and cognition.

Amylyx Pharmaceuticals is testing an oral therapy code named AMX0035.  In a recent trial, the study drug reduced the levels of several biomarkers associated with Alzheimer’s disease.  A company press release stated, “The results from this exploratory analysis suggest that AMX0035 engages important pathways implicated in the [development] of Alzheimer’s disease and other neurodegenerative diseases.”  Despite these results, data from a Phase 2 trial showed that six months of oral treatment failed to slow cognitive decline compared with a placebo.

In a proof-of-concept clinical trial, treatment with a prospective pharmaceutical, CT1812, previously called Elayta, slowed the decline of cognitive function among adults with mild to moderate Alzheimer’s disease.  That’s according to results after about six months of treatment at trial sites in the U.S., Europe, and Australia.  In a company press release, Lisa Ricciardi, president and CEO of CT1812’s developer Cognition Therapeutics said, “The trial showed that after 182 days of treatment, [CT1812] demonstrated evidence of clinical improvements on cognition coupled with a favorable safety and tolerability profile.”  Ricciardi added that the findings “will inform dose selection and provide a foundation for advancing [the therapy] to the next stage of clinical development.”  Of course, a “proof of concept trial” comes even before a Phase 1 trial.  So this one has a long way to go.

As I found out when I was first diagnosed, donepezil (Aricept) can cause significant gastro-intestinal issues.  That’s why I stopped taking it.  This is a problem with this whole class of drugs, the acetylcholinesterase inhibitors.  Now, the FDA has approved the oral therapy Zunveyl (benzgalantamine), previously known as ALPHA-1062.  Zunveyl carries the acetylcholinesterase inhibitor galantamine through the digestive track and then into the blood stream before releasing it.  This bypasses the stomach issues.  According to Dr. Elaine Peskind, (with whom I am acquainted), an Alzheimer’s expert at the University of Washington School of Medicine in Seattle, approval of the drug “marks a meaningful step forward in improving the quality of life for those living with Alzheimer’s and their families.”

Administration of Montelukast oral film, an existing therapy being repurposed by Intelgenx to treat mild to moderate Alzheimer’s disease, led to significant improvements in patients’ cognition versus a placebo.  This was according to a report of a Phase 2 clinical trial.  The drug was approved years ago as a treatment for asthma, but it may have value in treating Alzheimer’s and Parkinson’s diseases.  But there was a confusion factor in the report summary: “[W]hen considered across all doses of [Montelukast], no benefit to general cognition was observed when compared to change under placebo.”  Go figure.

A New Drug on the Horizon?

Troriluzole.  I've never heard of it before.  But it just popped up on my radar as a new treatment candidate for Alzheimer's disease.  It's currently being investigated as a treatment for some forms of cerebellar ataxia (like mine?), obsessive-compulsive disorder, and some other neurological disorders.  It's a formulation of the existing drug riluzole that is used to treat ALS -- Lou Gehrig's disease.  The re-formulation is to increase its bioavailability.  

But suddenly, a study from Auburn University in Alabama, published in the Journal of Neurochemistry, indicates that it may treat underlying mechanisms in Alzheimer's disease ... in mice.  Mice again, but you have to start somewhere.  At least we already have a lot of experience with the riluzole from a safety standpoint.  And administration of the drug to genetically modified mice -- modified to produce a disease like Alzheimer's -- improved their memory and cognition.

It's probably a long way from the work with mice to an approved treatment.  But what's interesting about this investigation is that it may lead to better insight on how Alzheimer's actually works.  It's increasingly evident that removing amyloid plaques simply addresses symptoms, not the underlying disease.  But most of the drug strategies getting attention are about removing plaques.  And sometimes removing plaques doesn't even help.  So it may be that, not only do we get a new drug that will deal more directly with the underlying disease, but we will learn more about what the disease even is.  (Because we don't really know!)

Here's an article about the research.  But beyond what I've said here, the discussion gets pretty deep.

Whither the Acupuncture?

Back on August 10, we wrote that I had begun getting acupuncture treatments for my insomnia.  At the time, I had completed one treatment, and believed I had gotten some improvement.  Not that I didn't wake up in the middle of the night as in the past, but that first night my Fitbit recorded significant improvement in sleep quality.  So I thought it was worth continuing to see what would happen.  (Some of you suggested this was a placebo effect, and -- I don't know -- maybe you're right.)  The research I cited in my August 10 post used six treatments as a benchmark for evaluation.  I thought that was a good goal for me.

Except that I need to be good at counting to make sure I get all six...

As of last Friday, I thought I had completed the six treatment goal.  Aside from the initial boost in sleep quality, I didn't feel that my sleep had improved.  I still woke up in the middle of the night, and my sleep scores were back to being pretty bad.  So I said that last Friday's treatment would be my last.  Except that was only five treatments, not six.  (I don't count good.)

My pattern is to get to sleep relatively easily, but then wake up at 1 or 2 a.m.  When I wake up, I REALLY wake up, and in an unpleasant way.  It's painful even just to lie there.  So, I would get up and take care of a few things, but I had always been able to go back to bed and get back to seep after being up for one and a half hours.  This might yield six and a half hours of sleep.  Not ideal, but I can live on that.  But for the past few months, getting back to sleep has been nearly impossible.  I would feel unwell during the day, and I thought I could just nap after noon.  Aside from a schedule that didn't accommodate naps well, I usually couldn't even get to sleep for the nap.  If I could get to sleep, it would be only for 15 minutes or so -- not making up for what I lost the night before.

After cancelling my subsequent appointments, it occurred to me that, after starting the acupuncture, I have recently actually been getting back to sleep at about 4 a.m. and been sleeping OK after that.  Waking up last night was quite unpleasant, but I went back to bed after an hour and a half, and my Fitbit says I actually got seven hours with a (for me) good sleep quality score.  This is a more sustained improvement -- it's been a long time since I've seen that.  So maybe I was premature on cancelling my appointments, and I should reschedule.  Stay tuned.