It's here -- a consumer-level blood test to measure Alzheimer's disease risk

We have been waiting for some time for a simple blood test for Alzheimer's disease.  And now there is one.  It's said to measure disease risk ten years before first symptoms, and you don't even need an order from your doctor to get it.

The test is being offered by Quest Diagnostics, and it costs about $400.  It's called A-D Detect.  While it's sort of an over-the-counter consumer product, it's not quite so simple.

You don't just get it done at your local pharmacy.  First, your application for the test needs to be evaluated by Quest's medical staff, and they'll figure out if it's appropriate for you.  Then you'll need to make an appointment at one of Quest's 2,100 test sites.  (The nearest site to me is 62 miles away in Yakima.). So you actually do need an order, just not from your own physician.

The test measures the ratio of two types of amyloid in your blood, AB42 and AB40.  A lower ratio of AB42 to AB40 indicates a higher risk of Alzheimer's disease.  They say that this is not measuring the presence of the disease, but rather your risk for developing it.

So why would you take this test?  To find out whether you should consider Leqembi or one of the other new monoclonal antibody treatments.  If you're going to be spending that much money on a treatment (~$24,000/year), you want to know it's probably treating the actual cause of your memory loss.  Of course, it also might tell you to start implementing The Dementia Toolkit of Beating the Dementia Monster! 

Where are Alzheimer's disease rates highest in the US?

The Alzheimer's Association International Conference 2023 was held (again) in Amsterdam and ran from July 16-20.  You may recall that it was entirely on line in 2020, and I attended the whole thing for free.  But this year, I'd have had to pay for the same level of access.  So I picked off interesting information from news releases and stories. 

The value of attending the conference is finding out first hand about the most exciting recent breakthroughs in Alzheimer' research from around the world.  The headline for the conference this year was the ongoing success in trials of donanemab, a new generation monoclonal antibody.  Apparently phase 3 trials have gone well, and FDA approval may be on the horizon. 

We've been writing about donanemab since 2019.  But something else I saw that was interesting was a breakdown of which localities in the United States have the highest rates of Alzheimer's disease.  Which will lead to a question of why the rate in some region might be higher than in another.  The research was published in the journal, Alzheimer's and Dementia; Journal of the Alzheimer's Association.

First, the states with the highest rates of people over the age of 65 living with Alzheimer's disease were Maryland, New York, and Mississippi.  Then, to break things down further, the counties with the highest rates were Miami-Dade County in Florida, Baltimore city in Maryland, and Bronx County in New York.  In each of these, about 16.6 percent of senior residents had the disease.  The next highest was Prince George’s County, Maryland, with 16.1 percent.

What was important here is that the locations with the highest rates had minority populations.  This points to the fact that we need a population of study subjects that has a much broader representation of the general population.  The current population is mostly white baby-boomers.

That insomnia cure...

So my brother reminds me that I need to update you on my experiment with sleep restriction cognitive behavior therapy for insomnia.  I last posted about it on July 9, but I've been slow with followup reports on its progress.  Long story short, it hasn't been the silver bullet I hoped for.

They warn you not to try it on your own.  You should have a coach, which I believe is necessary to maintain discipline in the process.  You will recall that the process is quite unpleasant.  But, then, they also point out that there are very few sleep coaches out there, and I didn't find one locally.  

Would things have gone better if I'd worked under the supervision of a coach?  Probably. Should I give it another shot?  Maybe, but not now.

Early on in the process, I believed that it was going reasonably well, and I felt I had some latitude with the protocol.  I had been trying to go to bed at midnight and wake up naturally at 5 a.m. for a week, but I couldn't really keep that up.  And I wasn't able to sleep all the way to 5.  So I was getting about four and a half hours of sleep a night, and the protocol forbids naps.

I decided to call it good enough for the first week of the protocol, and so moved my bed time to 11.  That kind of worked out OK, and I would sometimes get a reasonably continuous five or six hours.  I was supposed to do that for a whole week, but I shifted to a 10 o'clock bed time in less than a week.  And I actually protracted things by going off and on the protocol a time or two due to circumstances.

I did hit a point where I thought I had made a lot of progress, but then we had a trip to the East Coast ... three time zones away.  If that wasn't bad enough, Amy and I both managed to get covid on the trip, causing further disruption in my sleep schedule.

The whole concept behind cognitive behavior therapy for insomnia is to teach your brain habits about when to go to sleep and when to wake up.  If your schedule shifts three hours two times in one week, well that confuses the training.  

I may have mentioned before that when I got covid during the summer of 2022, it actually worked out to my benefit.  It was a very mild case (for me ... not so much for Amy), but it caused me to have three nights in a row of uninterrupted sleep.  I woke up each morning feeling great, and I only dealt with a mild fever the three afternoons. 

So this time, when Amy got it (probably in an airport), and it was clear I'd be getting it too, I thought I'd have a replay of 2022.  Well, not quite.  While it was still a relatively mild case, it was very disruptive to my sleep, especially since it fell right into the time when I was trying to adjust for the time zone changes.

I'm still trying to stabilize my sleep schedule from our trip.  My neurologist suggested a higher dose of melatonin, which I've been trying.  In Beating the Dementia Monster, we noted that both my sleep doctor and the well known sleep researcher, Dr. Matthew Walker, consider melatonin to be a placebo with respect to insomnia.  My extensive experimentation with it seemed to confirm that.  But using the higher dose recommended by my neurologist seems to help a little on some nights.

We have a trip to visit family in Hawaii later this month, and that's three time zones in the other direction.  We'll be there two weeks before returning home.  So how's that going to work out?

I'm hoping that when I'm over the repercussions of our trip and the covid infection that I'll get back to some reasonable sleep schedule, even if it involves two or three periods of sleep each night.  If that happens and remains stable for a while, maybe I'll try the sleep restriction therapy again.  Maybe.

Now espresso fights Alzheimer's disease?

Maybe you saw it in the news, but a new study found that chemical compounds in espresso (including caffeine) interfere with the formation of tau protein tangles, and may therefore protect against Alzheimer's disease.  Speaking as a major coffee lover, this sounds too good to be true.  (But we can at least pretend to be sure it is.)

On July 19, the research was published by the American Chemical Society in their journal Agricultural and Food Chemistry.  Long story short, researchers from the University of Verona in Italy collected commercial samples of espresso and extracted certain chemicals from them, including the caffeine.  In the laboratory, they then exposed brain tissue samples to the chemicals and found that tau proteins formed shorter fibrils, and did not agglomerate as readily.  This apparently inhibited their ability to spread the disease throughout the brain.

Okay, to understand this, we need to go back to Beating the Dementia Monster and review some of the things we said there.  We discussed tau tangles -- clumps of tau protein that aggregated when defective tau protein lost its strength and couldn't hold the microtubules together.  The microtubules are like the skeleton of the brain cell.  In Alzheimer's disease, they lose their strength and collapse into a "tau tangle."  The brain cell then dies.  Alois Alzheimer saw these tangles, along with amyloid plaques, in the brain of his deceased patient, Auguste Deter.

We also said that Alzheimer's disease can proceed for as many as 15 years before the first symptoms appear.  Apparently, at about 15 years, there is a "tipping point."  At the tipping point, defective tau protein is abruptly seeded throughout the brain, spreading the disease and creating disruptions in cognition and memory.  The researchers concluded that the shorter fibrils would not spread through the brain, and the espresso might stop the disease from advancing.

At least that's what happens in a petri dish.  Does that also happen in the human brain?  As usual, they tell us, "More research is necessary." 

I'm not waiting for more research.  I'm going to continue consuming my coffee.  Unfortunately, the caffeine also aggravates my insomnia, primarily through nocturia.  According to my urologist, the caffeine irritates the bladder at night creating a sensation of needing to void.  If I'm off caffeine, I'll get up 2 or 3 times per night.  If I've had too much, even several days previously, I could be up more than 5 times.

Integrity issues in biologic research take down Stanford president

A year ago, we wrote about a scandal in which a researcher had fraudulently "photoshopped" some images used in research that misdirected some Alzheimer's research for perhaps a decade.  But, as it turns out, this was not an isolated situation.  Apparently quite a few research papers have been based on inappropriately altered images, and amateur detectives have been out finding them.  At least some of them.

This week, Stanford President Marc Tessier-Lavigne resigned due to questions about some of his published research, research in which some images had been inappropriately manipulated.  Tessier-Lavigne was a neurologist known for research in Alzheimer's disease, although image manipulation does not appear to have been involved in that research.

For me, what stands out here is damage to the public perception of the legitimacy of scientific research.  Especially after concerns about politicized covid information during the pandemic, my sense is that public trust has fallen dramatically.

So how's the insomnia cure going?

It's early to tell for sure, but the sleep restriction cognitive behavior therapy I've been trying does seem to be helping.  I am usually able to sleep the whole night through with 4 or 5 awakenings.  These are usually fairly short.  But I"m still often getting less than five hours a night, and naps aren't permitted.  But I do feel well about how things are going.

They say you shouldn't try this on your own; you should be supervised by a therapist.  Then they say good luck finding a therapist.  There aren't many of them.  So I'm doing it on my own.

I have graduated from phase 1 to phase 2.  Phase 1 had me going to bed at midnight even though I was unable to sleep beyond 5 a.m.  I'd been going to bed at 8:30 or 9 to find time during the night to get more sleep.  But I've found that, in the end, I get no more sleep by going to be so early.

The first week of going to bed at midnight (phase 1) was just awful, but I was amazed on night 6 when I actually stopped waking up at 2 or 3.  So after a week in phase 1, I rolled my bed time back to 11.  (My goal is to form a habit of going to bed at 10 and waking up at 5.  This seems doable.)  I'm still getting up earlier than I would like, but only once have I awakened around 3 and been unable to get back to sleep.  

I'm using my Fitbit along with the CBT-i Coach app to track my sleep.  The app creates a nice graph to show my progress ... or lack thereof.  

I'm not ready to graduate to phase 3.  I'd like at least a full week of sleeping through the night and awakening at 5 or later.  (Too often I'm fully awake at about 4:30 or so.)  Then I think I can roll my bed time back to 10.  The concept is that I'm creating a habit of sleeping to 5 regardless of bed time.  And because I was so sleep-deprived when I went to bed in phase 1, I seem to have broke the habit of awakening at 2 every night.  

So why am I having this problem when I'd been able to sleep nicely throughout most of my life?  According to Dr. Matthew Walker in his book Why We Sleep, the control center for our sleep is atrophying as we age and becoming more easily confused.  With neurodegnerative diseases, like Alzheimer's disease, this atrophy is accelerated.  So people in memory care are walking the halls all night.  The double-whammy is that poor sleep accelerates Alzheimer's disease.

I am optimistic about this.  Maybe I'm just getting used to surviving on 5 hours of sleep, but I feel well enough during the day, and I seem to be fully functional.  I look forward to feeling comfortable about rolling bed time back to 10. 

Can gut bacteria tell if Alzheimer's is developing?

One of the most amazing features of the human body is the gut-brain axis.  As we discussed last summer, microorganisms in the intestines have a signaling network with the brain such that the microorganisms exercise a significant level of control over what happens in the brain.  Bizarre, I know.  Nevertheless, good gut health contributes to good neurologic health.

Doctors often refer to "gut flora," meaning gut plants.  This hearkens back to the 1950s, in my late elementary school days, when the biological sciences were trying hard to sort all life as either plant or animal.  And they were trying hard to force fit bacteria into the plant kingdom.  That didn't work out very well.  It turns out that bacteria are more different from plants than plants are from animals.

And so more sophisticated folks will refer to "gut bacteria."  But that's not quite right either.  Many of the microorganisms in your gut are archaea.  Archaea are often referred to as bacteria, partly because, like bacteria, their cells have no nuclei.  They are the organisms that can live under extreme conditions, such as near volcanic vents on the sea floor.  They stain the glaciers on Mount Rainier pink, they allow goats to digest cellulose, and they give the hot water pools in Yellowstone their beautiful colors.  But there are ways in which they are significantly more different from bacteria than plants are from animals.

So we will refer to the gut microbiome and skip worrying about whether their citizens are plants, animals, bacteria, or archaea.  

Now since the gut microbiome plays such an important role in how the brain functions, it may also play a role in how Alzheimer's disease develops.  Therefore, logic says that you should be able to see the development of Alzheimer's disease somehow reflected in the gut microbiome.  Can you?  Maybe so.  

There was a new study published in the June 14, 2023 edition of the journal Science Translational Medicine, "Gut microbiome composition may be an indicator of preclinical Alzheimer’s disease."  As indicated in the title, the research explored the idea that Alzheimer's disease might be detected by analyzing changes in the gut microbiome during the preclinical phase of the disease.  This is before any symptoms develop.

The researchers studied 164 cognitively normal people, 49 of whom had evidence of preclinical Alzheimer's disease.  In other words, the 49 passed cognitive tests OK, but they had other evidence that the disease had already begun.  As we said in Beating the Dementia Monster, the preclinical stage normally lasts about 15 years, only ending when the first symptoms appear.  Usually it is simply undetected during that stage. 

So what did the research find?  "The gut microbiomes of people with preclinical Alzheimer's disease (indicated by altered brain amyloid and tau proteins) had a different composition from that of healthy individuals."  This means that examining fecal matter may turn out to be a less invasive method for diagnosing Alzheimer's disease than, say, the spinal tap that I underwent. 

On the other hand, if the blood tests we've been anticipating turn out to be as reliable as they appear, they may end up being the preferred diagnostic tool.  The gut microbiome researchers compared their approach to the spinal tap rather than the blood test.

Aside from perhaps using changes in your gut microbiome to diagnose Alzheimer's disease, some believe that supporting good gut health supports good brain health.  That may or may not be true, but I still do things thought to support the gut microbiome.  I eat yogurt (without all the sugar), fermented foods like kimchi, and fiber supplements.

This idea of resisting Alzheimer's disease by caring for your gut underscores something we've said before: this is an incredibly complex disease, and we just don't understand it well at all.