On "misremembering"

My classmate Mike in Virginia sent me this article from the Washington Post, "Why some misremembering might show your memory is functioning properly."  It's not about Alzheimer's disease or dementia, but it's still a very fascinating review of some things we're learning about how the brain works, written by a researcher in neuroscience.  

What initially caught my attention in the article was that it began with the work of  Daniel Kahneman and Amos Tversky.  Their partnership was the subject of the book The Undoing Project by one of my favorite authors, Michael Lewis.  My son got me this book for Christmas a couple of years ago, and I loved it.  It followed the careers of the two pioneering psychologists through their research years, through the breakup of their partnership, and to the death of Tversky from cancer.  Both would have received the Nobel Prize, except the recipient must be living.  So Kahneman accepted it for them both.  If you follow this stuff, you'll know that they came up with the concept of "heuristics" which now governs many statistical processes that we engage in.  This includes methods to detect viruses in your email.

If you're interested in the topic of the WaPo article, you should read it.  The upshot of it is that your brain is constantly assessing the meaning of inputs of varying quality from a myriad of sources.  For example, your ability to quickly assess the speed of a moving object that may not be in the center of your vision.  How clearly is your eye, working with your brain, able to discern it?  Is it in focus?  Then the registers in the parts of your brain containing your working memory can get filled up and make cognitive activities difficult.  This is easier to understand if you know how dependent your computer's processing ability is on its own memory.

The assumption in the 1960s, when Kahneman and Tversky were working together, was that there are a lot of deficiencies in how the brain works.  That's why people make mistakes.  One thing they studied was why military pilots made errors and crashed airplanes.  Some of their techniques improved pilot performance.  And they had other amazing insights regarding how people assess situations and make decisions.

However, the author of the article (who is working in this field) refers to newer research showing that the brain does an incredible job with the resources it has.  For example, it won't use up valuable space in working memory with unnecessary details about a topic, when that space could be used for more important information. 

ALZForum comes out tomorrow morning.  I'll see if there's anything interesting there.

People who had cataract surgery have a lower incidence of dementia

I just got my regular newsletter from the University of Washington's Alzheimer's Disease Research Center with a surprising research finding.  People who had cataract surgery had a 30% lower risk of developing dementia.  Obvious question: why would that be?

The findings come from the Adult Changes in Thought Study that's been going on since 1994.  The study tracks thousands of older people known not to have dementia and follows them until they do develop dementia.  Obviously many never will, but they'd like to know about the lifestyle differences between those who do and don't develop dementia.

So why would people have a lower incidence of dementia if they had cataract surgery?  An article in Science Daily provided some speculation.  The article noted that the research report did not provide any answers, but some people have proposed some.

One idea is that, after cataract surgery, people get higher quality sensory input, and that's somehow good for brain health.  

Another idea is that after cataract surgery people are getting more blue light.  Cataracts cause the light getting to the retina to be more yellow, filtering out blue light.  Blue light may stimulate some cells in the eye associated with cognition.  The new, bluer light might stimulate those cells somehow.  This affects the sleep cycle that depends on blue light to tell the body that it's day.  So it might promote better regulation of the circadian rhythm and better sleep.  If you read Beating the Dementia Monster, you know that sleep is extremely important in how Alzheimer's disease does or does not develop.  

So get outside during the day when there's lots of blue in the sky and blue in the light.  You're teaching your brain what time of the day is daylight.  But don't expose yourself to light containing a lot of blue in the evening, such as cool fluorescent and LED light.  This goes double for light from computer and phone screens.  It's been super-juiced with blue.  (I've calibrated the colors on my computer screens to be warmer -- more yellow, less blue.)

I'll add my own speculation which I think is consistent with these ideas.  We have associated hearing loss with dementia, likely because hearing loss interferes with communication with other people.  As we said in Beating the Dementia Monster, social connection is very important to brain health.  Impairing social connection, such as through hearing loss, raises the risk of Alzheimer's disease.  Maybe the same thing applies here -- untreated cataracts interfere with social connection.

Another thing we noted in Beating the Dementia Monster is a correlation between glaucoma and dementia.  People are often diagnosed with glaucoma very near the time they are diagnosed with cognitive impairment.  In my case, only a few months separated my two diagnoses.  I don't know what the connection would be, but an ophthalmologist once pointed out to me that the biggest sensory input to the brain is from they eyes, and we've said before that some consider the eyes to be an extension of the brain.

Bad news for Aduhelm just keeps coming -- and there's a price drop

Biogen and Aduhelm have certainly taken a lot of heat here in the United States, but they just took another hit over in Europe. 

The Committee for Medicinal Products for Human Use, or CHMP, recommended that the European Medicines Agency not approve Aduhelm to treat Alzheimer’s disease.  They acknowledged that it does remove beta amyloid plaques from the brain, but Biogen has not yet shown that the treatment actually improves cognition.  Biogen will be asking CHMP to reconsider its decision.  (We noted CHMP's intention previously, but this news makes it official.) 

In the US, the FDA approved the monoclonal antibody treatment, while acknowledging that Biogen still needed to show that it actually works.  And that will be a long process.  Biogen recently announced that they are beginning a new, international placebo controlled trial.  As we've seen before, ambiguous trial results lead to a protracted process of trying to understand the data.  I wonder if other, more effective treatments might move into center stage before Biogen can achieve this.

Not surprisingly, Biogen has been forced to drop the price of Aduhelm treatment from $56,000/year to $28,200 per year.

Have scientists finally discovered the cause of Alzheimer's disease? And can fasting help?

After all these years, have scientists finally discovered the cause of Alzheimer's disease?  This has been suggested by a number of news stories about some findings by researchers at UC Riverside.  They propose that we have focused too much on the beta amyloid plaques and not enough on tau protein.  The secret to Alzheimer's disease, then, lies in understanding the dysfunction of tau protein.  

If you read Beating the Dementia Monster you will recall that we discussed amyloid and tau as two possible pathways by which the disease might develop, but certainly not the only two.  You may recall our sub-chapter in the appendix, "Either? Both? Neither?"  Much of the recent focus on treating the disease has focused on the use of monoclonal antibodies (like aducanumab/Aduhelm) to remove amyloid from the brain.  But that hasn't led to the dramatic disease cure we had hoped for.

We further explained that tau protein is involved in the structure of microtubules in brain cells.  With the exception of red blood cells, microtubules are an important organelle in most cells in the body.  They act like a sort of skeleton in the cell, but also like a conveyor belt moving nutrients and other material around within the cell.  The tau proteins stabilize them.  (If you were in my 10th grade biology class, you would have been required to draw the microtubules in a cell.)  But if the tau proteins fail, the microtubules collapse into a "tangle."  So at autopsy, the pathologist will be looking for both amyloid plaques and tau tangles for evidence of Alzheimer's disease. 

An aside:  Physicist Sir Roger Penrose has suggested that microtubules, influenced by quantum mechanics, may hold the key to the "hard problem" of consciousness.  His thinking goes against the notion that the brain is just a very powerful computer, and human made computers might someday achieve consciousness.  Penrose shared the Nobel Prize in physics in 2020.

As a skeptic of the amyloid hypothesis, I was encouraged by one thing the UC Riverside researchers said, and that was that we have spent too much time looking at amyloid, and not enough study has gone into tau.  The research was led by Professor Ryan Julian.  Julian explained to reporters that most proteins remain in the body for a limited time.  If they remain too long, they may change in a way that causes them to become dysfunctional.  The body has systems for removing aging proteins, but these lose effectiveness with age.  Autophagy is the primary process for this.  And this process weakens in people over age 65.  So Julian's takeaway is that the progressive weakening of the process of autophagy may be the primary driver of Alzheimer's disease.

Enter intermittent fasting.  Intermittent fasting has been shown to be helpful with weight loss, metabolic syndrome, and other maladies.  Including Alzheimer's disease.  It works through a variety of mechanisms, such as inducing ketosis.  But it also induces autophagy.  At least if you do it aggressively enough.  From what I've been able to find out, a 20 hour/day fast is the minimum required to spark enough autophagy to help with Alzheimer's disease.  I don't know if the people saying that know what they're talking about, but I can't find anything to suggest differently.

I began intermittent fasting in January 2019, and I've held to a consistent 20 hour fast for nearly all of the time since then.  Especially in older people, an aggressive intermittent fast may have negative consequences, such as excessive weight loss.  My neurologist wonders if aggressive fasting has caused a recent escalation in the visual migraines that I have experienced since 2012.  My sister tells me that it impairs the uptake of calcium in the elderly, which is not good.  So don't do anything radical without talking with your doctor.  

But I also wonder if my fasting contributed to my improved test scores this year and the improved standing of my hippocampus volume in my recent MRI. 

Finally, some news.

It's been slow news, mostly due to covid, I suspect, so I have been fairly quiet.  But a couple of interesting items have surfaced recently.

One thing with me is that I've begun work on a Spanish edition of Beating the Dementia Monster.  It will be Vencer al Monstruo de Dementia -- or something like that.  I thought I could just run the manuscript through Google Translate and then scan it for major hiccups.  Well, machine learning has helped Google Translate to get pretty good, but it ain't perfect, and it trashed the footnotes in MS Word.  There are a lot of them, and they'll need to be reconstructed manually.  Some friends have connections with professional translators who may be willing to lend a hand with fine-tuning.  My Spanish is good enough that I should be able to find the big boo-boos, but I'll need people more skilled than I am for the fine-tuning.  We'll see where that all goes.

Another thing:  About two years ago I was invited to participate in a study of how Alzheimer's might affect speech, possibly leading to a diagnostic tool.  I submitted a short series of speech samples, but I didn't hear much after that.  As we discussed in Beating the Dementia Monster, I detected very definite changes in my speech as my disease began to develop, and I long believed there is an opportunity in the subject of speech to learn something about the disease.  There was an article in this week's ALZForum about progress in this field.

The article talks about a couple of studies, but not the one that I participated in.  I presume they followed similar strategies -- collecting and analyzing voice samples with artificial intelligence.  There are not a whole lot of conclusions yet, but it seems to be a topic of considerable interest.  The topic got a good deal of attention at the Clinical Trials for Alzheimer's Disease Conference in Boston, November 9-12.  A presentation by a British company called Novoic Ltd. claimed their AI-driven phone app can actually determine if someone is positive for beta amyloid.  That's after it has established the person has MCI.  (Test results for beta amyloid weren't that great so far.)  There are eight trials that are either completed (two), in-progress, or contemplated to test their app.  They seem pretty confident that it will eventually become an accepted diagnostic tool.

One thing that will be required to make any of these technologies work is one or more comprehensive databases containing voice and health history data.  The Alzheimer's Drug Discovery Foundation is trying to build such a database.