Conference First Day

 Today was the first day of our Washington State virtual conference for collaboration on making our communities dementia-friendly.  It runs two days, ending both days at noon.  I spoke this morning and will speak again tomorrow.  According to Zoom, we had a full 200 participating, but they anticipate another 30 or so will view the recording later.

Both days, my participation is as a discussion panelist.  There were four of us on today's panel, and there will be ten on tomorrow's.  Both days I lead off.

Both days, much of what we talk about is our reaction to earlier topical presentations.  Today, we reacted to the keynote speaker, an official with the organization Dementia Friendly America in Washington DC.  My main point was that I am very impressed with the toolkit the organization has developed to aid communities that have discovered they need to improve the habitability of their community for people with dementia.  I'm thinking that I'll likely follow up on that tomorrow, depending on whatever else I see before the panel discussion tomorrow.

Can flashing lights treat Alzheimer's disease?

A couple of weeks ago, my son sent me a podcast about research into using flashing light to reduce beta amyloid in the brains of laboratory mice.   The podcast was from the program Radiolab at WNYC radio in New York.  The research used the familiar model of mice whose genes had been edited to cause the brain to form beta amyloids, similar to what occurs in Alzheimer's disease.  

The researchers drilled a hole in the skulls of mice and inserted a fiber-optic thread down into the hippocampus.  In a way that's not clear to me, they had caused some cells to be light sensitive, and they pulsed light to these cells at a frequency of 40 Hz.  After just one hour, they found that forty to fifty percent of the beta amyloid had been removed!

In the new edition of Beating the Dementia Monster, we discuss the role of microglia cells in the brain in removing trash, including tau tangles and beta amyloid accumulation.  In older brains, the microglia can become less effective, and this allows the tangles and amyloid plaques to accumulate and complicate brain function.  This appears to play a role in the progression of Alzheimer's disease.

The ideas behind the pulsating light is that it re-invigorates one of the rhythms in the brain that, as in a computer, coordinates the activities of different components.  The rhythm in question is called gamma, and it seems to regulate the activity of microglia.  If age has caused the gamma to falter, this method promises to remedy that.  But drilling holes in your head?

The research is being led by Dr. Li-Huei Tsai at MIT's Picower Institute of Learning and Memory.  Dr. Tsai is a remarkable neuroscientist who has contributed substantially to many of the issues we have discussed on this blog.

So how does she propose to stimulate the gamma without invading the brain?  They put the mice into a room where they pulsed light at 40 Hz and got the same result -- a 50% reduction in beta amyloid.

But are the eyes and fiber-optic cables the only pathway from the outside world into the hippocampus?  What about the ears?  Dr. Tsai's team used a 40 Hz audio pulse, and got similar results ... with the mice.

An important question is, does this process result in improved cognition?  At least in mice, some of Dr. Tsai's tests suggest that it can even recover what might have been lost memories.

Will this work on humans?  In research, the record of applying the findings from mouse models to humans is pretty dismal.  Mice aren't people, and that's not really Alzheimer's disease in the mice.

Most of the work with mice was conducted in 2016, but clinical trials with humans began in 2019.  These are one year trials in which people with early stage Alzheimer's disease are subject to an hour a day of combined visual and auditory stimulation at the magic 40 Hz.  Test subjects are evaluated periodically, both for cognition and by MRI.  What are the results so far?  Dr. Tsai is pretty tight lipped, but she seems to be optimistic.

After the research was initially published, a few entrepreneurs developed devices to deliver 40 Hz light to consumers, and these are available at places like Amazon.  The research to support these is still ongoing, but, on the surface, the consumer items seem benign.  I would not advise using one, because they are unproven, and there are warnings that they may cause serious problems, especially for people with epilepsy.

Can contaminated surgical instruments spread Alzheimer's disease?

 Now there's a scary thought!  

A few years ago, some researchers found reasons to believe that amyloid seeds could be carried from one neurosurgery patient to another via surgical instruments.  This implies that contaminated instruments could transmit Alzheimer's disease between patients undergoing neurosurgery.  This in turn led to some alarming headlines.

Now, according to a recent white paper in the British medical journal The Lancet, this risk may exist, but it requires further study to be understood.  The white paper was the product of a working group gathered to investigate the risk.  It was analyzed in this week's Alzfourm.  

The working group concluded that there was little evidence that amyloid seeds could be transmitted during neurosurgery, but the risk shouldn't be dismissed.  Instead, it warranted a long-term epidemiological study.  It also recommended that surgical instruments used for neurosurgery in children be segregated from those used for adults.

If the seeds are actually transmitted, they would come from surgery involving older adults with evolving presence of beta amyloid in their brains.  Once transmitted to a younger person, the seeds would likely take 20 years to develop into a stage of Alzheimer's disease involving cognitive impairment.  Therefore, transmission from one older adult to another would be of much less consequence than transmission from an older adult to a young person. 

One person commenting on the article noted that there are a lot of serious risks that must be considered before any neurosurgery, and the benefits must outweigh those risks.  He suggested that, in comparison, the risk of developing "cerebral amyloid angiopathy" from contaminated instruments is minimal.  Cerebral amyloid angiopathy is a condition involving the familiar beta amyloid, and it is often, but not always, associated with Alzheimer's disease.  The commenter also suggested that further epidemiological study is warranted.  

Thank you so much!

Since my September 16 post on my participation in the Walk to End Alzheimer's, several of you have pledged to support me.  Thank you so very much!

Please Support Me

As you know, I have joined the board of directors of the Washington State/Northern Idaho chapter of the Alzheimer's Association.  This is the largest and most influential organization sponsoring research on Alzheimer's disease and providing support services to those afflicted and their families.  I rely on them for information on research and the effort to find an actual cure for my disease.  This effort is massive, and the need for funds is substantial.  Our biggest single fundraising drive is the annual Walk to End Alzheimer's.

Our local walk is on October 11, and I will, of course, be participating.  The event will be modified to accommodate covid-19 precautions, and I'm a bit worried this will reduce the excitement around the event.  Nevertheless, we are hopeful that we can meet our goals.

I'm writing to ask you to support me.  My personal page is here and you can make a pledge there if you are motivated.  I'm hoping that you will.

More Superfoods...

I first heard the term "superfood" during the HABIT study that we discussed in Beating the Dementia Monster.  It was the education module, and we were learning about diet.  The speaker referred to avocados as one of a set of superfoods.   I've been hearing about superfoods ever since.

I'll say again that I'm not comfortable with the concept of food as medicine.  My perspective is to just say, don't eat poison -- foods that cause inflammation and oxidation, or that make it hard to control your weight.

I've seen a number of lists of superfoods, mostly lists of 10.  All of them include blueberries, and none of them include avocados.  Nevertheless, I love avocados, and I eat one a day.  Recently, I encountered a column claiming to be the definitive list of superfoods.  Is it?  You can make up your own mind.

You can read the article here.  It was originally published in Outside Magazine in 2016.

This article lists 21 "superfoods" in ascending order, discounting the first 9 as not so great.  That was OK with me, because I like the foods in the second half a lot more than those in the not-so-great first half (actually the first nine).  But still no avocados anywhere.

The author of the article was wisely circumspect about the concept of the superfood. 

A surprise:  Coffee is a superfood.  Yay!  It comes in at #9 (from the top), so in the good half.  But green tea is even better at #7.

I'd never thought of kimchi as a superfood, but I was happy to see it listed in the first half.  Amy loves kimchi, but I don't.

Surprisingly, almonds were in the lesser nine.  The lesser nine were (in order of not-so-great to better):

• gluten-free flour
• orange juice
• coconut oil
• chia seed
• kimchi
• sweet potatos
• almonds
• beets
• acai
  

And so (according to the article), in improving order, the real supefoods are:

• eggs
• tart cherry juice
• broccoli
• coffee
• apples
• green tea
• black beans
• dark chocolate
• red wine
• salmon
• turmeric
• blueberries

I think blueberries have topped every list I've seen.  Although I may have seen one that had black beans on top.

Regarding turmeric, I have followed the advice of one of our blog readers to get turmeric in my diet.

The article has an interesting graphic that puts these on a two-dimensional chart that ranks them both on a scale of how super they are and on a spectrum of "delicious" to "disgusting."  On their chart, I'd have put beets closer to disgusting, and I'd have raised broccoli a lot closer to delicious.

 

Intermittent fasting, osteoarthritis, and cognitive improvement

During January and February I moved from an intermittent fast of 12 hours to 16 hours, to 18 hours, and then to 20 hours.  As we discussed in Beating the Dementia Monster, I had been doing a 12 hour fast since early 2016.  Now I have maintained the 20 hour daily fast since February 2020, with an eating window from 3 p.m. to 7 p.m.  So what has been the result so far?

First let me say that I would never have embarked on intermittent fasting, especially a 20 hour fast, were the incentive not there.  The incentive of preserving cognition in the face of advancing Alzheimer's disease is substantial and sufficient to keep me going.  Also, I would not have been successful if I were still eating a relatively high carbohydrate diet such as I lived before I found that I needed to lose weight.  Starting from the Mediterranean diet (or, in my case, the MIND diet) with relatively low carbohydrate consumption, fasting is much easier than it otherwise would have been.  After all, they degree of hunger you experience between meals is very much affected by high consumption of carbohydrates.  

So it's been seven months now.  As I reported earlier, after two weeks on the16 hour fast, the arthritis in my neck simply disappeared.  Against my doctor's counsel, I had been taking at least one ibuprofen every day.  I would tell myself that today I would stop, but by 9 in the morning the pain convinced my I should just take one more.  But suddenly I didn't need to take it anymore.  

I told you back then that, while the pain in my neck was gone, I continued to have pain in my lower back.  This was a nuisance, but it was not the continual pain that would prompt me to look for medication.  Well, it suddenly occurred to me a few weeks ago that I no longer have arthritis pain in my lower back.  The pain in my neck disappeared very suddenly, but the pain in my lower back faded more gradually.  Nevertheless, it's gone.

This was remarkable.  But my real goal was to improve my cognition, and this was promised in the research report in the New England Journal of Medicine that I discussed in January.  Obviously, this would be a much more protracted slog, because the improvement would need to come from the BDNF protein rebuilding lost brain cells.  Also, some doctors on the Internet speaking about Alzheimer's disease and fasting said that a 20 hour daily fast was necessary for the fast to be effective against Alzheimer's disease.   

So has there been any improvement in my cognition since I began the 20 hour fast?  And what measurements could I apply to even know?

In Beating the Dementia Monster, I told the story of how, after being diagnosed with Alzheimer's disease in 2015, my cognitive test scores rose steadily in 2016, 2017, and 2018.  Because I was being tested so intensively by both my care team and for some drug trials, they decided to give me a break in 2019.  So, while I did see my neurologist in 2019, I was not tested again until June 2020.

During this time I developed a set of tests to informally measure changes in my cognition.  One thing was to see how often I would forget to lock the car door when I went into the gym or a store.  I also had a set of about 50 3X5 cards with one or two syllable nouns written on them.  I would review the words on five cards, and see how many of the words I could remember later.  

And then I would see how fluidly I could speak in the Spanish language.  I began learning Spanish when I was 59, and for many years I have been speaking two or three times per week with friends in Latin America,  In so doing, I've found that my fluency fluctuates over time.  I'll do quite well for a period of time, but then my vocabulary and fluency will slip for a few weeks or months.

In fact, all of these measures, and a few others, appear to fluctuate together, so I do believe that I have a sense for what is going on with my cognition.

In June 2019 I told my neurologist that something happened in April 2019 that very suddenly affected my cognition.  It wasn't terrible, and I had no other symptoms, but something went wrong.  My sense was that my cognition stayed at a lower level, and may have continued to decline into the summer.  After reviewing my circumstances, my neurologist concluded that sleep problems were a factor, so I endeavored to improve the quality of my sleep.  

I believe that the success I had in improving my sleep helped with my cognition, but it did not go back to where it was at the beginning of 2019.  And then, in April 2020 (soon after I began intermittent fasting), my sense is that my cognition slipped again, although not to the extent it had in 2019.

That these two slips would both have occurred in April is not surprising to me.   Since moving from Hawaii to the Pacific Northwest in 1986, I have always had trouble sleeping in the spring, usually beginning in April.  Before we shift to Daylight Saving Time, the sun just comes up way too early, and the days are just too long.

When my cognition was tested in June 2020, the results were disappointing.  My neurologist and neuropsychologist conferred on this, and they reviewed my circumstances.  They concluded that my renewed issues were a consequence of stress, since I had been working on the new edition of Beating the Dementia Monster while taking on substantial new responsibilities.  I had no reason to disagree with them, so I finished the book and pared back on my commitments.  This felt really well, and I'm sure this has been helping.  I, of course, continue to fight for the best quality sleep I can get.  And I do think of it as fighting.

What prompted me to write this post is a strong sense that my cognition has actually improved since this summer.  I seem to be doing well on each of my little tests, and I have been speaking more fluidly (and fluently) in Spanish.  I have been quite pleased with my ability to recall and use words that I rarely use, and my use of various verb forms seems to be doing well.  

I would not say that I have returned to where I was at the beginning of 2019, but I am confident that, were I tested today, I would do much better than I did in June 2020.  I attribute this to sticking with the 20 hour fast in concert with each element of The Dementia Toolkit that I presented in the second edition of Beating the Dementia Monster.

Moving on from the mice...

Humans are the only animals that develop Alzheimer's disease.  The brains of dogs sometimes develop plaques and tangles that resemble those of Alzheimer's disease, but this does not lead to cognitive decline.  This makes them a poor candidate for studying the disease.

While rodents also do not develop Alzheimer's disease, mice can be genetically modified to produce a disorder that resembles Alzheimer's disease in humans.  So they have carried the load for the more invasive biological studies of neurodegenerative diseases.  But mice are biologically and behaviorally very different from humans, and research results based on a "mouse model" of human epidemiology is sometimes challenged.  So are there other animal models that more closely resemble human physiology and behavior?

At the recent AAIC 2020 conference, some Japanese researchers proposed the marmoset as a better animal model.  Weighing less than a pound, the marmoset is a small South American monkey whose brain much more closely resembles humans than does the mouse.  The researchers learned to edit the marmoset's presenilin 1 gene.  This is one of three genes responsible for young onset Alzheimer's disease in humans.  

The researchers propose that using gene-edited marmosets in future Alzheimer's research will produce more reliable results. This is because: 

• They have complex social behaviors and sleep patterns that resemble ours. 
• Their metabolism and immune systems are also more similar to those in people than those in rodents.  
• They can live 10 to 15 years in captivity, and typically develop tau tangles and amyloid plaques as they age. 
• The sequence of amino acids in their beta amyloid is identical to that of humans. 
• Raising and maintaining research colonies is feasible because these primates are small and produce many offspring.

One thing not discussed in any presentation I've seen is resistance from animal rights groups to invasive neurological tests.  I have seen resistance to the use of mice in Alzheimer's research, so I wonder how long it will take for resistance to the use of primates to develop.
  

Origins of the Superfood!

Because oxidative damage and inflammation play such an important role in the progression of Alzheimer's disease, we stress diets--like the MIND diet--that fight both factors.  In the battle with oxidation, perhaps it's blueberries that get the most attention, although there are many foods with antioxidant properties--as well as foods that help with inflammation.  Foods that fight both have come to be known as "superfoods."  But where did the concept of supefoods come from?

I read an interesting article that originated in Outside Magazine, "How Blueberries Became a Superfood."  The article traces the identification of blueberries as an unusually powerful source of health benefit to a researcher at Tufts University in 1996.  (The article tells the story through the eyes of the Maine wild blueberry industry.)  Then, in 2003, a book called The Color Code emphasized the colors of fruits and vegetables to identify their antioxidant properties.  And in 2006, another book brought together the antioxidants, anti-inflammatories, and other health promoting foods, and the concept of the superfood was born.  The latter book was appropriately entitled SuperFoods Rx; Fourteen foods that will change your life. 

I have to admit that I struggle with the concept of food as medicine.  Rather than eating foods to prevent disease or heal you, my paradigm is just don't eat poison.  Or as some put it, eat real food.  Refined sugar and flour, corn sweetener, and many food additives are poison.

While antioxidants are said to have many health benefits, including some with respect to cancer, the article focused on the benefit to the brain.  They discussed research on the effect of antioxidants on brain health, including some that found mice fed lots of blueberries performed better on tests of memory.  In fact, they found mouse brains stained by blueberry pigment, suggesting that the antioxidant pigment molecules could cross the blood-brain barrier.  (We discuss the blood-brain barrier in the second edition of Beating the Dementia Monster.)

The author of the article points out that many researchers emphasize the need for variety in your diet.  Don't just eat the same anti-oxidants and anti-inflammatory foods every day, because the whole is probably greater than the sum of the parts.  In other words, each of the healthful foods has its own benefit, and you need to rotate what you eat to be getting the full benefit of what's out there.