More on air pollution and Alzheimer's disease

We've written before about research on a link between air pollution and Alzheimer's disease.  We know, for example, that people living near freeways are more likely to develop Alzheimer's disease.  An hypothesis about this has been that oxides of nitrogen enter the blood stream through the lungs and then find their way to the brain.  Meanwhile, fine particulates follow the path of the olfactory nerve from the nose to the brain.  And, apparently, changes in levels of air pollution can be correlated with changes in the incidence of dementia.  So there appears to be a cause and effect relationship.

Recent research at the University of Washington's Alzheimer's Disease Research Center has gone further in confirming the relationship.  The Winter/Spring issue of Dimensions; the magazine of the UW Alzheimer's Disease Research Center carried an interesting article on the research.  The research was published in the journal Environmental Health Perspectives in August 2021 as "Fine Particulate Matter and Dementia Incidence in the Adult Changes in Thought Study."  It drew on data from the ongoing and extensive study, "Adult Changes in Thought,"  (ACT) which began in Seattle in 1994.  Over the years, ACT has produced a huge trove of data that is being used by Alzheimer's researchers all over the world.  

In this case, researchers used measurements of levels of airborne pollutants in various neighborhoods around Seattle going back to the 1970s.  The study examined over 4,000 Seattle ACT participants, specifically focusing on about 1,000 who developed dementia during the course of the study.  They correlated the addresses of the participants with the levels of fine particulates measured in their neighborhoods.  While the instruments used to measure the particulates varied over the decades, the researchers used a new air pollution exposure model to estimate exposures from 1978 to 2018.  The study concluded "the evidence suggests that air pollution has neurodegenerative effects, and that reducing people's exposure to air pollution could help reduce the burden of dementia."

A finding was that a difference in air particulate levels of 1 microgram per cubic per cubic meter (that's not much) between neighborhoods could be associated with a 16% difference in incidence of dementia.  They article noted that this is about the difference in levels measured at Pike Street Market (origin of Starbuck's Pike Place coffee and near downtown) and those measured in residential areas around Discovery Park.  Discovery Park is near where one of our sons and his family live and is well away from the pollution-generating activities down town.

How much are covid-19 and Alzheimer's disease alike?

As of this week, about 5.9 million people have died from covid-19 world-wide with more than 400 million confirmed cases.  The most common immediate causes of death are related to the respiratory system via covid pneumonia and damage to the heart.  But this is a complex infection, and it affects many organs of the body -- including the brain.  According to this recent study published in the journal Alzheimer's and Dementia, its attack on the brain is sometimes very similar to that of Alzheimer's disease.

You have almost certainly heard that loss of smell is a symptom of covid.  Well, according to the study, loss of smell is also sometimes seen in early stages of Alzheimer's disease and is evidence of neurological damage.  Headaches are also a symptom.  And what is a headache other than evidence of inflammation in the brain?  As we explained in Beating the Dementia Monster, inflammation in the brain is a key part of the process by which Alzheimer's disease evolves.  And you have likely heard that people with covid report "brain fog."

The researchers who performed the study reviewed the available literature on the disease.  In their own laboratory, they also examined brain tissue from people who had died from covid as well as brain tissue from a control population.  The upshot is that they found evidence of both oxidative stress and inflammation in covid patients similar to that of Alzheimer's disease patients.  While they don't say that they found the tau tangles which are markers of Alzheimer's disease, they did find the mechanisms that lead to tau tangles appeared to be in motion.  (They did not, however, find beta amyloid plaques or evidence that beta amyloid was even forming.) 

So what do we make of this?  It seems likely that people with Alzheimer's disease are at risk of having their condition aggravated by covid, perhaps significantly.  And since Alzheimer's disease likely begins 15 years before the first symptoms, there are a lot of undiagnosed people out there who are getting covid.

The authors believed that the primary contribution is to have found a link between the brain's inflammatory response to covid and the way the tau protein degenerates in Alzheimer's disease.  They are hoping this will lead to treatments for damage to the brain caused by covid.

Aduhelm -- still in the news

A few weeks ago we wrote that the Centers for Medicare and Medicaid had proposed a system in which they would only cover Aduhelm for patients enrolled in a clinical trial.  This would exclude people without access to a trial, and trial enrollment could be limited.  The proposed decision requires a 30 day public comment period ... and boy, are there comments.  A record number of comments.  Not surprisingly, there are comments for the draft and comments against it.

So who's for and who's against?  In this politicized age, people wonder about red states and blue states.  Apparently, red states tend to oppose the proposed decision, as 78 Republican congressmen have signed a letter demanding greater access to the treatment.  But 4,600 comments favoring the decision came from a political organization aligned with Bernie Sanders.  

It's been noted that the comments result from organized campaigns, since the language in many letters are very similar to the language in others.

The comment period ended February 10, and a decision is expected in April.  If you're curious, you can read more here.

A touching story and some insights

I came across an article in WebMD about the father of a freelance journalist, Lisa Marshall.  Her father had Alzheimer's disease, and she tells the story of his decline interwoven with insights on how to avoid or cope with the disease.  She also highlights two specific areas of new hope.

Consistent with what we say in Beating the Dementia Monster, she has a lot to say about her father's lifestyle and how his eating, exercise, smoking, sleep, and other habits likely contributed to his development of Alzheimer's disease.  These have become lessons learned in her family.  

She also discusses Aduhelm, acknowledging its, so far, poor showing in clinical trials.  But she also reports on the hope Aduhelm provides a possible step on the path to finding more effective drug treatments.  And she discusses the significance of new blood tests which may show us that the disease mechanisms are in motion long before symptoms appear.

She writes about transcranial magnetic stimulation as a treatment.  We wrote about this in January 2020.  This has been approved by the FDA for treatment of depression, but it may also be effective against Alzheimer's disease.

While she had little to say that we haven't already covered in Beating the Dementia Monster and in this blog, what fascinated me was the story of her father.  He was an accomplished physician with many deeply intellectual interests.  Marshall uses these to underscore the terrible loss her family experienced in his decline over about 15 years.

The story is a reminder of the terrible cost of Alzheimer's disease, but also of the love within families that may be tested but is also a source of strength in confronting the disease.  Of course, it also outlines what we can be doing to forestall its appearance or its advance.

My Spanish language YouTube presentation

At the behest of a friend who wants to spread my influence in Latin America, I made a YouTube video in Spanish similar to what I present when public speaking.  It has occupied much of my time for a couple of weeks.  If you're curious, you can see it here.  

I start out with pronunciation that's about as well as I can do, but it deteriorates later in the video.  I'd like to do it over some day with better pronunciation throughout, but it's so time consuming.  (Preoccupation with it has impeded me somewhat from posting to this blog.)

I continue working on a version of Beating the Dementia Monster in Spanish, but that's a lot of work too.

All stop on atuzaginstat?

Back in January 2021 we wrote a couple of times about the proposed drug therapy atuzaginstat ... or COR388.  We also discussed it in the appendix of the second edition of Beating the Dementia Monster.  We thought it was a promising approach to treating Alzheimer's disease by going after the bacteria p. gingivalis.  We explained that there is correlation between gum disease caused by p. gingivalis and Alzheimer's disease.  We were hopeful that treating the bacteria would treat AD.  But the FDA just ordered full stop on the phase 2/3 trial.  The sponsoring company, Cortexyme, reported halting the research in this press release.  And then their stock price fell 34%.

Why the stop?  The FDA ordered it after a review of the trial data identified hepatic adverse events.  So it's about safety.  It's not clear to me if the data also showed or failed to show any improved memory or cognition.

But all is not lost.  Cortexyme has another drug, COR588, that is already in clinical trials in Australia.  It is a more advanced drug that pursues the same hypothesis as COR388 -- attacking p. gingivalis will improve memory and cognition.  It seems to be safer and more effective.

You should already know that I am somewhat skeptical of the amyloid hypothesis and its implications -- that removing beta amyloid from the brain is the right way to treat Alzheimer's disease.  This is the guiding principle behind most of the pharmaceutical therapies under development.  I'm hopeful that going after p. gingivalis instead will be more rewarding.

No cheese -- Why not??

When I speak to a group about lifestyle changes to prevent or slow the advance of Alzheimer's disease, I hear the loudest groan when I talk about diet ... notably when I say that the MIND diet rules out cheese.  That's because everyone loves cheese.

Cheese and other saturated fats were implicated in heart disease for many years, but they were somewhat rehabilitated during the 1990s.  This rehabilitation is controversial, and the fact that most saturated fats have animal origins prompts those wishing to protect animals to influence the debate.  It's been my observation that, over the past two years or so, the consensus of online authoritative sources has shifted from a relatively benign view of saturated fat to a more critical one.  And so some authorities discourage the consumption of saturated fats (for example here and here), while others cite less critical research to permit moderate consumption (for example here and here).  We discussed this in Beating the Dementia Monster, citing the writing of Dr. Mark Hyman, and his book Food; What the heck should I eat.

Regardless of how one might come down on the debate with respect to heart disease, research by the late Dr. Martha Clare Morris sustained the strike against saturated fat with respect to Alzheimer's disease.  (See her book Diet for the Mind.)  Neurologists like to say "what's good for the heart is good for the brain," and there is a strong correlation between heart disease and Alzheimer's disease.  So shouldn't the influence of saturated fat on heart disease (whether strong or weak) have a consistent influence on Alzheimer's disease?  

Well, apparently not.  Dr. Morris's research seems to dissociate the two effects.  (Again, this is all controversial with respect to heart disease, and everyone cites their favorite research.)  

When I was preparing the second edition of Beating the Dementia Monster, I puzzled over this apparent anomaly.  Of course, my underlying assumption was that a negative effect on saturated fat should come to the brain via a negative effect on the cardiovascular system.  But maybe that's not true.  And I've found something to suggest an explanation.

Several times on this blog we have discussed the gut-brain axis.  There is a poorly understood relationship between what goes on in the gut and what goes on in the brain.  Most of it hinges on the activity of many different bacteria (and archaea) in the gut.  So when the life of the "microbiome" in your gut is disrupted by antibiotics or the wrong kind of nutrients, it can adversely influence the brain.  And on this blog, we are very interested in influences on the brain that promote or discouraged the advance of Alzheimer's disease.

I got to thinking about this today when I was at the gym watching this video about diet and the gut microbiome.  This particular channel is big on promoting a vegan or vegetarian lifestyle (and so may be a bit biased), but I found what they were saying compelling.  (Acknowledging that they may be biased is not to discount their authority, only to acknowledge that every source is biased in some way, and we are wise to always consider that in assessing what someone is telling us.)  

What caught my attention was a statement that cheese has a bad effect on the gut microbiome.  If so, that would explain it.  Cheese (and other saturated fats) may be getting something of a pass with respect to cardiovascular disease, but it's still a recognized and important factor in the development and advance of Alzheimer's disease. 

So cheese is bad for brain health, but not because it affects the cardiovascular system.  It affects the gut microbiome.

So what do the recommend that you eat?  After discussing the affect of different nutrients on the gut, the presenter reviewed the best foods to eat for gut health.  Well, guess what ... everything she named as being positive for gut health is right out of the MIND diet.  

Of course, we discuss the MIND diet in Beating the Dementia Monster, and I've been trying to follow it now for several years.  I'm sure it's making a contribution to my success in dealing with Alzheimer's disease.