Beating the Dementia Monster on TV in New York ... sort of

This morning I got an email from the director of marketing and communications for the Washington State chapter of the Alzheimer's Association.  She told me about this TV news story from New York about a man aggressively fighting MCI.  He said he had read books about MCI, and the camera showed several of them on his table.  They didn't talk about it, but one of the books was Beating the Dementia Monster.

They discussed what the man is doing to fight his MCI, and they showed him getting aerobic exercise on his morning jog.  They ran through most of the tools in the dementia toolkit, indicating that these were what he was doing.  (They didn't mention "The Dementia Toolkit" by name, they just listed what he has been doing.)

It would be nice to have the book be mentioned by name somewhere to get some more exposure.  We're still selling four of five books a day, and we've sold more than 7,500 copies when both editions are counted together.  But we're not selling the 20 books a day we were before Amazon clamped down on our advertising.

(Amazon's clampdown was a blanket prohibition on advertising on Amazon of any book that claims to show how to slow, treat, or cure any disease.  It doesn't matter which disease or how well founded or documented the claims are.  It's a long-standing rule that they seem to have started enforcing when covid-19 was new.  I guess they're worried about circulating covid misinformation.  I see a lot of books by highly regarded medical experts are no longer advertised on Amazon, so I don't think they're picking on me.)

Personality type predicts dementia?

Back in the 1980s and 90s, I, along with many others, was fascinated with the Myers-Briggs Type Indicator.  You could take a test and find out which of 16 boxes your personality might fit into.  It was kind of fun, and you could play parlour games with it.  However, I began to believe that it was dangerous in that it encouraged people (like me) to unfairly pass judgement on others.  It could also mean the difference between getting or losing out on a job when the HR department used it to screen people for different roles.  I'm not sure it did such a great job at that.  In time, the Myers-Briggs system was replaced by the "Big Five" personality traits, but I'm not sure it garnered the same level of attention in popular culture as the earlier system.  But to psychologists, the Big Five system was a superior way of assessing someone's personality and aptitudes.

A question that occurred to me a long time ago was whether personality type might predict whether someone might develop Alzheimer's disease ... or any type of dementia.  I guess I wasn't the only one with this question, because researchers have found some interesting correlations.  One such study was published in the September 2021 issue of the journal Biological Psychiatry.

The study found correlations with two of the Big Five traits.  But first, what are the traits?  You can read up on them in this Wikipedia article, but here they are:

1. openness to experience (inventive/curious vs. consistent/cautious) 

2. conscientiousness (efficient/organized vs. extravagant/careless) 

3. extroversion (outgoing/energetic vs. solitary/reserved) 

4. agreeableness (friendly/compassionate vs. critical/rational) 

5. neuroticism (sensitive/nervous vs. resilient/confident)

So what did the study do?

The researchers gave participants from the Baltimore Longitudinal Study of Aging the Revised NEO Personality Inventory to identify where each stood with respect to the Big Five traits, and they administered PET scans to determine their load of amyloid and tau in their brains. The presence of beta amyloid peptides and certain tau proteins signal the advent of Alzheimer’s disease. 

And what did they find?

"Higher neuroticism and lower conscientiousness are risk factors for Alzheimer’s disease and related dementias, but the underlying neuropathological correlates remain unclear."

The underlying neuropathological correlates remain unclear, but allow me to speculate.  I wonder if people with lower neuroticism and higher conscientiousness aren't just people who are more likely to adopt a healthy lifestyle, a lifestyle that touches on each element of the Dementia Toolkit we described in Beating the Dementia Monster.  They may be people more likely to get exercise, eat right, adopt good sleep habits, maintain social connections, and remain interested in learning.

Others are thinking the same thing.  Commenting on the research, Dr. Claire Sexton of the Alzheimer's Association told Medical News Today,“One potential pathway is inflammation, which is associated with personality and the development of Alzheimer’s biomarkers.  Lifestyle is another potential pathway.  For example, highly conscientious individuals have been shown to have healthier lifestyles — in terms of physical activity, smoking, sleep, depression, cognitive stimulation, etc. — than those with lower conscientiousness.  There is a solid body of research connecting lifestyle, dementia risk, and biomarkers.” 

Dr. Antonio Terracciano, a professor in the Department of Geriatrics at Florida State University, also suggested, “There are aspects of neuroticism and conscientiousness that might directly impact the risk of dementia. Traits like neuroticism shape our emotional life, the way we cope with stress and deal with our feelings. Conscientiousness is defined by our level of grit, persistence, and planful attitudes.” 

So there is correlation, but causation is a bit more murky.

Hearing loss, cataracts, and dementia

Back in December, we wrote about research finding that people who had cataract surgery had a 30% lower probability of developing dementia.  I speculated that there might be a relationship between that and a higher incidence of dementia among people with hearing loss.  Recently, other researchers are seeing a similar connection.  In August 2020, we wrote about a Lancet commission report identifying both hearing loss and loss of vision as modifiable risk factors for dementia.  Combined hearing and vision problems may increase the risk of dementia by 50%.  The hope is that aggressively addressing both of these would significantly lower the incidence of dementia.  

Why should such a correlation exist?  One idea is that sensory dysfunction interferes with social connection which is important to resisting dementia.  If you can't hear people or can't see them well you are likely to simply withdraw socially.  And that's deadly.  

But recent research suggests a broader problem.  Failing to control for sensory dysfunction may be skewing statistics about the prevalence of the dementias.  We wrote earlier this week about the Alzheimer's Association Facts and Figures Report.  The report devoted space to how difficult it has been to accurately count people afflicted by different dementias.  

This week's ALZForum had this article on the correlation between sensory dysfunction and dementia.  One thing they noted is that people who don't see or hear well don't do well on cognitive tests, especially tests involving language and memory.  So the apparent correlation may be partly due to over-counting people with dementia simply because they don't test well.

Good stuff in the 2022 Alzheimer's Association Facts and Figures Report

Readers of this blog know that in March of each year I eagerly anticipate publication of the Alzheimer's Association Facts and Figures Report.  The 2022 edition is now out, and I have just finished reading it.  (See it here.)  I thought this year's edition was especially useful, and I'd like to share with you my takeaways.

Each year has a special theme.  Past themes have featured topics like the burden of dementia on caregivers and the cost of care for Alzheimer's patients.  This year it's about mild cognitive impairment (MCI).  If you read Beating the Dementia Monster, you know that MCI is my diagnosis with the statement that my MCI is most likely due to Alzheimer's disease.  We recall that Alzheimer's disease is finally diagnosed in the autopsy, but medical science has been sharpening its tools for diagnosing those of us who are still living.  So this issue was particularly interesting to me.

You will recall that MCI is one stage of the disease on the way to dementia.  MCI ends and dementia begins when the patient is no longer able to conduct all daily tasks without assistance.  In Beating the Dementia Monster, we describe the stages of Alzheimer's disease as 1) preclinical (or prodromal), 2) "MCI due to Alzheimer's disease," and 3) "Alzheimer's dementia."

I found interesting facts throughout the report, not just about MCI.  So here are some of them:

1.  The accuracy of the statistics we have on the prevalence of Alzheimer's disease, Alzheimer''s dementia, and MCI due to Alzheimer's disease has been improving.  The challenge of counting those in the various stages of Alzheimer's disease are confounded by the reluctance or inability of many doctors to diagnose Alzheimer's disease and the other causes of dementia and death that so often appear alongside Alzheimer's disease.  New studies are trying to improve how the statistics are gathered.  But here are the latest numbers of interest to me.

-- We believe that 6.5 million Americans are now living with Alzheimer's disease.
-- Ten percent of people 65 years of age or older have Alzheimer's dementia.
-- Broken down by ages, the following have Alzheimer’s dementia: 5% of people age 65 to 74, 13.1% of people age 75 to 84, and 33.2% of people age 85 and older. 

-- At the moment, our best estimate is that eight percent of Americans 65 and older have MCI due to Alzheimer's.  But that appears to be much lower than the likely true number.

 

BUT -- 15% to 30% of those diagnosed with Alzheimer's disease while alive are found not to have the brain changes associated with the disease on autopsy.  So there are a lot of false positives, and these are only recognized when there is an autopsy.  This, of course, is another factor skewing the statistics. 

 

2.  Only 0.1% of the population is believed to have younger-onset Alzheimer's dementia.  Younger onset dementia strikes when someone is in their 50s or even younger.

 

3.  MCI due to Alzheimer's disease is hard to diagnose.  It requires biomarker evidence like MRIs and PET scans.  When diagnosed at the level of the primary care provider (PCP) these may not be ordered, and the accuracy of our statistics needs to be improved. 

4.  Clinicians often don't tell their patients about a diagnosis of Alzheimer's dementia.  (I don't know if they still tell their families.)

5.  The higher prevalence of Alzheimer's disease in women may be explained by the fact that, in the World War II generation, far fewer women went on to higher education.  As we explained in Beating the Dementia Monster, learning, especially when you are younger, has a protective effect with respect to Alzheimer's disease.  Less higher education would mean higher incidence of the disease later in life.

6.  In the same way, the doors to higher education for African Americans and some other minorities who are now 65 and older were not as wide open as they were to people of European ancestry.  Not surprisingly, we find a higher incidence of Alzheimer's disease among them.  This should inform our approach to studying Alzheimer's disease in these populations.

7.  The best quality statistics available are actually for Americans of Japanese ancestry, and they show the lowest incidence of Alzheimer's disease of any ethnic group.  (My wife is of Okinawan ancestry, and Okinawans live the longest of any population on the planet.  I'm not sure about the influence of an American diet on those who were born here and grew up here ... with American fast food, exercise habits, etc.)

8.  Black and Hispanic populations have higher incidences of diabetes and cardiovascular disease, and those are associated with higher risk for Alzheimer's disease.  When studies control these factors, incidence of Alzheimer's disease in these populations appears to be consistent with those of European ancestry.

9.  Alzheimer's disease was the sixth leading cause of death in the United States in 2019, but the seventh in 2020 and 2021.  Why did it go down?  Because covid debuted at number 3 in the list in 2020 and moved Alzheimer's disease down a notch.

 

10.  Covid 19 very much confused the process of keeping statistics on deaths from Alzheimer's disease.  It was difficult to make a distinction between people dying from Alzheimer's or dying with Alzheimer's.  If someone dies who had covid 19 and Alzheimer's disease, what should the death certificate say about cause of death?  How should that death be applied in the statistics tracking both diseases?  And what of people with Alzheimer's disease aggravated by the lockdowns and subsequent social isolation?  (We wrote about this back in May 2020 regarding the death of a friend of mine.)

 

11.  The report featured a striking chart depicting the changes in the numbers of deaths due to various causes between 2000 and 2019.  While deaths (as a percentage of all deaths) due to heart disease, stroke, and HIV were down, deaths due to Alzheimer's disease were up a whopping 145%.  Of course, when deaths due to some causes go down, deaths due to other causes will go up.  When people live longer, they are more likely to die of Alzheimer's disease.  And the treatments for other diseases are far more advanced than treatments for Alzheimer's disease.  

12.  Two thirds of people who die of dementia live in nursing homes.  That compares to 20% of people who die in nursing homes of cancer and 28% of people who die of all conditions.

13.  They again devoted considerable space to the burden of care-giving.

 

14.  Caregivers with spouses who died with dementia were much more likely to die within a year of the death of the patient than when the patient died of other causes.  This reminded me of the deaths of two women that we knew well who died less than a year after their husbands died with dementia.

 

 15.  Fifty-five per cent of PCPs report there are not enough dementia care specialists in their communities.  Also, more training is needed for PCPs and non-physician dementia care workers.

16.  The report focused on why we should be paying attention to people with MCI even though they are still able to care for themselves.  

17.  Twelve to 18 per cent of Americans over 60 are living with MCI.  Ten to 15 per cent of these will transition from MCI to dementia each year.  (Quick fake math:  If I developed MCI in 2014, each subsequent year I should have had about a 12% chance of the MCI evolving into dementia.  Consistent with what a neuropsychologist told me in 2017, I should be dead by the time I'm 75 -- three years from now.  I tell about the discussion with the neurologist in Beating the Dementia Monster.)

 

18.  One third of people diagnosed with MCI develop Alzheimer's dementia within five years.  (This statistic is not new.  We examined it in Beating the Dementia Monster.)  But some do not.  It's not clear to me -- and is likely unknown -- how many with MCI due to Alzheimer's do not develop dementia.  Usually when someone has MCI we just don't know if it's due to Alzheimer's disease.  My bet is that in cases of MCI due to Alzheimer's (as opposed to other causes of MCI) all develop Alzheimer's dementia at some point.

19.  It is a challenge to distinguish between individuals with memory loss due to normal aging, due to all causes of MCI, and MCI due to Alzheimer's disease.  This confuses our statistics.

20.  There is a distinction between amnestic MCI and nonamnestic MCI.  In amnestic MCI memory issues predominate, while in nonamnestic MCI other issues like visuospatial perceptions, language, and executive function predominate.  In Beating the Dementia Monster, we discussed "the four syndromes."  One of the syndromes was amnestic MCI, but we further broke nonamnestic MCI down into three more syndromes.  My first symptoms appear to have been nonamnestic, for example problems seeing pedestrians in the crosswalk.  (So I stopped driving.)

21.  This article from the journal Neurology was frequently cited throughout the portion of the report dedicated to MCI.  You don't need to read it.  There's nothing in it that you didn't learn when you read Beating the Dementia Monster -- except that, in medicine, there is growing reliance on the lifestyle changes we characterized in "the dementia toolkit" as the primary approach to confronting MCI.

22.  Nearly half of people diagnosed with MCI were found to be cognitively normal after 2.4 years.  I'd bet that most of these MCI cases were caused by medications that were later changed.  It's fairly common for a medication to cause MCI, and the MCI clears up when the medication is changed.

23.  There was discussion about increased use of PET scans to diagnose Alzheimer's disease more confidently.  As we discussed in Beating the Dementia Monster, PET scans are expensive, and you need good justification to get the insurance company to pay for one.  This has changed now that Aduhelm is approved for treatment of Alzheimer's disease.  You don't want to spend all that money for Aduhelm and risk brain hemorrhages when your MCI was really caused by your meds.  So insurance companies are now more willing to pay for a PET scan.  I would definitely like a PET scan to confirm the conclusions my neurologists made from my many MRIs.

24.  Because Alzheimer's disease is most effectively addressed in earlier stages, there is a push to not only use PET scans in diagnosis, but also to move forward with approval of blood tests to diagnose Alzheimer's disease.

 

25.  There are currently 104 treatments for Alzheimer's in clinical trials or in some other stage of the regulatory approval process.

26.  About 80% of Americans diagnosed with MCI do not want to see a doctor after experiencing symptoms of MCI.  I think this is tragic, and it largely comes from the well-circulated idea that there's nothing that can be done for Alzheimer's disease.  I've met too many people that just give up when they think they may have a serious memory issue.  As we explain in Beating the Dementia Monster, there's a lot that can be done to fight the advance of cognitive decline.

27.  But then a third of PCPs are not comfortable diagnosing MCI due to Alzheimer's disease.  They cite difficulty in differentiating MCI from normal aging (72%) and difficulty in interpreting patient reports of daily functioning (51%).

28.  Fewer than one in five Americans have heard of MCI.  This doesn't surprise me.  The first time I heard of MCI was when I went to a neurologist over my memory and cognition issues.  (I've learned a lot since then.)

29.  85% of Americans say they want to know if they have MCI, but only 40% say they would talk to their doctors right away if they experienced symptoms.

30.  Only 40% of PCPs say they are familiar with biomarker tests for Alzheimer's disease.  As a consequence, when MCI is detected, only 18% of patients are referred for further testing.  

This is my condensation, but there was a lot more.  If you're interested in this sort of thing, it would be well to download a copy and read it yourself.

Sleep -- How can the circadian rhythm in sleep affect Alzheimer's disease?

In Beating the Dementia Monster, we discussed very recent findings on the role that sleep, especially deep sleep, plays in Alzheimer's disease.  It's in deep sleep that the shrinkage of neurons and the slowed rhythm of brain waves promotes the clearing of trash from the brain.  That trash includes both the beta amyloid peptides and tau protein tangles that are part of the progress of the disease.  We said that good sleep is really important to resisting both the initiation and progress of Alzheimer's disease.

But who gets a good night's sleep any more?  As Dr. Matthew Walker wrote in his best-selling book Why We Sleep, as we get older, our brains atrophy, and the part of the brain that controls sleep becomes less effective.  In Alzheimer's disease, the atrophy accelerates, and our ability to sleep well is increasingly impaired.

Another factor in sleep is our circadian rhythm that governs many functions of our bodies throughout the 24-hour day.  This includes when our bodies are interested in sleep and when they will insist on waking up.  Walker cites the "Early Bird Specials" at restaurants that appeal to older people.  He says that, as we age, our circadian rhythms advance, so that we want to go to bed earlier -- and get up earlier.  (And so older restaurant customers want to eat earlier.)  If we don't go to bed earlier, we'll still awaken earlier and get less sleep.  I used to go to bed at 11, but I deliberately changed my bed time to 9:15, although I have a hard time getting my head on the pillow before 9:30.  To fight insomnia, I try to stay as consistent with my bed time as I possibly can.

But is there one circadian rhythm for the whole body, or do many parts have their own control systems?

My friend Teale recently sent me an article from The Conversation about research on rhythms that can be traced to the cells, especially certain white blood cells called macrophages.  As we learned in high school biology, white blood cells play a role in the immune system.  Like amoebas (and The Blob), they engulf and absorb their prey.  Back in July 2020 we wrote about "cytokine storms" and their complex relationship to both the beneficial and destructive roles of inflammation in the brain.  The cytokines arise from the macrophages.

The article was based on this research which you may -- or may not -- want to read.  I leave it to you to decide.  It's called "Circadian control of heparan sulfate levels times phagocytosis of amyloid beta aggregates."

The researchers gave macrophages from mouse brains the opportunity to eat up amyloid beta molecules.  They found that they devoured the molecules differently at different times of the day, and the timing was controlled by molecules in the cells that apparently respond to the body's circadian rhythm.  This seems to be synchronized with the periods of sleep most noted for controlling Alzheimer's disease.

We have, of course, our standard disclaimer on mice:  Mice are not people.  Many discoveries made with mice turn out later to be unrelated to how the human brain behaves.  

Nevertheless, we know for sure that getting good sleep fights Alzheimer's disease.

Once Alzheimer's disease starts, how long until the first symptoms appear?

As we explained in Beating the Dementia Monster, Alzheimer's disease may begin as much as 15 years before the first symptoms appear and 20 years before actual dementia.  Now new tests are emerging that can determine that someone has developed Alzheimer's disease before there are symptoms.  So if you find someone has presymptomatic (or "prodromal") Alzheimer's disease, is it possible to predict when actual symptoms of memory loss etc. will begin to appear?  Well, apparently so, and with a good bit of accuracy.  Well, maybe not from the very beginning of the disease, but at least from when the amyloid plaques begin to form. 

We know that in Alzheimer's disease, variant forms of amyloid peptide (strings of amino acids that were supposed to be proteins but got sidetracked) and variants of tau protein appear in the brain.  There is more than one variant of each with varying levels of toxicity.  The problematic version of amyloid forms the plaques and the tau forms the tangles we discussed in Beating the Dementia Monster.  The plaques and tangles continue forming until the brain reaches a "tipping point" when there's an explosion of tau tangles throughout the brain.  

So researchers would like to measure the time from when the first plaques appear to when the first symptoms appear.  And it appears that's a fairly well defined and regular time period.  Researchers at Washington University Saint Louis measured the amount of the protein known as p-tau217 in cerebrospinal fluid and found that it rises at a pretty consistent rate among different people after passing the tipping point.  This means that if you know someone's age when they reached the tipping point, you can predict when symptoms will begin with reasonable accuracy.  The research results were presented by Dr. Suzanne Schindler at the TAU2022 virtual Global Conference this past February 22-23.

So why would we want to know this?  Primarily as an aid in clinical trials for different treatments, especially those (like aducanumab) directed at dealing with amyloid plaques.  The expectation is that a new, effective treatment for Alzheimer's disease must be active during the preclinical phase of the disease -- before the first symptoms.  Researchers measuring the effectiveness of a given treatment will want to know throughout the trial how far the disease has progressed and anticipate when symptoms will begin to present. 

So why do I care about this?  Mostly I just thought it was really interesting to learn how consistently the disease develops among different people.  However, since the symptoms manifest with varying effect in different people, I'm led to speculate that, while the underlying disease may advance similarly in different people, life style choices nevertheless influence the severity of the symptoms.  In Beating the Dementia Monster, we discussed the Nun Study.  In the Nun Study, Sister Mary lived to be over 100 years old and appeared to be cognitively healthy.  But her autopsy found that her brain had been ravaged by Alzheimer's disease.  This has been correlated with her healthy lifestyle. 

Hyperbaric Oxygen Treatment

My college classmate, Roy, sent me this article on "hyperbaric oxygen therapy" (HBOT) for Alzheimer's disease.  I could have sworn that I had written about this before, but I can't find it in the blog archives.  I do recall having investigated it and found that the treatment is offered here in my own small city, and some claim their treatment will treat Alzheimer's disease.  But I also recall being a bit squeamish about the caliber of the clinics offering it.  I'm thinking I was going to ask my neurologist about it and then totally forgot about the whole thing.  Or maybe I did, and she didn't like the idea.  But I don't remember at all.  (I'll have another opportunity to bring it up with her in early May.)

HBOT is, however a recognized treatment for a number of ailments, including:

• Severe anemia
• Brain abscess
• Bubbles of air in your blood vessels (arterial gas embolism)
• Burns
• Carbon monoxide poisoning
• Crushing injury
• Deafness, sudden
• Decompression sickness
• Gangrene
• Infection of skin or bone that causes tissue death
• Nonhealing wounds, such as a diabetic foot ulcer
• Radiation injury
• Skin graft or skin flap at risk of tissue death
• Traumatic brain injury
• Vision loss, sudden and painless

 So far, it's just not formally approved for Alzheimer's disease.

What is HBOT, and why might it be helpful?

An HBOT treatment consists of having the patient breathe pure oxygen in a chamber pressurized to two atmospheres. (If you're a scuba diver like I was many years ago, that's like going to a depth of 33 feet.)  For the Israeli study cited in the article, they first treated mice to find that their memory and cognition improved after treatment.  This had been done before.  But they also took six elderly patients with significant memory loss and exposed them to 60 treatments over three months.  The treatments consisted of 90 minute sessions, with five minute breaks every 20 minutes.

So how did that go?  First, the researchers detected a definite increase in delivery of oxygen to the brain.  They also found that the treatments led to a decrease in the presence of amyloid plaques, where the number  of amyloid plaques were increasing in the control patients.

Great.  Aduhelm reduces amyloid plaques.  But what happened with memory and cognition?  At the outset of the study, the patients actually scored a little better than the general population in cognition, but much worse on memory.  After the treatments, the patients showed some improvement in cognition, but much their scores were much better -- near normal -- for memory.  Very good.

The researchers believed that HBOT caused structural changes in blood vessels. This increased cerebral blood flow, reducing brain hypoxia and improving cognitive performance. They further believe it holds promise for the prevention of Alzheimer’s disease because it not only addresses the symptoms but also targets the core pathology and biology responsible for the advancement of Alzheimer’s disease. 

I will be very interested in hearing what my neurologist has to say about this.

Dr. John Trojanowski, 1946-2022

Dr. John Trojanowski, pioneer in the field of research on neurodegeneration and advocate for physical exercise to fight Alzheimer's disease, died on February 8.  He is well known for his discoveries explaining the role of tau protein in several neurodegenerative diseases and for correlating Alzheimer's disease with Lewy body dementia.  While he didn't dismiss the amyloid hypothesis for Alzheimer's disease, he did not believe tau got the attention it deserved.  (We discuss the tension between the amyloid hypothesis and tau in Beating the Dementia Monster.)

Trojanowski was an advocate for lifestyle changes to fight Alzheimer's disease.  In this 2012 video (9 minutes), he goes through each of the vehicles I've collected in "the Dementia Toolkit" and explains their power.

Dr. Trojanowski will be very much missed.