"Paradoxical Lucidity" -- dying patients with severe dementia suddenly regain lucidity and communications

The idea that someone with severe dementia would suddenly regain both lucidity and speech just before death seems terribly strange and challenges our understanding of how the brain functions when afflicted by disease.  There has been no systematic study of this phenomenon, but examples have been widely reported anecdotally.  An article in this weeks issue of Alzheimer's and Dementia the Journal of the Alzheimer's Association provided a survey of reports of such events and discussed their significance.  The article was "Paradoxical lucidity: A potential paradigm shift for the neurobiology and treatment of severe dementias." 

The article took the reports seriously and considered them likely related to near-death experiences.  It also considered that studying the phenomenon may find that AD is not completely irreversible.  

The article did not attempt to discern any new understanding about the phenomenon, but it discussed how a serious investigation should be conducted.  It also discussed insights that such an investigation might provide with respect to how the brain functions and what AD actually does to it.

This reminded me of something I'd seen recently regarding "functional MRIs" of the brain.  These produce the images you see of brains with colors denoting the level of neuronal activity in various regions.  However, what the MRI is actually measuring is blood flow and also oxygen content of the hemoglobin.  When neurons are "firing" they need extra energy and so need more glucose from blood.  Blood flow is increased in areas of neuronal activity.  It's like a microprocessor in your computer that needs more electrical energy when it works harder, and you can hear the cooling fan speed up as the computer works harder.  Increased blood flow is then a proxy for neuronal activity.  The computer can help us visualize what's going on with the neurons by adding color to areas with varying blood flow.

What I saw recently was work with people whose brains had no electrical activity -- they were "brain dead."  However, a functional MRI would still detect changes in blood flow within the brain when complete, meaningful sentences were spoken to the person.  But blood flow would not change when the same words were spoken to the person in a nonsensical sequence.  The assumption is that the parts of the brain that take in audio signals and interpret them no longer function, but somehow the brain is still trying to do that.  To some this suggests that, while the mind is intimately interconnected with the brain and is involved in brain activity, it nevertheless has a separate existence from the brain.  Is that what it means?  I'm not sure what to make of it. 


  

That afternoon snooze signals Alzheimer's...

We know that there's a role for sleep in Alzheimer's disease, and we promote getting good sleep as a way of trying prevent the disease or perhaps to fight it.  So what's the significance of napping during the day?

This weeks issue of Alzheimer's and Dementia the Journal of the Alzheimer's Association carried an interesting article about research that found a link between napping and developing AD.  The bottom line:  Older men who nap are more likely to develop AD.   In fact, men with longer napping duration had greater cognitive decline and higher risk of cognitive impairment. Men who napped for more than 120 min/day (vs. less than 30 min/day) were 66% more likely to develop cognitive impairment in 12 years.  The final conclusion was, "Napping might be useful as an early marker of cognitive impairment in the elderly, and its cognitive effects may differ by nighttime sleep."

So ... if you control your napping, does that reduce your risk for developing AD?  I wouldn't count on it.  A wise person once said, "Correlation does not imply causation." 

The study was "Objective napping, cognitive decline, and risk of cognitive impairment in older men."  "Objective napping" (as opposed to "subjective napping") refers to measuring sleep patterns with instruments.  Subjective napping refers to measuring napping by keeping a log. 

News on the Amyloid-Tau Dynamic

When Alois Alzheimer used a microscope to examine the brain of the deceased Auguste Deter in 1902 he observed what we now call "plaques and tangles."  These were a consequence of the two unusual proteins and fragments that characterize AD: amyloid plaques and collapsed microtubules.  We have discussed these plenty of times before.  The amyloids form when the "amyloid precursor protein" is cut by some enzymes (for unknown reasons).  The microtubules collapse because of the presence of an aberrant form of tau protein that's supposed to be holding the microtubules together.  So doctors and researchers may look for these substances in cerebrospinal fluid as evidence of the progression of AD.

This week's issue of ALZForum carried an interesting article about research on the progression of AD.  This progression is described in this year's Alzheimer's Association Facts and Figures report, which we discussed earlier.  What the recent article discusses is research using serial PET scans to further refine the dynamic of how the disease progresses, at least from the standpoint of the accumulation of beta-amyloid and abnormal tau and how that relates to cognition.

The short version is that amyloid begins to accumulate for a long time before there is any outward evidence of trouble.  Eventually the abnormal tau begins to appear at about the same time as there is evidence of cognitive decline.  The tau spreads throughout the brain, possibly propagating the disease. 

By taking a series of PET scans over a period of time, the rate of change of amyloid and tau accumulation can be measured and correlated.  Increasing accumulation of amyloid appears to signal advent of the tau pathology, suggesting that the amyloid is somehow influencing it.  One thing interesting to researchers is how tau pathology accelerates.  They are also curious about what level of amyloid correlates with initiation and acceleration of tau pathology.       

More on "Diet for the Mind"

In yesterday's post on Dr. Martha Clare Morris's book Diet for the Mind, I discussed her research on diet and AD and the diet that came from that.  But her book was also good on the other domains we discuss here and in Beating the Dementia Monster.  She makes the point that, if you want to do something meaningful about your cognitive decline, you need to address all of the domains concurrently.

So in the first chapter she writes some about AD and the nature of AD as well as about some of the other causes of dementia.  She then discusses the domains of physical exercise, sleep, maintaining social connections, and maintaining a positive outlook on life.  As we do in Beating the Dementia Monster, she addresses the brain derived neurotrophic factor (BDNF), and she discusses why aerobic exercise is so much more effective than resistance/weight training.  On the other hand, she explains that strength training can be very effective in preventing falls.

Diet for the Mind

In Beating the Dementia Monster, we discussed the MIND diet.  Research had found reduced incidence of AD among people who followed the Mediterranean and DASH diets, and the MIND diet was said to be an improvement on these.  In fact, in my post of March 6, 2019, I cited research that found no cognitive improvement with the Mediterranean and DASH diets, but improvement with the MIND diet.  But I have never gone back to the source when speaking to the MIND diet.  (I have, however, been following the MIND diet myself for about two years.)

This weekend, I finally read Dr. Martha Clare Morris's book, Diet for the Mind.  It was Morris who created the MIND diet to explicitly include nutrients known to support brain function.  In her book she describes the thought processes that went into its development and discusses the research that led to her formulation.  The second half of the book was devoted to recipes developed by her daughter.  The book answered a lot of my questions about the diet and the logic behind its composition.

One thing I wondered about was her exclusion of red meat, since I understood from the Wikipedia and Dr. Mark Hyman's book, Food: What the heck should I eat, that saturated fat, especially saturated fat from red meat, had been effectively ruled out as a nutrition issue.  Hyman had cited several studies that discounted cardiovascular risk due to intake of saturated fat.  But Morris cited research that claimed the opposite. She called one of the most important studies "seriously flawed."  So the MIND diet rules out red meat and keeps saturated fat to a bare minimum.  Hyman, nevertheless, discourages meat consumption in general.

Morris points out that her diet is the subject of a large study intended to definitively establish the place of the MIND diet as an effective weapon in the battle against neuro-degenerative diseases.  Is it a game-changer?  Results are due out in April 2021.

Stepping Back on Balance

In yesterday's post, "Two Steps Forward, One Step Back," I discussed a hiccup in my cognition that, for now, seems to have passed.  It was deeper and lasted longer than my previous hiccups, but things seem to be well now.  However...

I did not mention that part of the hiccup was a new issue with balance.  Since the very beginning (2013 or earlier) I have had a problem with balance.  In fact, this was the first sign that something was wrong.  My vestibular system (inner ear) was tested twice, but nothing was found wrong there.  That suggested that something was wrong with my brain.  Subsequently, I learned habituation exercises that re-train my brain and give me stability for several days at a time.  But in May of this year, at the same time I began having new cognition problems, I also began having a new problem with balance.

The new problem feels different from the problem that I had already been experiencing.  My sense is that the new balance issue is superimposed over the original problem.  When I do habituation exercises I still sense relief for the original problem but not the new one. Fortunately, both problems only manifest when I am standing or walking, not when I'm sitting.  And now when I'm driving.

Balance has actually been one of the most unpleasant parts of my experience with this disease.  When the habituation exercises have been ineffective, or their effects are wearing off, I feel quite unwell.  Not quite nauseous, but almost.  I think this is a side of the disease that most people don't understand, because they only think about memory loss.  On the other hand, I've read research papers indicating that it's a minority of us with AD who experience significant balance issues.  

The original problem usually made me feel intoxicated.  One question I was asked in neurological screening was "Do you ever worry others will think you are drunk?"  (I answered in the affirmative.)  The new problem does not make me feel intoxicated, but it definitely disturbs my gait, even more than the original.  In fact, it disturbs may gait quite a bit to the point of being quite unsettling.

It goes up and down.  A couple of days ago it wasn't a problem, but yesterday it was pretty bad.  And then, today, it's not bad at all.  I'm not sure what tomorrow will bring. 

One more thing to discuss with my neurologist on July 1.

Two steps forward, one step back

I will be seeing my neurologist in Seattle on July 1 for my annual evaluation.  This year she had me skip the annual psychometric testing, because I was doing so very well.  My scores have risen gradually but steadily since 2015, so giving it a rest might tell us something.  In 2017 and 2018 I was tested exhaustively by Harborview and a couple of different studies, so I had been getting pretty good at their tests which can distort results.  But I knew from my own subjective experience that I was holding my own or continuing to improve regardless of test results.

Ahead of the visit, I have been preparing a short account of what has occurred over the past year.  This has gotten me thinking about a number of things.

At last year's evaluation I told her that sometimes it seemed like something would break in my brain, and I would have a sudden apparant loss of cognitive ability.  However, these episodes seemed to pass, perhaps because my brain was adapting to whatever went bad.

At the end of April of this year, I was confident that, were I tested, I would score just as well as I had last summer.  By mid-May that had all changed.  I had another episode of losing ground, but this one was deeper, and I thought I might not recover.

There are two tests that I have been giving myself daily since 2016.  One is, do I remember to lock my car when I go into the gym?  The other is, can I recall that I checked for pedestrians and cars going straight after I turned left at the tricky intersection by the gym?  This had been the site of a couple of close calls in 2015 that led me to quit driving for 6 months.

During the second week in May, when I left the gym and got to my car the doors were always unlocked.  This occurred even when I had been reminding myself to lock up just as I pulled into the parking space.  I could also not recall having been cautious after leaving the intersection.

In 2015, I had mood swings/depressive episodes four or five times a week, but these receded in 2016-2018.  I had one about six months ago, and probably not another one for six months before that.  But I had a couple of them in mid-May.  Not very deep, but enough to make me worry that I was going back to 2015.  This was deeply worrying.

I devised a new test for myself.  I found a "random noun generator" on the internet that would give me five random nouns I could use for testing my memory.  In the Mini-Mental State Exam used for screening people for cognitive impairment, they give you a list of three words to remember, and then ask you to recall the words five minutes later.  (In 2015 I could only recall one of the words.)  In the Montreal Cognitive Assessment they ask you to recall five words.

So every second day, I order up five new nouns and have Amy write them on 3X5 cards without me seeing them.  I review the cards two times and then distract myself for five minutes, usually be reading a magazine article.  How many of the words can I recall?  Usually 3.  Once all five, once only one.

This is really, really unscientific, and it doesn't tell me where I'm at.  I do hope that it will show trends, but I probably don't self-administer in a way that ensures consistency.  So I'm not even sure about the trends.

But I have gained confidence that I am still doing better now than in 2015.  I locked the car door every day this week, and I'm confident that I have been safely turning left at all intersections.  I don't think my card trick is pointing to any nasty trend, and the time of the mood swings seems to have passed.

Life is good.