I'm out of the woods, but news on declining dementia rates

First, I want to thank those of you who sent messages of support during my recent adventure with sepsis and kidney stones.  It appears that this week my doctors and I will be wrapping it all up.  Life goes on.

And something else interesting has come across my screen regarding how it is that dementia rates are declining as we discussed in Beating the Dementia Monster.  Spoiler alert: New research has partly supported some of the speculation in my book.

In the very last section of the second edition, "Good news/Bad news," I said that Alzheimer's disease rates in Western countries has actually been declining over the past 25 years despite an aging population.  I said that perhaps this was due to placing a lot of emphasis on reducing cardiovascular risk factors.  We noted that doctors like to say, "What's good for the heart is good for the brain."  And so there has been a significant reduction in cigarette smoking and an increased use of drugs to control blood pressure.  I'd like to say that people have lost weight, are eating better, and are exercising more, but that may not be true.  Nevertheless, the incidences of both cardiovascular disease and dementia have fallen together.

There is a new study on this published in the February 20 edition of JAMA Neurology, "Trends in Postmortem Neurodegenerative and Cerebrovascular Neuropathologies Over 25 Years."  The study examined the 25-year trends in incidence of dementia and trends in cardiovascular disease, confirming their consistency.  But they came to a conclusion a little different from mine.

I speculated that it was Alzheimer's disease that was declining, when they concluded that it was dementia that was declining.  Even when members of the cohort of 1,540 subjects had less dementia, they still had no decrease in the amyloid plaques and tangles that characterize Alzheimer's disease.  This was determined through autopsies of all test subjects.  (We said in Beating the Dementia Monster, the final confirmation of Alzheimer's disease is in the autopsy.)

So what's the takeaway here?  If you're like me, and you're told that you have Alzheimer's disease, you can still stave off dementia through lifestyle changes.  You will likely still have Alzheimer's disease, but you can at least delay the accompanying physical and mental decline of dementia.  These are lifestyle changes that fight cardiovascular disease and metabolic syndrome (including diabetes).  This is exactly what we designed The Dementia Toolkit to do.

I'm not out of the woods ... but what's with them nuts, anyway?

So I'm off of the antibiotics, but an ultrasound and a CT scan tell us that I still have two large kidney stone fragments to deal with.  One is in the ureter and will likely come out when they remove the stent.  (Yes, there's still a stent in there.)  The stent is sized to allow the fragments to pass around it while urine passes through it.  The largest of the two fragments is trapped between the outer wall of the stent and the inner wall of the ureter.  The other fragment is still stuck up in my right kidney.

So Wednesday I go back in for surgery with general anesthesia.  The plan is to pull the stent and then send up a laser to zap the fragment that's still in the kidney.  Then they'll put a stent back in to allow the fragments to pass.  What's on my mind is the possibility that more invasive procedures invite more infection.

This all began with over-consumption of spinach and almonds.  Both are good for your brain, but both also contain lots of oxalate.  The oxalate is the material of the type of stone that got me.  So my doctor said don't eat that stuff.  I stopped both, but with some substitutions.  Broccoli, asparagus, cucumber, tomato, blueberries, strawberries and avocado are reasonably low in oxalate, and so these go into much of the vegetable portion of my diet.  

But what about the nuts?  Is the oxalate problem the same for all nuts, or is it peculiar to almonds?  From what I read, almonds are a particular problem for oxalate, but walnuts are not.  I like to mix walnuts with blueberries and eat them like a dessert.  I feel comfortable with this.

But how good are walnuts for brain health?  Are they as good as almonds?  We know that tree nuts are good for the brain.  What does the research say about almonds vs. walnuts?  Turns out there's a brand new study to help answer this question.

The study is called "Impact of Nut Consumption on Cognition across the Lifespan," and it was published in the journal Nutrients.  Here's a summary article from News-Medical.net.

What the researchers set out to do was measure the influence on cognition of nut consumption prenatally, on younger people, and on the elderly.  They did this by performing a meta-analysis of 15 peer-reviewed papers on the influence of nut consumption on cognition.  The analysis also sought to discern which nuts had the most positive effect.  They found that nuts in general were helpful, but walnuts were the best.  However, not all the papers found a positive effect from nut consumption, and the effect was sometimes weak in those that did.  I didn't see any explicit mention of almonds at all.  They concluded:

"While limited and inconclusive, available evidence suggests a possible role for nuts in the maintenance of cognitive health and prevention of cognitive decline in individuals across the lifespan, particularly in older adults and those at higher risk.  Walnuts, as a rich source of the plant-based polyunsaturated omega-3 fatty acid alpha-linolenic acid, are the nut type most promising for cognitive health.  Given the limited definitive evidence available to date, especially regarding cognitive health biomarkers and hard outcomes, future studies are needed to better elucidate the impact of nuts on the maintenance of cognitive health, as well as the prevention and management of cognitive decline and dementia, including Alzheimer disease."

So it appears that walnuts are even better for brain health than almonds.

A tough couple of weeks...

Most of you haven't heard from me recently because I've been pretty much out of commission.  You know that I had a kidney stone procedure, but I subsequently was hospitalized with sepsis.  Last Wednesday, I really thought I was going to die.  I'm thinking one or more of the medical professionals attending me thought the same.  I had plenty of prayer support from friends and family, and the medical professionals did a wonderful job with modern technology.  So I'm still here.

Unfortunately, this seems to have come about by my injudicious application of the MIND diet.  I think I overdid it on the spinach and almonds, two of the worst things for kidney stones.  But I'd never had a kidney stone before, and I didn't anticipate this kind of problem.  So walnuts are now doing fine for my tree nuts, while asparagus, broccoli and other green, leafy vegetables can fill in for the spinach.

I was hospitalized for seven days, coming home on Tuesday.  The infection was from a very nasty, highly resistant bacteria called enterococcus.  

I continue to take antibiotic infusions at home 3X/day.  They ran what they call a PICC line from my upper arm to a vessel near my heart.  Then they have an IV arrangement like in the hospital for the medication to drip down to the line.  It drips about a drop/second, taking about 45 minutes for one dose.  This should continue at least until the 10th.

The problem is that we're not done.  They blasted the jumbo (17mm) kidney stone back in mid-December, but there were still some pretty large stone fragments.  They said that I should be able to pass anything up to 6mm, but then one fragment came out that I measured 8mm.  But it turns out that there are more.

When they did the first procedure in mid-December, they inserted a stent.  The stent provided a pathway for urine from the kidney to the bladder, while stone fragments would be able to pass around the stent.  But not many did.  So they pulled the stent out in mid-January, and we got a large flow of stone fragments.  But a CT scan showed that not all  came out, including one big one.

So they put me out again and put in a new stent.  The infections seems to have arisen from that procedure.  We are breathing a sigh of relief that this infection is over, but we remain anxious about going back in to recover the second stent.  That's currently scheduled for February 22.

Finally time to dump the amyloid hypothesis completely?

As we describe in Beating the Dementia Monster, it was Alois Alzheimer who first saw amyloid plaques and tau tangles in the brain of a deceased seamstress and hausfrau, Auguste Deter.  Since then, our focus on trying to understand the disease has been on the phenomenon of these two markers.  The conventional wisdom has been that if we can just control them, we will be controlling the disease.  If we can get rid of the amyloid plaques, we can control the disease.  If we can stop the generation of the tangles, we can control the disease.

But our experience has now shown that if we get rid of the plaques, we have neither stopped the disease nor cured it.  Yes, we can (apparently) slow it down with Aducanumab and Leqembi, but it will still get you in the end.

As we said in Beating the Dementia Monster, maybe the amyloid plaques actually have a purpose, and trying to get rid of them is the wrong thing to do.  We noted some experts believe the plaques are actually there to protect brain cells from microbes and toxins, such as p. gingivalis, the bacteria that causes gum disease.  Some researchers have been pursuing this hypothesis, but they haven't been getting headlines the way the more easily grasped amyloid narrative has.

One of the more popular and productive health YouTubers is Dr. Eric Berg.  He's a chiropractor who is very big on keto diets and intermittent fasting.  He takes sometimes serious heat from critics about the accuracy of some of the things he says on his videos, but he has a lot of followers and material.  I don't search out his viewpoint on health matters, and I take what he says with the proverbial grain of salt.  But the YouTube algorithm seems to think I should be watching all of his stuff.

Regardless of other baggage, I thought a new video captures some important elements of the shifting landscape of Alzheimer's research.  It fits with authoritative information that I've seen elsewhere and that we provided in Beating the Dementia Monster.  The video is here.

In the video, Berg explains what's wrong with the amyloid hypothesis and gives a rationale for how lifestyle changes can prevent or stall Alzheimer's disease.  He likens treating amyloid plaques to trying to put out a forest fire by putting out the match that started it.  In his discussion, he had a novel way of describing the brain's unique immune system which is separate from the system that serves the rest of the body.

One thing that disturbed me was a blanket conclusion that people with Alzheimer's disease should begin a radical daily fast, eating only one meal a day.  As we discussed before, intermittent fasting is not recommended for the elderly.  If you are older and you want to fast, talk to your health care provider first!

I'd better say this!

I have been doing a pretty radical daily fast since 2020, and I'm now 73.  You should understand that intermittent fasting is not recommended for the elderly.  Some say you're elderly when you're over the age of 65 with functional impairments or if you are otherwise over the age of 75.  But it depends on who you ask.  As I understand it, the concern is that elderly people have more trouble getting all of their nutrition, and fasting will impair that further.  This is why we have products like Ensure.  (People with eating disorders also should not fast.)

What I'm trying to do here is tell what I've done and what my experience has been.  I underscore these with stories about research and news on brain health.  In Beating the Dementia Monster, I warn strongly against starting an exercise program if you are over 50 and haven't consulted with your doctor.  I have consulted with both my primary care provider and neurologists concerning both my exercise and my fasting.  They have asked some questions, but they haven't discouraged me from doing these.  And I'm not having trouble getting all of my nutrition.  Even with the fasting, it's still a fight to keep my weight where I want it.

Nevertheless, older people must consult with medical professionals about both fasting and exercise!

A new twist on exercise, intermittent fasting, and BDNF

If you read Beating the Dementia Monster, you know research shows that exercise affects the progress of Alzheimer's disease, and it may even be able to prevent it.  (No one claims it cures it.)  The conventional thinking is that exercise prompts generation of a protein called the brain-derived neurotrophic factor, or BDNF.  BDNF has the ability to repair damaged brain cells and to prompt the formation of new neurons from stem cells.  

In 2018, we cited peer-reviewed research showing that about 400 minutes of exercise per week was optimal for impeding the progress of Alzheimer's disease, although the research said nothing about the relative intensity of the exercise.  (This led me to my current regimen of 55 minutes per day on the treadmill, six days per week.)  But the research never said how intense the exercise should be.  To get the results of the 2018 research, is walking around the block a few times enough, or must you run full speed the whole way? 

In 2020, we also cited research published in The New England Journal of Medicine stating that intermittent fasting would also encourage the generation of BDNF.  My review of what people were saying on the Internet (not a very scientific approach) found that the conventional wisdom was that a 20 hour/day fast would produce enough BDNF to be effective.  But is that true?  In any event, I've been following a 20 hour/day fast now for three years.  Some days it's more like 19 hours, but I only break the rhythm for special occasions.  (It's also hard to keep that schedule on Fridays, when Amy and I go out for lunch and do our shopping.)

My experience very definitely tells me that getting physical exercise has profoundly influenced the progress of my disease.  But I have no clue about whether the fasting has done anything.  I believe that I had largely "caught up" with normal aging by 2019 and wasn't expecting further improvement in 2020 when I began fasting.  And I have no control to compare to -- I have no twin who did the opposite of me that I can compare results with.  So who knows?  I keep fasting, because I don't want to rock the boat if it's working.

So there are two big questions: How hard to you have to exercise to get results, and does a 20 hour fast really affect the progress of neurodegenerative disease?  As it turns out, there is some interesting new research that tries to answer both questions.  However, it only tries to answer the questions from the standpoint of how much BDNF is generated.  As this article explains, intermittent fasting affects the brain in several ways other than through the production of BDNF.  Exercise, too, has positive effects beyond generation of BDNF.  Nevertheless, measuring what influences the generation of BDNF has a lot to say about how effective exercise and fasting are with respect to brain health.

I came across this research published in The Journal of Physiology that found 20 hours of fasting did little to increase the production of BDNF, but that six minute bursts of vigorous exercise did.  The six minute bursts were compared with 90 minutes of light exercise which did little.  The vigorous and light exercise were both bicycle riding.  Here's their press release.

Bear in mind that this was a small study involving only 12 subjects.  They were younger and not known to have any neurodegenerative disease.  Also, the research only measured production of BDNF.  It didn't measure the actual benefit to the brain from either fasting or different types of exercise.  Both fasting and exercise have important benefits to the brain beyond BDNF.

But I think it does tell us something helpful, particularly that the level of intensity of the exercise does seem to matter quite a bit.  I'm not planning to start doing 6 minute bursts of high intensity exercise, but the exercise I currently do is significantly more intense than the 90-minute bicycle ride they studied in the research.  It's 50 minutes on the treadmill at 3.5 mph at a 10-degree incline.  This is followed by a five minute cooldown at 2.5 mph with no incline.

All I can say is that, every morning when I wake up, I just can't believe it.  I remember back to 2015 when I was in free fall, and I thank the Good Lord for providing the wherewithal to battle this thing and hold it at bay.

Welcome Leqembi!

Yesterday, the FDA approved for use the monoclonal antibody (mab) treatment lecanemab (code named BAN2401) via their "accelerated approval process."  This is kind of like the process that got them in trouble with aducanumab, but I doubt they will face the same headwinds.  For one thing, their approval doesn't fly in the face of the advice of the Peripheral and Central Nervous System Drugs Advisory Committee.  You'll recall what happened with aducanumab.  

So now Biogen and Esai will market lecanemab as Leqembi.  How well will this go?  For starters, the wholesale price will be another $26,500 per year.  That doesn't include the periodic MRIs to check for brain swelling and microhemorrhages.  And did I mention three people died during clinical trials?  Oh -- yes I did.  What will the insurance companies say about paying for it?  What will Medicare say?  We shall see.

How do Biogen and Esai justify the price?  In this statement, they say it's based on the value of the treatment to society -- their concept of the "societal value of medicine" in relation to the "price of medicine."  If history is a guide, Elizabeth Warren and a few others will offer their thoughts on how that should work.

While the "mabs," like Aduhelm and Leqembi, go beyond treating symptoms, we don't know that they are treating the cause (or causes) and mechanisms of the disease.  We just don't really understand those very well.  And so these are not cures, they simply slow the progress of Alzheimer's disease.

Will the pros outweigh the cons for many people?  If you slow the disease enough to add a few good years to someone's life, maybe so.