Slow News -- for Now

Of late, I've been struggling a bit to find material that I thing everyone here would find interesting.  I haven't heard of any new breakthroughs in Alzheimer's research, and there's nothing much new with me.  (Good news.). And no new scandals.  (Also good news.)

But this will change.  The first week in March is when the Alzheimer's Association normally releases their annual Facts and Figures Report.  This is always loaded with new insights coming from research, as well as revelations that researchers have been sitting on, waiting for the big moment.  So stand by.

When someone has something substantial to announce, they want to do it when it will get the most exposure.  Important conferences are the best place to do that.  And the most important conference in the world of Alzheimer's research is the Alzheimer's Association International Conference.  This year it will be held in Toronto during July.  So expect interesting things to materialize then.

I have been a little distracted making videos for the Dementia Monster YouTube channel.  Click here.  A lot more effort goes into making a video than a blog post, but my first priority is this blog.  For one thing, there are a lot more subscribers to the blog than the YouTube channel.  (So thank you.)

When I get the Facts and Figures Report, you'll be the first to hear what I find interesting in it.

Social Activity Stalls Dementia -- Really

Tool #2 in the Dementia Toolkit is "Maintain or Increase Social Activity."  But is there a scientific basis for assigning importance to social activity?  Absolutely, and the supporting evidence is getting stronger.

In Beating the Dementia Monster we said that I had met an Alzheimer's researcher, a neurologist with a practice of 22 years, who said that in his experience the most powerful lifestyle factor in brain health is social connection.  When I said I'd heard that physical exercise is most important, he said that people who go to the gym with a friend do much better.

I had a friend named John with dementia.  Our wives were friends, and I didn't meet him until he was already in serious decline.  Eventually he moved into a memory care facility near our home, and I would go visit him pretty much daily.  He was a very pleasant person and easy to talk to ... even when he didn't make much sense.  He said he recognized me each day, but I'm not sure he did.  He  certainly didn't remember my name.

Over the time I visited John, I observed others in the same facility, few of whom had frequent visitors.  My very subjective judgement was that I could observe some of them declining, while John did not seem to decline further.

Until covid.  As soon as covid hit, the whole facility was locked down for a very long time.  Residents ate in their rooms and had no other social activity.  After a few months of this, John died.

I'm not a doctor, and I don't know much about how he was treated for his dementia.  But I am sure that he would have lived a lot longer if his social activity hadn't been cut short.

Which brings me to an interesting study published in the journal Alzheimer's and Dementia, the journal of the Alzheimer's Association.  It was entitled, "Late-life social activity and subsequent risk of dementia and mild cognitive impairment."  The researchers found that maintaining social activity delays the onset of dementia by an average of five, precious years.

Here's another article on the subject.

The research was done at Rush University, where the MIND diet was developed.  They studied 1,923 older adults over a period of seven years, measuring their social activity against changes in cognition.   Social activities they measured included going out for meals, attending sporting events, playing bingo, taking day or overnight trips, visiting relatives and friends, attending religious services, and doing volunteer work.  They controlled for age and physical health.

The researchers noted that 5-year delay in the onset of dementia is worth about $500,000 in health care costs. 

One thing they didn't control for was differences in physical activity.  They said it's possible, for example, that people who visit friends and family often may be more likely to get physical exercise.

So I go down the list of social activities they evaluated.  We don't go to sporting events or play bingo, but we certainly go out for meals (maybe too much?), go on plenty of overnight trips to visit family in Seattle and on the East Coast, attend religious services, and do volunteer work.  I'm an elder in our church, and I've been a volunteer at the food bank for eight years.  And the thing I find most rewarding at the food bank is just working alongside and socializing with other men my age.

So how much of my success is due to the gym versus my social activity?  Or, for that matter diet, fasting, managing stress, practicing Spanish, and sleep?  It's all in the multi-domain approach.  If you're serious, you'll do everything you can.  And it all works.

Get those plaques out early!

I think it's amazing how researchers have shown that you can actually clean the brain of those amyloid plaques we see in Alzheimer's disease.  This has been done with monoclonal antibodies that consume and dispose of the pesky peptides.  But what is the role of the plaques?  Are they a part of the disease process, such that removing them will stop the disease?  Or are they perhaps part of the body's defense against a pathogen causing the disease?  Or are they there for some other reason?

We have discovered that some treatments removing the plaques appear to slow, but certainly not stop the progress of the disease.  Others get rid of the plaques, but the disease continues.  Are there better approaches to removing the plaques that might more reliably improve memory and cognition?

One thought that comes up often is that we need to attack the disease earlier in its progress.  Generally, participants in drug trials are already showing evidence of cognitive impairment.  But, as we discussed in Beating the Dementia Monster, the disease has been in progress for at least 15 years before the first symptoms appear.  And so it's common to read a proposal that we need to start treatments much earlier.  But I haven't seen much success in that area ... until recently.

"Dominantly Inherited Alzheimer's disease" (DIAN) refers to what we called in Beating the Dementia Monster "young onset" Alzheimer's disease.  (We avoid the term "early onset" Alzheimer's disease so as not to confuse it with "early stage" Alzheimer's disease.)  We described the origin of the disease, specifically in the presence of three, relatively rare genes.  These are PSEN1, PSEN2, and APP.  When one of these genes is present in someone's genome, and if it is dominant over its recessive partner, the person carrying the gene is almost certain to develop the disease -- and develop it at a young age.  Usually, this is in the decade of the 50's, but it could even be in the person's 30's.  

This means that, through genetic testing, we can identify people at a very young age -- even from their childhood -- who are very likely to develop the disease .  This is more than that 15 years before those first symptoms.  So, if we can now identify those people, how about starting to administer the treatment at the very beginning of the disease process -- or even before it begins?

That's what they're doing at Washington University, St. Louis.  In a series of three trials, they are trying to stop the disease before it begins or else to interfere with it's progress once it has begun.  The first trial is using the monoclonal antibody "remternetug" to remove the plaques.  They are enrolling participants as young as 18, perhaps 25 years before the expected onset of the disease.  Expectations regarding onset are based on what happened with the participants' parents. 

According to the Washington University web site, "the trial is part of the Knight Family Dominantly Inherited Alzheimer Network-Trials Unit (Knight Family DIAN-TU), a clinical trials platform designed to find medicines to prevent or treat Alzheimer’s disease."  ("TU" signifies "trial unit.")

The researchers hope to enroll 240 participants in the prevention trial, and the participants will receive the antibody treatments for two years.  They plan to start reporting results relatively soon after the first participants complete their two years.  They will be looking for evidence they have obstructed the disease, although it will be way too early to see if the treatment affects memory and cognition.  That will take years of follow up.

So is this it?  Is this how we will establish a pharmaceutical resolution to this terrible disease?  We won't know anytime soon.  If it is effective, and if it's equally effective with other "flavors" of the disease, it will still be a project to determine who will benefit from it.  Certainly the presence of the ApoE4 gene (the one they look for in 23&ME) in someone's genome would indicate this is a promising treatment.  And there are at least 30 other genes that predispose someone to the disease.  So genetic profile will be a starting place.  But don't be holding your breath for any near-term benefit.

Wrong Temperature in the Home = Worsening Dementia

Can ambient temperature in the home affect cognitive performance in seniors?  So it appears.  According to a new study, a 7 degree F (4 degrees C) variation either way from an optimal band results in doubling cognitive difficulties in test participants over 65.  And what's the optimal temperature range to preserve memory and cognition?  It's 68-75 degrees F, or 20-24 degrees C.

When I read this, I thought, "Isn't everyone's home like that?  Mine is."  But last winter we had more than a week of single-digit highs.  And a couple of summers ago, we set a local record of a three or four weeks with triple-digit highs every day.  During the summer, I needed the HVAC guy to come over and get our system to work properly.  I could afford that.  Can everyone?

When we first moved here, everyone had swamp coolers to cool their homes.  From my observation, they worked OK when temperatures got up into the 90s in our very dry (steppe desert) climate.  But I don't know about when it gets up to 112F or so.  We hit 118F about four years ago.  So keeping in that ideal range could be hard for a lot of folks.

One of the most important factors in preventing and controlling Alzheimer's disease is sleep.  The Sleep Foundation says the ideal temperature for sleep is 65-68F.  They say you should keep your bedroom there.  I've read some experts who say 68F is the target value, which would put you at the low end of the range identified in the research.

I tried keeping our bedroom at 68F, but my wife couldn't sleep with it that cold.  So I keep it at 70F at night.  Seems to work OK for us, although I continue to have problems with insomnia.

So how did they do this research?  It was published in the Journals of Gerentology, Series A, as "Home Ambient Temperature and Self-reported Attention in Community-Dwelling Older Adults."  It was a longitudinal study, meaning they relied on surveys to analyze what happened with different populations.  They monitored the temperatures in the homes of 47 adults, aged 65 and older for a year, using the surveys to measure perceptions of difficulties in keeping attention.  So, the data was self-reported, and not the result of any cognitive tests. 

Here's some more reading on this research.

I'm guessing they had instruments in the homes to track temperatures, and the temperatures were those preferred by the test participants.  How accurate were the reports of cognitive difficulties?  Your guess is as good a mine.  But the researchers said that this study was a "proof of concept" indicating that they or someone else should do a randomized control trial to investigate this phenomenon more deeply.

But I'm a little frustrated.  I see one promising "proof of concept" study or some other exploratory study after another where they say "more research is necessary."  But I never seem to see the more research that was necessary.  Why not?

Huffing Xenon gas to treat your Alzheimer's...

Xenon gas is one of the chemically inert, or noble gases, along with neon, argon, helium, radon, and krypton.  So, if it's chemically inert, you'd think that it would have no biological effect in the body.  But, it turns out that's not the case.  Inhaled xenon has long been used as an anesthetic -- meaning, it can interact with the nervous system.  More recently, researchers have been exploring its property as a neuroprotectant in cases of hypoxia and traumatic brain injury.  So would that apply to the injury to the brain caused by Alzheimer's disease?

Well, at least in mice, the answer seems to be yes.  And it seems to do this by changing the behavior of microglial cells in the brain to stop them from causing inflammation.  We discussed microglial cells and their likely role in Alzheimer's disease in Beating the Dementia Monster.  Microglial cells are central players in the brain's unique immune system.  Microglia cells cause inflammation, because inflammation helps to protect damaged tissues.  But when poorly regulated, inflammation also causes damage itself, and much of our effort to control Alzheimer's is directed at tamping down inflammation.

Mice that had been bred to have a brain disorder mimicking Alzheimer's disease were placed in a chamber containing an atmosphere of 30% xenon gas and 21% oxygen -- the same oxygen as in regular air.  I guess the remaining 49% was, like our normal atmosphere, nitrogen.  They were exposed to this atmosphere for 40 minutes.  Their microglia were examined after intervals of 3, 7, and 14 days. 

Inhaling xenon gas by mice lowered amyloid plaques and reduced neurodegeneration associated with that tau tangling.  The researchers went so far as to insert some human brain tissue in the brains of some mice (no, I don't know how they got it), and they found that what worked with mouse brain tissue also worked with human tissue.  So, in the vernacular of the drug culture, it's now time to get some humans to huff xenon and see if this works in people.

The research with "mouse models" was published in the journal Science Translational Medicine.

You can read more here, but it gets a little deep for most of us.

One Million Cases of Dememtia per Year by 2060!

There's a new study projecting that, by the year 2060, we will be getting a million new cases of dementia each year.  The researchers conducting the study calculated that adults over the age of 55 have a 42 percent average risk of developing dementia within their lifetime.  Past studies had put the risk at up to 14 percent for men and up to 23 percent for women.  That's a huge jump!

Why will that be happening?  Well, baby boomers will be getting older, but here is my editorial opinion: Only approximately 20% of US adults are meeting recommended lifestyle and cardiovascular health targets.  And cardiovascular health targets are Alzheimer's disease prevention targets!  You know -- eat right, get enough exercise, don't smoke, address hearing loss.  That kind of stuff.  When people don't hit their targets, the incidence of Alzheimer's disease goes up.  And up.

In Beating the Dementia Monster, we discussed what seemed to be an emerging trend of declining cases of dementia.  This was believed to be a consequence of significant advances in steps to improve cardiovascular health and prevent heart attacks.  But according to this new research published in the journal Nature Medicine, that's not what we're anticipating any more.  (If that link doesn't work for you, here's an article from Smithsonian Magazine with a link in it that should work.)

The researcher's hailed from some of the most prestigious institutions studying dementia in the United States.  They drew their data from a large, earlier study of heart disease that provided health and lifestyle data for about 15,000 subjects, "The Atherosclerosis Risk in Communities Study."  Data went back to 1987.  The new dementia study included the following statements: "The lifetime risk of dementia after age 55 years was 42% ...  Rates were substantially higher in women, black adults and APOE ε4 carriers, with lifetime risks ranging from approximately 45% to 60% in these populations.  The number of US adults who will develop dementia each year was projected to increase from approximately 514,000 in 2020 to approximately 1 million in 2060.  The relative growth in new dementia cases was especially pronounced for black adults."

And, "[M]ore than four in 10 adults developed dementia in this large, longstanding, community-based cohort study, with higher rates in APOE ε4 carriers, women, and black adults.  Approximately 1 million US adults will develop dementia annually by 2060.  Policies that enhance prevention and healthy aging are urgent public health priorities for reducing the substantial and growing burden of dementia."  Yep.

A New Way to Live to 150?

Many years ago (40 years?), I began seeing articles in popular media about extending your life simply by eating less -- "caloric restriction" they called it.  It was noted that mice, yeast, and monkeys all lived longer if they consumed less calories -- sometimes what seemed like starvation level caloric restriction.  What was attracting attention were people doing extraordinary things to reduce their caloric intake (starving themselves) in the hope that they'd live to (as I read one man say) 150.  This phenomenon has been studied, and there is peer reviewed research (like this) about how that might work.

This suggests that anorexic people should live longer, but I wouldn't call that a good plan.  It may, however, relate to why intermittent fasting has such a positive effect on the chronic diseases (like Alzheimer's) that too often characterize old age.

I very often read about and hear from people wondering if there might not be a pill you can take that would do the same thing that fasting, dieting, and exercise do for the brain.  Well, there's a new candidate for something that might do that.  And not just the brain, perhaps every aspect of aging.  There's a "bile acid" called lithocholic acid (LCA) that might do it.  That's according to a research team at Xiamen University in China.  The acid apparently works by activating the metabolic master regulator AMP-activated protein kinase (AMPK).  Makes sense, right?  (If you figure that out, please let me know.) 

According to the researchers, significant caloric restriction  in people appears to improve metabolic health and markers of aging, even when people are not overweight to start with.  Tests with mice on Alzheimer’s disease suggest caloric restriction suppresses production of amyloid and tau and speeds removal of amyliod from the brain.  In us older folks, caloric restriction benefits working memory and processing speed but perhaps at the expense of our ability to conduct tasks that rely on good hand-eye coordination and cognitive flexibility.  But this means starving all the time and losing muscle mass, so it's not a good idea for most of us. 

According to this research, bacteria produce LCA in the small intestine when they break down primary bile acids.  LCA emulsifies fats to render them digestible.  But LCA can also be absorbed into the blood like other fatty acids produced by the microbiome, some of which improve the health of the brain.  

Remember the gut-brain axis?  Some really weird stuff goes on between the bacteria in your gut and your brain.  So take care of those bacteria.  (Eating beans and fermented foods, like kimchi, can help with this.  Some would add yogurt.  But aspartame and sucralose can be hard on the gut biome.)  

The scientists added LCA to the drinking water of some well-fed mice, and it activated AMPK in their skeletal muscles to the same degree seen in calorie-restricted mice.  While it didn’t extend their lifespans, it did boost their vigor: Old mice that ingested LCA ran farther on a treadmill and gripped a pressure-sensing bar harder. Their insulin sensitivity and glucose tolerance were better, and their muscles recovered faster after damage.  My reaction to this that, despite the promises, feeding people LCA may not actually extend your life.  But it's still improving important markers of Alzheimer's disease, notably insulin sensitivity and glucose tolerance.

So it seems like there's something here.  But all of these breakthroughs we keep seeing are frustratingly far from becoming reliable treatments.