My Video on Molecular Biology

As I wrote earlier, I've run out of gas with respect to posting new insights on Alzheimer's research. But I'm still busy (and still OK). One thing I did was to post a YouTube video intended to update Baby Boomers on what's happened in the world of biology since we were in the 10th grade. It's relevant to an understanding of recent revelations in Alzheimer's research. You can see it by clicking here. 

It does dig fairly deeply into molecular biology, and it's likely to go too deep for many of you. Also, I have some questions about how all of this makes sense, and I may disappoint some of you in where I go with it. Here is the index:

Chapters 00:00 - 02:22 - Introduction 02:23 - 06:20 - On the philosophy of science 06:21 - 08:52 - Religion vs. science 08:53 - 10:40 - Biology - Then and now 10:41 - 14:15 - Organelles and the cell membrane 14:16 - 18:13 - DNA - What is it, what does it do? 18:14 - 19:07 - Prokaryotes and eukaryotes 19:08 - 23:12 - DNA replication 23:13 - 26:32 - Mitosis 26:33 - 27:57 - Meiosis 27:58 - 29:25 - Charles Darwin on how evolution proceeds 29:26 - 34:23 - The Central Dogma and protein synthesis 34:24 - 41:38 - Energy processing in the cell 41:39 - 44:50 - Cellular respiration 44:51 - 45:17 - Utilization of energy within the cell 45:18 - 47:33 - The origin of life and the Cambrian Explosion 47:34 - 49:48 - Do the numbers add up? 49:49 - 50:23 - Gene regulatory networks 50:24 - 52:34 - Darwin's very dangerous idea 52:35 - 53:13 - The chicken ... or the egg? 53:14 - 54:14 - Evolution and sickle cell anemia 54:15 - 55:05 - Evolution and the Peppered Moth 55:06 - 58:36 - Hypotheses on how organisms might increase in complexity 58:37 - 01:00:20 - The universal acid 01:00:21 - 01:01:47 - Back to the Cambrian Explosion 01:01:48 - 01:02:08 - The work of an engineer? 01:02:09 - The bacterial flagellal motor

I'm Still Here

As I posted back in November, continually generating content for the blog has gotten to be too much of a burden.  While I am committed to updating you on any changes in my life (or, perhaps, lack of changes) relative to my story in Beating the Dementia Monster, I don't plan on commenting anymore about Alzheimer's news.  But I am hearing from folks wondering why I've been so quiet -- it's because nothing is really happening.

I am in a whole slew of research studies, and I get some feedback from them.  I recently had one MRI and one amyloid PET scan.  I'm supposed to have a tau PET scan sometime, but they haven't scheduled it yet.  It's been several months since the PET scan, and a month or two since the MRI.  They are in no rush to give me any feedback, so I don't expect to hear from them for some time yet.  But, based on my results from 2022 and how well I feel, I don't expect any surprises.  But I'll post when I do hear back.

When I told my neurologist in Seattle that I didn't see the point in coming back to her, she asked me to continue, but relax to coming once in three years.  So this fall will make 3 years.  That will include the full suite of psychometric testing.  I'll share the outcome of that.

Along with the MRI, I did have a scaled back -- but still intense -- set of psychometric tests.  Because it's for research, they don't tell me the results.  But I've taken enough of these to be able to tell when I've done well.  And I'm sure I did fine.

So Amy and I make it to the gym most days. We attend to our diets and stay socially active.  My biggest problem is sleep, and I'm lucky to get 5 and a half hours.  But my Fitbit tells me that I'm usually getting at least an hour of deep sleep.  As we said in Beating the Dementia Monster, deep sleep is most critical for Alzheimer's prevention and treatment.

If anything exciting happens, I'll post here.

What's Going on with Me

It's been a month since I last posted.  Is something going wrong with me?  No, I'm fine.  I guess that, after more than seven years and more than 550 posts, posting has become something of a chore.  My heart isn't in it as it was before.

Now, I'm not closing down the blog.  I believe I committed in Beating the Dementia Monster to at least keeping people updated on my case.  Does continuing my lifestyle changes have durability with respect to maintaining my memory and cognition?  Will (as some propose) my lifestyle changes use up all of the available stem cells in my hippocampus and revert me to an evolving dementia?  I want to know the answers as much as any of you!  So when I encounter new milestones, I'll share those.

At the moment, my sense is that my memory and cognition is consistent with healthy men my age.  This doesn't mean that things don't happen that cause me concern, but overall I think I'm fine.  My care team has not evaluated me for two years, and they say they won't test me again until a year from now.  I plan to share that outcome because it will say a lot about the durability of my strategy. 

In the meantime, I am participating in a number of research studies that test me, and I expect to get some kind of insights from them.  Yesterday, I had an amyloid PET scan that will say something about where my brain is at.  They tell me I can have the results in about 90 days.  Before then, I should also have a tau PET scan and another MRI.  Even though these are for research, the radiologist's reports are entered into my medical record, and I have access to them.  I also expect more psychometric testing for these studies.  So I'll share what I learn.

Will I occasionally come across some news important enough to prompt me to discuss it here?  Maybe.  But, always watching for news and then translating into something my Mom can understand (even though she's pretty smart) has been an increasing source of stress.  So I feel a lot better after giving up on tracking research.

 

More News from the World of Research

I continue to keep an eye out for interesting developments in the world of Alzheimer’s research.  A few have recently popped up for me. So here are some of them: 

1. SHIELD – A new acronym. You may be familiar with the mnemonic for recognizing stroke: FAST – face, arm, speech, time. So now there’s a new one for Alzheimer’s: SHIELD – sleep, head injury prevention, exercise, learning, and diet. Paying attention to these will reduce your risk of developing Alzheimer’s and at least slow it down if you do develop it. This mnemonic was developed by neuroscientist Rudolph Tanzi, co-director of the McCance Center for Brain Health at Harvard-affiliated Massachusetts General Hospital. You can read more here. 

2. Your brain needs sleep. And speaking of sleep, we’ve had a lot to say about it and its relationship to Alzheimer’s disease. Now, there’s new evidence regarding how sleep works to protect the brain. It’s known that human growth hormone, or somatotropin, is released in the body while we sleep. It stimulates growth, cell reproduction, and cell regeneration, notably in the brain. Researchers at the University of California, Berkeley concluded that sleep and growth hormone form a tightly balanced system with feedback loops. Neuroscientist Daniel Silverman is quoted as saying, "Sleep drives growth hormone release, and growth hormone feeds back to regulate wakefulness, and this balance is essential for growth, repair, and metabolic health." You can read more here. 

3. More on sleep and your brain. And still speaking of sleep, a study at the Mayo clinic found that chronic insomnia may be just as influential on the development of dementia as being a carrier of the APOE4 gene. This was found by following 2,750 people over the age of 70 for five and a half years. The study participants took annual cognitive tests and had brain scans. Researchers tracked the development of amyloid plaques and “white-matter hyperintensities.” The white-matter hyperintensities were damage to parts of the brain involved in communication within the brain. One thought is that these two factors might magnify each other. Here’s a link to the published research. You can read a more easily understood article here. 

4. Cocoa and multivitamin supplements may – or may not – delay cognitive decline. New research provides evidence that cocoa and multivitamin supplement consumption may reduce the progression of cognitive decline and help protect against cardiovascular disease. For brain health, the results were more compelling for multivitamins than the cocoa supplements. Called the COcoa Supplement and Multivitamin Outcomes Study (COSMOS), it was conducted at Brigham and Women’s Hospital – an affiliate of Harvard Medical School in Boston – and the Fred Hutchinson Cancer Research Center in Seattle (where my wife was treated for cancer a number of years ago). Wake Forest University also participated. The study involved 12,666 women aged 65 or older and 8,776 men aged 60 or older. They were followed for an average of 3.6 years through the end of 2020. At least with regard to the multivitamins, daily multivitamin slowed cognitive aging by approximately 60%, or the equivalent of 1.8 years over the 3 years of the study.  It was harder to find a positive effect from the cocoa for brain health.  However, the study suggested a 27% reduction in cardiovascular death and greater cardiovascular benefits among those taking the cocoa supplements regularly. Here’s a link to the research. Here’s a link to an article on the study. 

5. Are all ultra-processed foods (UPFs) bad? Perhaps not. While ultra-processed foods (e.g., frozen dinners, chips, soft drinks, and packaged snacks) are clearly inferior nutritionally to fresh fruits and vegetables, applying the same negative label to them all may be a mistake. According to some researchers from the UK, the label UPF is a blunt instrument that excludes some foods that may actually be good for you.  Since UPFS taste good and encourage eating (or overeating), they may be beneficial to older people who tend to lose weight, sometimes dangerously. And whole grain breakfast cereals would qualify as UPFs while being quite nutritious. Here’s an article on this. Here’s a link to the research. (This is all well and good, but I’m sticking with the MIND diet.)

M116 RIP, 1907-2024

Maria Branyas Morera, known to the world of science as Subject M116, died on August 19, 2024 at the age of 117.  Not surprisingly, she has been the subject of considerable interest and investigation.  Of course, everyone wants to live to 117 (don't they?), and so we want to know what her secret was.  The most notable evaluation of her story was published in the journal Cell Reports Medicine,  What were the takeaways?  Well, two were that she stayed away from toxic people, and she ate a lot of yogurt.  Apparently, a lot of yogurt.  (Yogurt is, of course, good for the gut microbiome.  And what's good for the gut is good for the brain.)  The researchers said that they "performed a high-throughput multiomics study of the world’s oldest living person, interrogating her genome, transcriptome, metabolome, proteome, microbiome, and epigenome, comparing the results with larger matched cohorts."  (Take that, you skeptics.) 

Maria was actually born in the United States to Spanish parents, but her family returned to Spain when she was 8, where she grew up and lived out her life.  Today, we think of Spain as a peaceful place, but it would have been racked by civil war, two world wars, the Spanish Flu, and then a terribly repressive government during the first half of her life.  (Remember for whom the bell tolls ... it tolls for thee.  (Apologies to Ernest Hemingway and John Donne.))

Not surprisingly, the findings of the Cell Reports study focused on both genetics and lifestyle.  She allowed doctors to collect samples of her blood, saliva, urine, and stool and these were studied.  These provided insights on aspects of her health, notably the health of her gut microbiome.  

The researchers observed that she had genetics that favored a long life.  Her lifestyle was what you would expect -- she was socially active (but not with toxic people), she didn't smoke, she didn't drink, and she got regular exercise.  (Although I'm not sure how many jumping jacks she was doing at 116.)  Regarding her diet, the researchers pointed out that she ate a lot of yogurt.  They thought that the yogurt reduced inflammation, which helped extend her life.  

In Catalonia, where her family originated and where she lived, the life expectancy for women is 86 years.  So she sure beat that.

One thing that surprised researchers was the very short length of her telomeres.  Telomeres are regions on the ends of chromosomes that shorten as you age.  They protect the chromosomes, but they shorten as you age and may be associated with lifespan.  Some research has gone into the hope that by preventing the telomeres from shortening, the folks that want to live to 117 and beyond can extend their lives.  This finding suggests that is a false hope.

I'm not sure what all of this means for the folks that want to live to 117.  In 2016, I was told I could expect to live to 85, although the way I feel today, I might go beyond that.  That's good enough for me.

A New Relationship Between Diet and Your Genetics

So we know that carrying one or two copies of the APOE4 gene variant is a genetic marker for increased risk of Alzheimer's disease.  We also know that consuming the Mediterranean diet (MedDiet) reduces your risk of developing the disease.  (I have been focusing on the MIND diet, which is a modified MedDiet.)  But is there an interplay between these two factors?  Maybe so.

According to a recently published study in Nature Medicine, it appears that the MedDiet is much more helpful for people carrying one or two copies of the APOE4 gene.  Recall that APOE4 is the variant of the APOE gene most associated with the development of Alzheimer's.  While some carriers never develop the disease, and some non-carriers do, it still elevates your risk.  There are at least 30 different genes that can contribute to your risk, but the APOE4 is the strongest marker.

But what did the researchers do, and what did they find?  Researchers at Brigham and Women’s Hospital, Boston, studied the serum metabolites in thousands of subjects and compared these to their genetic markers and to their disease status.  

But what's a serum metabolite?  These are the chemical compounds found in blood that are the result of the metabolism of various nutrients.  Obviously, the metabolites from a serving of kale will be different than those from a Snickers bar.  And so, they were able not only to determine who was actually following the MedDiet faithfully, but also to see who's disease status was most affected by their diet -- people with the APOE4 gene or those with the other two variants.  And for that matter, carriers of one or two copies.

As it turns out, persons with kale metabolites in their blood experience a greater benefit of resistance to Alzheimer's if they carry the APOE4 gene than if they didn't.  This also goes for the metabolites of other foods in the MedDiet.  Leafy greens containing some antioxidant carotenoids just stand out.  Note that carriers of the other variants still benefit from the MedDiet, but this population benefits the most.

So, a word to the wise.  If 23&Me tells you that you carry one or two copies of the APOE4 gene -- eat your greens!  (And if you don't ... well, eat them anyway.)

Here's an article of the study.  

Today Is World Alzheimer's Day

Today is World Alzheimer's Day.  The Alzheimer's Association describes it: "World Alzheimer's Day, which takes place every Sept. 21, is a global effort to raise awareness and challenge the stigma around Alzheimer's disease and other dementia.  Join the Alzheimer's Association as we recognize the more than 55 million people across the world who are affected by this terrible disease. Whether you fundraise for the cause, share information about Alzheimer's, or talk to a loved one about dementia, you can make a difference."