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."

More Stories in the News

Back on August 25, we posted about stories in the news regarding Alzheimer’s and brain science that had caught my attention. Since then, a few more stories have popped up. Several involved early detection of AD. Here’s what I’ve seen: 

1. While “neural plasticity,” the ability of the brain to constantly break and reconnect pathways in the brain, is an important feature of how a healthy brain functions, this process may go to excess in persons developing Alzheimer’s. Higher flexibility in the networks involved with vision may turn out to be a new biomarker for diagnosing the disease. Here’s an article about it. 

2. Another one bites the dust: A phase 1 study of another anti-amyloid beta antibody developed by a company named Prothena found an unacceptably high rate of brain swelling. The treatment candidate was named PRX012. Brain swelling is a significant side effect for all of the monoclonal antibody treatments, like Aduhelm and Leqembi. Here’s an article about PRX012. 

3. If you successfully completed 10th grade biology, you know that adenosine triphosphate, or ATP, facilitates the transfer of energy in the cell. (Of course you do.) In so doing, the ATP molecule loses a phosphate group that must be restored. It’s the job of another molecule called creatinine to take care of that. For some time, creatinine supplements have been sold to help facilitate physical exercise by supporting the transfer of energy in muscles. But, if you read Beating the Dementia Monster and this blog, you know that the brain uses a LOT of energy itself, and creatinine plays a role there too. New research found that creatinine supplementation in older adults (like me) appears to support healthy brain functioning. So my wife and I take 5-gram creatinine gummies once a day. Here’s an article about it. 

4. A recent study found that the lower concentrations of omega-3 fatty acids in women may help explain why women are more likely to develop Alzheimer’s. This might be remedied by women consuming more foods and supplements with omega-3s. (For example, by eating more salmon.) While we know that beta amyloid plaques and tau tangles characteristically appear in the brains of people with Alzheimer’s, Alois Alzheimer also identified the presence of lipid (fat) droplets in the brain. Failure to move the fats out of the cells may be a part of AD pathology, and it may be we haven’t been paying enough attention to this. And it may be that a poor balance between LDL and HDL cholesterol is inhibiting the proper metabolism of these fats, causing them to accumulate. (Cholesterol has an important role in fat metabolism.) This appears to be more the case with women, and some believe it might explain why women are more likely to develop Alzheimer’s. Part of the equation is the omega-3 fatty acids found in, for example, some fish oils. The recommendation would be to ensure you are consuming enough omega-3 fatty acids, especially if you are a woman. Here’s an article about it. 

5. Is Alzheimer's an autoimmune disease?  We knew that changes in sense of smell can suggest the onset of Alzheimer’s. But why? In Beating the Dementia Monster, we discussed the microglia, cells that form part of the unique immune system in the brain and how they may play a role in Alzheimer’s. Recent research suggests that a loss of control of the immune process causes the microglia to incorrectly identify olfactory nerves and attack them. This would occur in the context of the development of the disease. Hence to correlation between loss of smell and the appearance of the disease. Here’s an article about it. 

6. As we’ve discussed before, there is ample evidence associating vitamin D supplementation with brain health. It’s not just about strong bones. But why? Some recent research correlates adequate vitamin D with the preservation of telomeres, the caps on the ends of chromosomes. They get shorter with age, which makes us more vulnerable to the diseases of old age – like cancer and Alzheimer’s. Vitamin D consumption, whether in the MIND diet or with supplements, protects the telomeres that protect us. Here’s an article about it. 

7. New research reinforces our understanding of the role that problems in the gut might play in influencing the development of Alzheimer’s. The answer is, of course, a high-fiber diet – which is the answer to a lot of problems in the gut. Apparently, immune cells in an unhealthy gut can travel to the periphery of the brain and contribute to the development of the disease. At least in mice. While this finding reinforces our existing observation that a high-fiber diet is essential to brain health, it opens to door to more possibilities in how to understand and treat the disease. Here’s an article about it. 

8. There’s a new three-minute brain wave test that, so far, appears to be very good at diagnosing Alzheimer’s. It’s called the Fastball EEG. Apparently, it’s more reliable than the hours of testing I was subject to when I was diagnosed. Basically, the subject learns a set of eight pictures. Then, he or she is shown a blast of pictures at a rate of three per second. One in five of these is one of the eight pictures the subject learned previously. The EEG then registers the reaction the brain has to what it sees. This is pretty interesting, but, for ease of administration, it’ll come in second to the new blood tests we’ve discussed previously, and it may be no more accurate. Here’s an article about it.  My sense is that this test might be good at recognizing hippocampus damage caused by Alzheimer's, but it doesn't probe the other parts of the brain which may be failing due to other diseases and disorders.

This isn't all.  More next time.

Now We Are Seventy-Six (Apologies to Winnie the Poo.)

Readers of this blog and of Beating the Dementia Monster know that, when I was 66, I was told by an authoritative neuropsychologist and Alzheimer’s researcher that I was on track to be dead by the time I was 75. My subsequent study of the disease found his statement was justified. However, I had also told him that I’d recently done a complete flip of my lifestyle, shifting from one that was quite sedentary to one that was active – joining the gym and paying particular attention to my diet. While I had been working from home without social interaction, I had retired and was now working with other men at the local food bank. This provided more social interaction than I’d had when I was employed. He indicated that, if I kept all of that up, I could expect to live at least to 85. In other words, based on his extensive experience with the disease, I was buying at least 10 years. 

So, about a year ago, I announced here that I had reached that 75, and I wasn’t dead. At least not yet. After all, there are 365 days in a year, and, well, who knows what’ll happen during all those days. I am, however, happy to report that I made it all the way through those 365 days, and I am still not dead. 

But what transpired during those 10 years? Readers will recall that I was in free-fall back in 2015. I had to stop driving and had episodes when I couldn’t recall our zip code or phone numbers of 35 years, even when prompted. After hours of testing at the University of Washington’s Brain Wellness Center I was pronounced “impaired.” In 2017 and 2018, my brain MRIs were for someone in memory care. 

Nevertheless, after about six months of fairly aggressive exercise and work on my diet, I began to see improvement. I may have initially been a bit premature, but I did go back to driving, and I drive quite safely now. Even in Seattle traffic. (But fortunately, we don’t go there very often.) 

I am still followed by the neurologists in Seattle, and I continue to do quite well. My personal assessment is that I continued to improve until 2019, when I seemed hit a plateau. A couple of years ago, I had an essentially normal MRI result, and my memory and cognition are no worse than anyone else I know my age. Within the last hour of preparing this post, I took an online cognitive test for a study at the University of California, San Francisco, and I’m sure that I did just fine. Not perfect, but just fine. About six months ago I took another cognitive test administered for a study at the Brain Wellness Center in Seattle. They weren’t allowed to tell me my exact results, but the results were assessed by the same neuropsychologist who spoke with me back when I was 66. He was at least allowed to tell me that I did just fine. So life is good. 

After we published Beating the Dementia Monster, I met a number of people struggling with memory loss. I usually met them through a spouse who was concerned about them. As I met more and more people who were struggling, I began to appreciate how hard it is for many people to flip their lifestyle the way I did. While I’d lived a very sedentary lifestyle for many years, I wasn’t dealing with any other chronic diseases (yet), and I’d already put considerable effort into getting my weight under control. So I had a head start on getting my physical self in order. I have, however, come to appreciate how hard it can be for many others to replicate my experience, especially if they suffer from chronic diseases. And so, while I do try to encourage people in their 60s and 70s to live well, I’m just as eager to encourage younger people to pay attention to their diet and exercise. 

I do hear from some of you from time to time, and I appreciate that. I’m hoping that there are many who see in me what they can do for themselves and are able to take control of actual or potential memory loss. But it can be hard.

In the News

I haven’t posted much lately, especially with summer travel to the East Coast and North Cascades mountains.  But I have been watching the news on Alzheimer’s disease research.  Here are some things that caught my eye:

1. A study found that having a purpose in life was linked to lower dementia risk.  The study of “over 13,000 adults found that having a strong sense of purpose in life is linked to a reduced risk of dementia. People with a greater purpose were 28% less likely to develop cognitive impairment, even when accounting for genetic risk and other factors.  This was consistent across racial and ethnic groups and modestly delayed the onset of decline by more than a month over eight years. The findings suggest that building purpose through relationships, goals, or meaningful activities may help keep the brain resilient with age.”  Click here.

2. A study found that two supplements can affect levels of gamma-glutamyl transferase (usually referred to as GTP), which is a protein where low levels are seen in Alzheimer’s disease.  (I didn’t know this.)  Some study findings which were published in the journal GeroScience, described how two compounds, nicotinamide (a form of vitamin B3) and epigallocatechin gallate (an antioxidant found in green tea), helped restore guanosine triphosphate, a key molecule that fuels energy production in brain cells. In laboratory experiments on neurons, this treatment not only reversed age-related cellular decline but also enhanced the cells’ ability to clear away amyloid protein clusters, a defining feature of Alzheimer’s.  But these findings seem to have a long way to go before we get to a protocol.  I already take nicotinamide myself, although I don’t drink green tea as often as I should.  Click here.  And here.

3.  We already knew this, but Wendy Suzuki continues to bring attention to the importance of aerobic exercise for brain health.  Click here.

4.  Researchers at St. Jude’s found that a protein, called midkine, blocks amyloid beta from forming harmful clumps linked to Alzheimer’s.  If this checks out, it could lead to breakthrough treatments.  Click here.

5.  Researchers at Harvard found a connection between lithium deficiency in the brain and Alzheimer’s disease.  “The team discovered that loss of lithium in the human brain is among the earliest alterations linked to Alzheimer’s, while in mice, reduced lithium sped up both brain damage and memory decline.”  Click here.

6.  Deficiencies in omega-3 fatty acids may promote Alzheimer’s in women but not in men.  Is this why women are more likely to develop Alzheimer’s than men?  Click here.

7.  Researchers at Rush University (home of the MIND diet) believe they have found out why the MIND diet is effective.  Click here.

8.  In Beating the Dementia Monster, we said that there was a sweet spot for exercise to improve brain health.  But too much is detrimental.  Here’s new research on how it is that too much can be detrimental.  Click here.  Of course, we’re talking a lot of exercise to get over the peak for benefit to get to a downside.

9.  Can AI develop an even better diet for dementia prevention?  The Chinese say they have it.  Click here.  (China is second only to the US government in Alzheimer's research.)