Women are more prone to Alzheimer's. Why?

It's well understood that women are more prone to develop Alzheimer's disease than men.  But, of course, women live longer than men.  So it stands to reason that by simply living longer, women will be more susceptible to any disease of old age.  But the numbers don't add up.  Women develop Alzheimer's in numbers too much greater than men to be simply accounted for by a longer life.  Women are also more likely to develop MS than men, but men are more likely to develop Parkinson's, brain tumors, and epilepsy.  Why is that?

I recently came across this interesting article that addresses possible explanations.  For Alzheimer's, two dynamics appear to be the differences in male and female chromosomes (XX for women and XY for men) and hormonal changes during menopause.

The X and Y chromosomes contain genes for sex differences.  However, while women have two X chromosomes, one of then is mostly silenced.  Mostly.  Those genes not silenced (on the chromosome that men lack) appear to be related to the immune system, brain function, and Alzheimer's disease.

The article discusses the consequences of hormonal changes during menopause, but sheds little light on how they might influence the development of Alzheimer's disease.  However, we did write about this back in 2018, with a link to a possibly more insightful article.  Or maybe not.  Mostly, they acknowledge that there must be a role for sex hormones in the development of Alzheimer's, but it's really not clear how that works.

Guts and Brains ... and More Amazing News

We've written before about the gut-brain axis, that mysterious communications system between the microbes in your gut and your brain.  Somehow, they support each other, and an unhealthy gut can mean an unhealthy brain.  So we do what we can to support a healthy gut.  Which means eating right and avoiding chemicals that kill gut microbes, like artificial sweeteners and animal products that might contain antibiotics.

Neurologists like to say that "what's good for the heart is good for the brain."  We might add to that, "What's good for the gut is good for the brain." 

Therefore, we might want to consume products with probiotic bacteria, like yogurt.  However, these microbes are often destroyed in the digestive process and don't always make it out of your stomach.  So there are supplements that can help with that.  And then there are the benefits of prebiotics, "fermentable soluble food fiber," which help supply the needs of the gut microbes.  A a high fiber diet is good for the gut ... which is good for the brain.

The research on the benefits of probiotics and prebiotics continues, and there's some amazing news.  There was a recent study published in Nature Communications using twins to study the effects of consuming prebiotic supplements on memory and cognition.  The results were pretty remarkable, even over a relatively short period of time.

The supplements were inulin, a dietary fiber in the fructan class, and fructooligosaccharide (FOS), a plant carbohydrate sometimes used as a natural low calorie sweetener.  Looking at a box of Costco nut bars, I see a form of inulin listed as an ingredient.  But asparagus is a great source for both inulin and FOS.  For this study, subjects were given supplements, either with both prebiotics or with a placebo.

The study was conducted by Kings College, London, and it used 36 pairs of twins over the age of 60.  One twin was given a daily prebiotic in a protein powder and the other was given a daily placebo in a protein powder.  After only twelve weeks, there was measurable improvement in cognition.  Using some of the same tests used to diagnose Alzheimer's disease, the prebiotic test subjects showed a significant improvement in a cognitive score compared to subjects who took the placebo.

Moral of the story?  Eat your vegetables, especially the leafy greens in the MIND diet!  And it wouldn't hurt to take inulin and FOS supplements.  They're known to be cheap.

There Is News Worth Sharing, But...

... but I've just been really lazy.  My last post to this blog was June 5.  Now it's a month later.

But I do watch the news on Alzheimer's disease and dementia, and I accumulate topics worth sharing.  Usually, I research each story and then try to break it down in a way that would interest most people.  But now, I've accumulated a significant backlog of topics, and I have no hope of researching them all.  But I will share what's come across my computer screen and try to give a little insight on each.  So here:

1.  Alzheimer's disease could be prevented by antiviral drugs already on market.  These are NRTIs, nucleoside reverse transcriptase inhibitors, that are antivirals approved to treat HIV infection, but scientists from UVA Health at the University of Virginia found that patients taking them were less likely to develop the common form of dementia.  Click here.

2.  New Alzheimer’s drug boosts brain protection, restores memory.  A promising drug candidate, DDL-357, improves memory in Alzheimer’s mouse models by increasing levels of a protective brain protein called clusterin (CLU). CLU helps prevent the buildup of toxic amyloid-beta plaques and tau proteins, both key drivers of Alzheimer’s disease.  Click here.

3.  Do viruses trigger Alzheimer's?  A growing number of researchers think so.  (And so do we.)  Click here.

4. SSRIs restore brain function in Alzheimer’s.  A new study suggests that SSRIs, commonly prescribed antidepressants, may reduce biological markers of Alzheimer’s disease. In a cohort of 191 individuals, AD patients on SSRIs had lower levels of plasma phosphorylated tau-181, a key indicator of disease severity.  Brain scans also showed that SSRIs restored metabolic activity in an early site of tau accumulation and serotonin production. This metabolic recovery was not observed in healthy individuals, suggesting a disease-specific effect.  Click here.

5.  Facial stimulation clears brain waste and boosts aging minds.  Researchers have discovered a safe, non-invasive way to enhance the brain’s waste clearance system by mechanically stimulating lymphatic vessels just beneath the facial skin. This gentle technique significantly improves cerebrospinal fluid (CSF) drainage—a critical function that declines with age and contributes to cognitive disorders like Alzheimer’s.  The team used fluorescent tracers in mice and monkeys to uncover a new drainage pathway connecting facial lymphatics to deep lymph nodes, which remains intact even in older individuals. A handheld device that lightly strokes the skin restored youthful CSF flow in aged animals, opening up exciting potential for wearable treatments that prevent or slow neurological decline.  Click here.

6.  The cause of Alzheimer's might be coming from within your mouth.  We wrote about this in Beating the Dementia Monster, but the case continues to grow.  So floss your teeth!  Click here.

7.  Are rosemary and sage the future of Alzheimer’s treatment?  The same herb that flavors your roast chicken is showing promising results in brain research.  Click here.  And here.

8.  Ketogenic diet raises brain blood flow by 22% and BDNF by 47% in new study.  In Beating the Dementia Monster, we said that BDNF was the key biochemical factor that made the Dementia Toolkit work.  Click here. 

9.  Human brains keep making memory neurons in adulthood.  In further confirmation of what we said in Beating the Dementia Monster, a groundbreaking study shows that the human hippocampus continues producing new neurons well into late adulthood. Researchers identified neural progenitor cells—the precursors to neurons—in adults up to 78 years old, confirming ongoing neurogenesis in the memory center of the brain.  Using advanced sequencing, imaging, and machine learning techniques, they traced how these cells develop and where they reside in the hippocampus. The findings may pave the way for regenerative therapies targeting cognitive and psychiatric disorders.  (Of course, as we wrote, BDNF prompts stem cells in the hippocampus form new neurons.). Click here.

10.  Surprise discovery about sugar in the brain could help fight Alzheimer's. Stores of glucose in the brain could play a much more significant role in the pathological degeneration of neurons than scientists realized, opening the way to new treatments for conditions like Alzheimer's disease. Click here.

11.  Spermidine is great for longevity, hair growth and heart health, says expert.  We discussed spermidine briefly in Beating the Dementia Monster.  Click here. 

Why No Cheese?

When we discuss the distinctions between the MIND diet and the Mediterranean diet, the topic of cheese, stick butter, and stick margarine comes up. They are not allowed in the MIND diet. When I speak about this, I might hear a groan from the audience. But what’s wrong with enjoying these common foods? 

The issue was identified by the late Dr. Martha Clare Morris in the longitudinal studies she and her team conducted that led to the development of the MIND diet. She saw a correlation between consumption of these foods and the development of Alzheimer’s disease. And so they were tagged as bad. So that’s correlation. But what does that tell us about causation? 

When asked about causation, dietitians usually point to the saturated fat content of these products. But I’m not sure we know that’s the case. According to some recent research, the story may have more to do with a negative effect that cheese has on the gut microbiome. In fact, while cheese may kill off some beneficial microbes, other dairy products may benefit the microbiome. Quite a paradox. 

In understanding why this might be relevant to our interest in Alzheimer’s disease, we need to recall the mystery of the gut-brain axis. There is some kind of communication between the gut microbiome and the brain, and the brain is in some ways actually controlled by the gut microbiome. The gut is sometimes called “the second brain.” How does that work? If you find out, please let me know! Nevertheless, we associate a healthy gut microbiome with a healthy brain. Eating fermented foods, like sauerkraut and kimchi, are probiotic and are associated with better brain health, because they replenish important bacteria and archaea which may have died at the hands of antibiotics and artificial sweeteners. And, perhaps, cheese. 

The research in question was published in the journal, Nutrients. It studied a relatively small cohort of older men but led to some interesting conclusions. Essentially, dairy, in general, is probiotic and increased the population of beneficial bacteria and archaea in the gut. So dairy is generally good. But cheese, on the other hand, decreased the population of beneficial microbes. Surprisingly, yogurt seemed to be neutral. Yogurt contains some microbes important to a healthy gut, but they may all get destroyed by the digestive juices in the stomach. Or so some believe. On the other hand, older men don’t eat much yogurt, so this may have been the wrong population to use for studying yogurt. (I guess I’m an exception, since I consume plenty of yogurt – mixed with blueberries, walnuts, and monkfruit sweetener.) 

So I’ll speculate. It may well be that saturated fat in butter and cheese is directly detrimental to the brain, promoting the development of Alzheimer’s disease. But also, it may be that the damage to the gut microbiome caused by cheese increased the incidence of Alzheimer’s significantly enough to influence Dr. Morris’s results. 

The research was conducted at Baylor College and involved 34 older men. They basically counted microbes in material taken from their colon mucous and correlated the counts with dairy consumption. Since the study involved such a small population of older men (who didn’t like yogurt) – you guessed it – more research is necessary.

Here's some more, perhaps simpler reading on this.

The MIND Diet -- Dead and Buried -- or Reborn?

In Beating the Dementia Monster, we looked forward to what was to be the definitive study on the MIND diet. The research project was looking to recruit 600 participants, and it appeared that we could expect to see results in April, 2021. The research was a collaboration of Rush University, T. H. Chan School of Public Health, Brigham and Women’s Hospital, and the National Institute on Aging. I was very hopeful for some solid, scientific support for the validity of the MIND diet.  

And then covid happened.

Covid threw a monkey wrench into a lot of plans, including this one. In fact, if you go to the study’s web site, you’d think the research is still underway. The web site stands frozen in time. But they did finally publish the results in July 2023, and the results were disappointing. Some vegan YouTubers were a bit gleeful about this, primarily (it seems to me) because the diet allowed for consumption of some fish and poultry. 

I wrote before that I was disappointed in the quality of the study, because it was compromised by covid restrictions. In my view, some of the adjustments they made to the research protocol impaired data collection and assurance of the validity of the data. After reading the research, it didn’t appear to me that they really knew what people were actually eating with an appropriate level of accuracy. Some took the research results to indicate that the diet really didn’t work to reduce the risk of Alzheimer’s, at least not any better than the Mediterranean diet. But not me.  

So perhaps I’m vindicated in resisting the negative interpretation of the results. Recent research at the University of Hawaii (my wife’s alma mater) used data drawn from 93,000 US adults, of which 21,000 developed Alzheimer’s. The study found that adherence to the MIND diet by members of the general population resulted in a 9% reduction in Alzheimer’s risk. But those of White, Black, and Latino descent experienced a 13% reduction. However, people who improved their adherence to MIND over 10 years (including those who didn’t follow the diet closely at first) had a 25% lower risk of dementia compared to those whose adherence declined. Data for the study was drawn from the research cohort known as the Multiethnic Cohort Study which began in the 1990s. This study was also an initiative of the University of Hawaii, but its original goal was to study the demographics of cancer.  

Now, the MIND diet had not yet been formulated in the 1990s. So this is obviously a longitudinal study in which they analyzed information regarding a large population and looked for correlations between diet and the development of Alzheimer’s. The late Dr. Martha Clare Morris developed the MIND diet based on similar research that she and her team conducted. She describes her research in her book, Diet for the Mind.  

Noteworthy about this new research is that adherence to the diet had relatively little effect on Americans of Asian and Native Hawaiian descent. Positive results were seen in White, Black, and Latino populations. The researchers speculated that this may be because the ethnic foods of Asian and Native Hawaiian cultures was already somehow protective of the brain. And you’re looking for the difference in outcome between what people normally eat and a specialized diet. But if both diets are protective of the brain, you won’t see anything that suggests the MIND diet improved anything. But … as they always say ... more research is necessary.  

The new research hasn’t been published, but it was to have been presented at NUTRITION 2025, the conference of the American Society for Nutrition, this past Monday, June 2, in Orlando. I presume all went according to plan.

A Couple of New Drug Therapy Possibilities

In recent days, two new possibilities for drug therapies have come to my attention. One is a drug that cures mice of their Alzheimer’s and the other is a re-purposing of a class of drugs for HIV. 

In the case of the HIV drugs, doctors at the University of Virginia found that people on them reduced their risk of Alzheimer’s disease by 10% for every year of treatment. The doctors found this by researching 24 years of insurance data involving 270,000 patients. 

So what’s going on with that? 

The drugs are antivirals called “nucleoside reverse transcriptase inhibitors,” or NRTIs. Inflammation is central to both HIV and Alzheimer’s, and these drugs quiet inflammation in the brain. 

While the NRTIs prevent the HIV virus from replicating, they also prevent the activation of inflammasomes. Inflammasomes are proteins involved in the development of Alzheimer’s. We’ve discussed the role of cytokines in inflammation before, and inflammasomes promote cytokine storms. The researchers said that they weren’t surprised that the drug would affect the development of Alzheimer’s by reducing inflammation, but they were surprised by the strength of the effect. 

Of course, “more research is necessary.” In this case, the study was observational, and such studies don’t provide convincing proof of cause and effect. So the authors of the study say that randomized control trials are still needed. But these drugs have been around for a while, and their behavior is otherwise well known. 

The study was published in the May 2025 issue of Alzheimer’s and Dementia, the Journal of the Alzheimer’s Association. 

The drug that cures mice is a promising drug candidate called DDL-357. It improves memory in Alzheimer’s mice by increasing levels of a protective brain protein. The protein is called clusterin, or CLU. CLU helps prevent the buildup of toxic amyloid plaques and tau proteins with which we are familiar. 

Researchers at UCLA found that, in mice, DDL-357 reduces levels of tau, improves mitochondrial function, and enhances cognitive performance. Cognitive performance was tested by the checking the ability of mice to memorize mazes. 

The research was published in the May 2025 issue of the journal Nature, npj | Drug Discovery, “Discovery of a small molecule secreted clusterin enhancer that improves memory in Alzheimer’s disease mice.” 

Since CLU is a protein, there’s a gene responsible for generating it. And at least one variation of the gene inhibits CLU’s effectiveness in controlling the Alzheimer’s amyloid plaques and tau proteins. Among the genetic risk factors for Alzheimer’s, this gene is the third most significant. DDL-357 compensates for the deficiency in the CLU generated by this gene variant. 

Here’s an article that is easier reading than the research paper. 

One nice thing about DDL-357 is that it can cross the blood-brain barrier relatively easily. Therefore, it can be administered orally. But, as we’ve lamented before, this is for mice. What about people? That work remains to be done. How often do we hear about something that works great with mice, but more research is necessary ... and then we don't hear about more research?

Blood Tests at Last

If you want to receive one of the monoclonal antibody treatments for Alzheimer’s disease, you need a formal diagnosis. A formal diagnosis will certainly begin with neurological tests of your memory and cognition as well as interviews with friends and family that know you. But it should also include biomarker evidence. Currently, the gold standard biomarkers are tests of your cerebrospinal fluid via a spinal tap and a PET scan of your brain. The spinal tap is a bit uncomfortable, and the PET scan is expensive.  

But something else is now here, and it’s much simpler, cheaper, and less invasive.  

Consistent with what we’ve said in the past, it’s one of the new blood tests. These tests are very sensitive and comparatively inexpensive. Some researchers claim they identify Alzheimer’s many years before the first symptoms, and, even without insurance, they may cost only a few hundred dollars.  

But until now, insurance wouldn’t cover them, and they couldn’t be used to justify a prescription for the two prominent monoclonal antibody treatments, Leqembi and Kisunla. Why not? Because, up to now, blood tests have not been approved by the FDA for diagnosing Alzheimer’s.  

But that was then, this is now. As of May 16, 2025, the FDA has approved a blood test for Alzheimer’s diagnosis. It is the The Lumipulse G pTau217/ß-Amyloid 1-42 Plasma Ratio (Lumipulse G) test. The test measures the ratio of specific species of tau protein and beta amyloid in the blood that would be anticipated in someone with Alzheimer’s. Lumipulse G was developed by the Japanese medical research and development company, Fujirebio Diagnostics, Inc. (The word “Lumipulse” is a registered trademark of Fujirebio.) Here’s the FDA’s press release on the topic.  

Readers of this blog know that we’ve been following development of these tests since 2018, and this test isn’t the only one out there. It’s just the first to gain FDA approval. So expect more in the future.  

Readers will also know that I believe these tests will be a blow to the long-term care insurance industry if they’re allowed to be a qualification factor for enrollment in one the insurance programs. If, on the one hand, the insurance company knows that you’re already developing Alzheimer’s, will they insure you? If so, at what price? If you learn that you don’t have Alzheimer’s and are unlikely to develop it in the future, will you still be interested in insurance? If so, how much would you be willing to pay? If some people know that they are developing Alzheimer’s, but this is hidden from the insurance companies, won’t they flood the insurance companies with demands for enrollment? And won’t those who learn they don’t have it decide not to enroll in much larger numbers? This will surly skew the actuarial numbers the insurance companies apply in setting their rates.

So, who knows? If nothing else, the tests will help people better understand how to navigate their personal situations.  

Thanks to my friend Mike in Virginia (a high school classmate) for prompting me to write on this topic.