Thursday, June 5, 2025

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.

Wednesday, June 4, 2025

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.

Saturday, May 24, 2025

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?

Monday, May 19, 2025

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.

Saturday, May 17, 2025

Updating the Book

In 2020, when we published the second edition in paperback of Beating the Dementia Monster, I knew we had just captured a moment in time. It was a moment in the progress … or regress … of my own disease. It was also a moment in time with respect to research on Alzheimer’s disease. In the book, we pointed people to this blog as a resource regarding what would subsequently transpire with me and with research on Alzheimer’s. I think I’ve done a reasonable job in both areas. 

However, we recently published the audiobook, and I listened to it. I actually kind of cringed a bit. Not because there was anything wrong with the book for 2020, but that so much had changed since those days. We’ve now sold over 13,000 copies of the book, and people continue to buy it. But it’s badly out of date, and I don’t really have the time or energy to produce a third edition. While I’m pleased with how much distribution Google gives us on this blog, all of those 13,000 readers aren’t getting the latest news. Especially since there have been some recent newcomers to the blog, I thought I’d summarize the things I heard in the audiobook that should be clarified. 

First and foremost, at least with respect to Alzheimer’s disease, I continue to do well. My wife and I get to the gym pretty much every day, and we make a serious effort to stick with the MIND diet. They say they want to test me every three years at the University of Washington’s Harborview Medical Center, and this is the third year. So, if they haven’t forgotten me, I should be tested this summer. We’ll see how that goes. But I’ve been participating in several research projects, and I know my memory and cognition have been just fine. My own assessment is that there’s been some deterioration, but it seems consistent with the experience of friends my own age. So it’s consistent normal aging. 

My balance is terrible, and I’m wondering if I won’t be needing a walker in a year or two. But they attribute that to a separate brain syndrome, cerebellar dysfunction. Cerebellar dysfunction may also be causing my insomnia, and they’re investigating that. But I’m 100% happy with my memory and cognition right now. In the future, will the Alzheimer’s reassert itself, especially if I can’t work out at the gym as I have until now? That’s likely, but there’s no sign of that now. 

At the time we went to press with the paperback in 2020, I was looking forward to the outcomes of several important studies. But then covid happened. It, of course, played havoc with pretty much every study out there. I was interested in what was to be the definitive study of the MIND diet as well as the US POINTER study. The US POINTER study was to replicate the results of the FINGER study we discussed in the book. The FINGER study was closer to a randomized controlled trial rather than the much more common and more easily conducted longitudinal studies. In longitudinal studies, they study populations with respect to, for example, exercise and the incidence of dementia. They often rely on surveys and assume people accurately report what they ate and how much the exercised. In the FINGER study, they had actually changed people’s habits and measured the results. So it was more reliable and produced remarkable results. And so it was to be for the US POINTER study. The US POINTER study was to have produced results by early 2023, but that didn’t happen. I’m sure that’s because of covid. According to the web site, the study is still in progress. 

We also expected results from the “MIND Trial to Prevent Alzheimer’s Disease” in early 2021. That, too, fell victim to covid. When the results were finally published July 2023, they were disappointing. In my opinion, covid so disrupted the study as to cause me to doubt it. Also, I had some issues with their protocol. Other published studies of the MIND diet have produced more encouraging results. 

In our book, we we had a positive sense about the monoclonal antibody treatment code named BAN2401. We said that a phase 3 trial was still required to prove whether it worked and if it was safe. That trial was conducted, and the results were reasonably positive. The drug, subsequently named lecanemab, is now approved and marketed as Leqembi. In use, Leqembi does somewhat slow the progress of Alzheimer’s, but it’s not a cure. Like all of the monoclonal antibodies for Alzheimer’s, it can cause microhemorraging in the brain. Patients taking Leqembi must be monitored with periodic MRIs. 

So these are the things that most struck me when I listened to the audiobook, things that could use updating. I hope this is helpful to people who read the book recently, but could benefit from an update.

Wednesday, May 14, 2025

Welcome to New Subscribers

For some reason, we have seen a recent increase in people subscribing to the blog.  Not that we have a huge number of subscribers, but his is still encouraging and rewarding.  So, to new folks, I say, "Welcome!"  And, if you are new, I encourage you to check out our YouTube channel.  Click here.  I don't turn out as much content as other YouTubers, but I try to put out what I think people will find interesting.

Sunday, May 11, 2025

More Detail on Dr. Ornish's Sudy of Lifestyle Interventioins for Alzheimer's Disease

We have written often about the distinction between longitudinal studies and randomized controlled trials.  To date, the majority of the research on lifestyle and Alzheimer's has been longitudinal studies.  You look at a population and take surveys on what people eat, what exercise they get, etc.  You assume that they are telling you (and themselves) the truth about what they do (and don't) eat, and how much real exercise they get.  Then you see how many of them develop dementia.  Many longitudinal studies produce disappointing results, but my view is that the quality of their data is very poor.

In a randomized controlled trial, you change peoples' lifestyles and measure the results.  Rather than rely on self-reporting in surveys, you either control the actual food they eat or measure the chemicals in their blood to see what they've been eating.  With respect to exercise, you supervise the exercise and measure it.  You measure the results with intense cognitive tests, MRIs, PET scans, and blood tests.  Oh, and then there's the control group - a set of test subjects who don't change their lifestyles, but are subject to the same results measurements.

Obviously, the randomized controlled trials are MUCH more reliable.  However, they are much more difficult -- and costly -- to actually perform. 

Back in July of 2024, we reported that Dr. Dean Ornish was completing a randomized control trial of lifestyle interventions for Alzheimer's disease.  We were heartened that he not only found improvements in memory and cognition tests, but he also found improvements in biomarker evidence, specifically Alzheimer's biomarkers in cerebrospinal fluid.  That's now one of the two gold standard tests for diagnosing Alzheimer's.  Dr. Ornish's study involved 51 patients between the ages of 45 and 90, all of whom had been diagnosed with MCI or early dementia due to Alzheimer's.  But only about half of these received the interventions.  For the intervention group, Dr. Ornish found positive results after 20 weeks.

The other day I came across another article referencing this research ... except the article called it "new."  Thinking it was newer than what we discussed before, I started to develop a new post on the research ... before realizing I'd already posted about it.  Nevertheless, I think it's worth revisiting, since the research is so compelling.  And it's so consistent with my own experience.

What I think is worth revisiting are specifics about the interventions used in the study.  So here they are:

Diet: 

Whole foods, minimally-processed plant-based (vegan) diet, high in complex carbohydrates (predominantly fruits, vegetables, whole grains, legumes, soy products, seeds and nuts) and especially low in harmful fats, sweeteners and refined carbohydrates.  It was approximately 14-18% of calories as total fat, 16-18% protein, and 63-68% mostly complex carbohydrates. Calories were unrestricted. Those with higher caloric needs were given extra portions.  Twenty-one meals/week and snacks plus the daily supplements listed below were provided throughout the 40 weeks of this intervention to each study participant and his or her spouse or study partner.  Twice/week, three meals plus two snacks per day that met the nutritional guidelines as well as the prescribed nutritional supplements were shipped overnight to participants and partners.  Participants were asked to consume only the food and nutritional supplements sent to them and no other foods.

This is similar to the MIND diet, except the MIND diet restricts cheese, stick margarine, and butter.  It also allows some poultry and fish. 

Group Support:

Each patient and their spouse or study partner met three times/week, four hours/session via Zoom: 

- One hour of supervised exercise (aerobic + strength training) 

- One hour of stress management practices (stretching, breathing, meditation, imagery) 

- One hour of a support group lecture on lifestyle 

- Additional optional exercise and stress management classes were provided. 

Supplements 

- Omega-3 fatty acids with Curcumin (1680 mg omega-3 & 800 mg Curcumin, Nordic Naturals ProOmega CRP, 4 capsules/day). 

- Multivitamin and Minerals (Solgar VM-75 without iron, 1 tablet/day).

- Coenzyme Q10 (200 mg, Nordic Naturals, 2 soft gels/day). 

- Vitamin C (1 gram, Solgar, 1 tablet/day).

- Vitamin B12 (500 mcg, Solgar, 1 tablet/day). 

- Magnesium L-Threonate (Mg) (144 mg, Magtein, 2 tablets/day). 

- Hericium erinaceus (Lion’s Mane, Stamets Host Defense, 2 grams/day). 

- Super Bifido Plus Probiotic (Flora, 1 tablet/day).

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 ...