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.

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.

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.

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).

Some Crazy Stuff about Shingles and Dementia

We've discussed before, both in this blog and in Beating the Dementia Monster, that there seems to be a correlation between people getting their shingle shot and a reduced incidence of developing Alzheimer's disease.  The case for this continues to strengthen, as illustrated in some recent studies in Wales and Australia.  I believe it's likely that my disease stems from my history of three episodes of shingles.

In our book, we noted that some researchers believe that the amyloid plaques we're trying to get rid of are actually part of the body's defense against a variety of microbial pathogens.  The plaques may be trying to encapsulate the pathogens and stop their propagation in the brain.  In our discussion of pathogenic causes of Alzheimer's, we noted researchers have also correlated another pathogen, the bacteria causing gum disease (p. gingivalis), with the advent of Alzheimer's symptoms.  At autopsy, evidence of the presence of the herpes virus and p. gingivalis are usually found in the brains of Alzheimer's victims.

So here's a question.  How does the role of pathogens in the brain correlate with the positive effects of applying The Dementia Toolkit, notably with respect to exercise and diet?  Well, according to one paper, perhaps "environmental factors like stress, diet, sleep, and exercise may influence Alzheimer's risk in part by modulating the innate and adaptive immune responses to [pathogens]."  In other words, the time you spend on the treadmill is regulating the ability of the pathogen to cause damage in your brain.  The paper appeared in the journal, Molecular Psychiatry.  It was entitled, "The viral hypothesis: how herpesviruses may contribute to Alzheimer’s disease."

What's prompting me on this topic is a new study in Australia about a relatively small but consistent correlation between the shingles shot and the advent of dementia.  The study replicated the results of a similar study in Wales.  The Australian study was published in the JAMA Network.  It's a little complicated, but by studying the medical records of more than 101,000 patients with a mean age of about 62 years, there was a 1.8% decrease in the probability of receiving a dementia diagnosis during a 7.4-year period.  That's not a lot, but hopefully most of us will have several more 7.4 year periods after we turn 62.  And the rate of development of the disease increases with age.  So what would that mean for a 7.4-year period beginning at the age of 75?  It might be a lot more than 1.8%

But what may be more important here is the insight this research gives us on the causes and mechanisms of the disease.  As time as gone on, most researchers have migrated away from a simplistic understanding that the disease is fundamentally about the development of amyloid plaques and microtubule tangles.  As a minimum, the amyloid hypothesis has been maturing, and some have abandoned it.

I apologize for being a bit of a slug about posting here.  My wife and I took a trip to a resort area in the Cascades for a few days, and then I was in Seattle for an overnight stay in the hospital while they wired me up to study my sleeping brain.  I'm hoping this will yield a positive outcome for my chronic insomnia.  And, I'll admit it, I have a harder time these days finding the energy to research and write on these topics.  And the YouTube channel is a lot of work.  So I do what I can.

The Lancet Adds Two New Risk Factors for Alzheimer's

The Lancet is one of the premier scientific journals in medicine.  We wrote back in 2022 of the results of the work of the Lancet commission on dementia.  With the unlikelihood that an outright cure for Alzheimer's disease would appear anytime soon, the commission's report highlighted a list of the modifiable lifestyle and other factors that influence the development of the disease.  They will be familiar to anyone who has read Beating the Dementia Monster or who follows this blog.  They were:

- physical inactivity,
- excess alcohol consumption,
- obesity,
- smoking,
- hypertension,
- diabetes,
- depression,
- traumatic brain injury,
- hearing loss,
- few years of education,
- social isolation, and
- air pollution.

The 2022 report included this graphic which showed how the different risk factors map out over someone's lifetime.  Note their conclusion that 60% of the total factors are simply unknown.  Nevertheless, 40% are potentially modifiable - things you can do to affect your susceptibility to the disease.

Then, just last year, the commission released a new study which updated their conclusions.  They noted that, as people live longer, the number of people who live with dementia continues to rise.  But they also noted that, as the age-specific incidence decreases in high-income countries, there is a need to identify and implement prevention approaches.  So much of the report's recommendations focus on changes in governmental policy.

The main takeaways from the new report (after acknowledging the original report) is the addition of two new risk factors: vision loss and high LDL cholesterol (i.e., "bad cholesterol").  But they also said, "The potential for prevention is high and, overall, nearly half of dementias could theoretically be prevented by eliminating these 14 risk factors. These findings provide hope."  They also said, "Although change is difficult and some associations might be only partly causal, our new evidence synthesis shows how individuals can reduce their dementia risk."

I am still waiting for the Alzheimer's Association Facts and Figures Report for 2025.  In the past, this has been a rich resource, even richer than the Lancet's dementia commission reports.  But they still haven't published it.  You can, however, add it to your "wish list" -- which I did.  I presume this means they're still working on it, and we'll see it soon.  In the past, it's been available during the first week in March.  Oh, and, here's a first: I'll need to pay for it now.  Not free anymore.  But I can afford the $7.95.