Is there room for a novel vaccine for Alzheimer's disease?

At the moment, the biggest focus in treating Alzheimer's disease pharmacologically is by using monoclonal antibodies.  Aduhelm, BAN2041, and any treatment candidate with "mab" in its name (e.g. aducanumab) use antibodies originally derived from elderly humans who had developed and deployed the antibodies against beta amyloid accumulating in plaques in their brains.  The derived antibodies are grown and reproduce in the laboratory, and Alzheimer's patients subsequently receive the laboratory-produced antibodies through monthly or biweekly infusions.  At least in the cases of Aduhelm and BAN2401, these antibodies are effective in removing beta amyloid plaques from the brains of Alzheimer's disease patients.  (We continue to look for better evidence to verify the effectiveness of the treatments in significantly moderating the progress and consequences of the disease.)

But is this the only way to clean the brain of amyloid plaques?  A company called Alzamend Neuro, Inc. thinks not.  They would like the patient to develop their own antibodies via a very unusual vaccination process.

Alzamend has developed a method by which they take some of the patient's own immune cells and teach them in the laboratory to recognize beta amyloid molecules.  The cells are returned to the patient's body, where they prompt the immune system to attack the amyloid plaques.  The treatment is code-named ALZN002.

Is this better than monoclonal antibodies?  Based on tests with mice, the treatment appears to be longer lasting and safer than the "mabs."  The claim that it's safer is based on the fact that ALZN002 is using the patient's own cells and so should avoid rejection.  (I don't know what they predict with respect to the microhemorrhaging that plagues the mabs.)

So where does this project stand?  So far, it has only been tested in mice.  But these tests went remarkably well, both from the standpoint of removing amyloids from mouse brains and a lack of adverse side effects.  The next step is to begin human trials.

In this press release, Alzamend announced that they had applied to the FDA for the first US trial of ALZN002.  Normally, the first step would be a phase I trial involving 20 to 80 people, followed by a phase II trial involving several hundred subjects.  The first purpose of the phase I trial is to assess the safety of the treatment, and, in this case, to establish the appropriate dose.  The phase II trial takes a harder look at whether the treatment works or not and may involve several hundred subjects.  

But Alzamend has applied for a combined phase I/IIa trial.  This is not unusual, but I don't know the details of how the trial will be designed.  Alzamend, of course, is hoping for prompt approval of their application so that they can move ahead with the trial. 

Maybe vitamin supplements help with dementia after all?

Back in December 2019, we wrote about research finding that vitamin supplements not only did not improve health, but they were found to be associated with an increase in all-cause deaths.  This came to my attention in a BBC story about how vitamin supplements might actually be bad for you.  This wasn't really news; it was just one more compilation of negative evidence about vitamin supplements.  Consistent with the Alzheimer's Association research conclusions at the time of publication, we said in Beating the Dementia Monster that no supplement had been shown to reverse, stop, or even slow the progress of Alzheimer's disease.  (Some supplements, such as vitamin B-12, could affect the progress of other dementias.)

Fast-forward to September 2022, and the Alzheimer's Association may be changing their tune -- at least tentatively.

In the September, 2022 edition of Alzheimer's and Dementia; the Journal of the Alzheimer's Association, they published the results of a large clinical trial in the UK that did find a correlation between "cognitive benefits" and the administration of multi-vitamin supplements to mostly elderly white men.  

The study involved 2,260 subjects, and results were controlled for the presence of cardiovascular disease.  As we said in Beating the Dementia Monster, there is a strong correlation between cardiovascular disease and Alzheimer's disease.  I presume they wanted to verify that the improvement with respect to Alzheimer's disease wasn't just a secondary effect from the vitamins helping with cardiovascular disease.

The Alzheimer's Association is so encouraged by the findings of this study, that the Chief Science officer, Maria Carillo, issued a press release to announce it.  While they were very circumspect in the discussion, and they didn't recommend that people just start taking vitamins, it's unusual for the Alzheimer's Association to issue a press release about an isolated study like this one.

What multivitamins?  They used Centrum Silver in the study, which I believe is a fairly popular formulation.

One part of the research was profoundly disappointing to me.  They were also studying the ability of cocoa powder as a supplement to affect the progress of Alzheimer's disease.  One of the highlights of my day is taking my ration of dark chocolate whose anti-oxidant properties I'm told will help with my Alzheimer's disease.  But the research came up empty on any benefit from cocoa.  (But I still have faith.)

You can read more here.

How many steps must you take per day to cut your risk of dementia?

Often, when I call my 93 year old Mom, my sister tells me that she's busy "getting her steps."  Her Fit Bit (or whatever she's using these days) has given her a quota of steps to get in, and it's grading her on how well she's doing.  Usually, she's just walking around the house. 

In China, the government expects you to get in a certain number of steps per day, and they too will grade you on your performance.  With an aging population, dementia is an important consideration of the Chinese government.  This is why China is the second biggest funder of Alzheimer's research in the world.

It has become a feature of popular culture that we should all be getting between 5,000 and 8,000 steps in every day for optimal physical health -- depending on who you ask, and who you're talking about.

But where did these numbers come from, and are they right?

At least from the standpoint of protection from dementia, there is new research published in the journal JAMA Neurology finding that the right number could vary from 3,800 to 9,800 steps per day, if your target is dementia prevention.  Click here for CNN's assessment of the research. 

Why such a broad range?  It depends on how much you want to cut your risk.  People between the ages of 40 and 79 cut their risk by 50% by taking 9,800 steps, while those who took 3,800 steps cut their risk by 25%.  Those who walked "with purpose" (power walked at least 40 steps a minute for 6,315 steps) cut their risk by 57%.  And, according to the research, those who got in 10,000 steps cut their risk the most.

These are actually quite doable for most people, but numbers like 10,000 are kind of scary.  So a proposal is that we talk about 112 steps per minute, 30 minutes per day.  The 112 is less scary, but in the research, it exceeded the benefit of 10,000 steps.

This was actually a pretty remarkable study involving 78,000 tests subjects in the UK between the ages of 40 and 79.  They all wore a wrist accelerometer (a fancy word for a Fit Bit or similar device).  The data was used to identify how many steps people got in and at what pace.  Results were based on how many developed dementia of any kind within seven years.

These results should not surprise us.  As we said in Beating the Dementia Monster, I have been told by very knowledgeable researchers that physical exercise is the single most powerful weapon we have to fight both the onset and progress of Alzheimer's disease.  (This is followed by sleep adequacy, diet, and social connection.)

I have also read and been told by authoritative people that there is no treatment, either available or in the pipeline, that will cure Alzheimer's disease.  The best we can hope for is to combine treatments like Aduhelm or (if approved) lecanemab with each tool of our Dementia Toolkit to perhaps prevent, but significantly slow the progress of the disease. 

The Walk to End Alzheimer's 2022 -- Thanks so much!

We had our local Walk last week, on October 9.  I was a member of the planning committee, but also staff photographer, drone pilot, walker, and walk team leader.  I organized a walking team at the food bank, and we called ourselves The Food Bankers.

My goal was $3,000, but I raised $3,155.  My team's goal was $2,000, but we raised $3,875.

I was the third highest fundraiser for the Walk last year.  This year I was #6, but we raised more money overall this year.

Nearly all of the people who supported me are subscribers to this blog.  Thank you so very much!

How good is that Mediterranean diet anyway?

About three and a half years ago, we posted about a study that found the MIND diet might be good for brain health, but the Mediterranean diet might not be so helpful.  This seemed to deny a number of "longitudinal" studies that correlated the Mediterranean diet with a lower incidence or later onset of dementia.  

In Beating the Dementia Monster, we noted that longitudinal studies that follow a population -- correlating behaviors with the appearance of dementia -- must be carefully controlled for confounding factors.  For example, people who eat a healthy diet are much more likely to get good exercise.  So if a study of diet finds a good outcome, was it due to the diet or the exercise?  Or both?  Or some other uncontrolled factor?  Studies looking for correlation between diet and brain health have produced a range of conflicting results.  Some explain this as evidence of variation in how confounding factors (like exercise) are controlled.

Researchers are all quick to point out that, whether or not the Mediterranean diet helps with dementia, it is still profoundly important in the control of other diseases, such as metabolic syndrome.

A recent 20-year study from Lund University in Sweden, published in the journal Neurology, appeared to find that the Mediterranean diet had little influence on the incidence of dementia.  In reading the material, it appears to me that they were more deliberate in controlling confounding factors compared to other studies.

This article in Medical News Today evaluates the research and recalls the same research we cited in our 2019 post.  The upshot is that the Mediterranean diet may not help with preventing, slowing, or stopping Alzheimer's disease, but there is still plenty of evidence that the MIND diet does.  

But where is The MIND Diet Trial we discussed in Beating the Dementia Monster?  Here's what their web site says.  And according to the NIH's "ClinicalTrials.org," they have no results yet.  They were supposed to have published their results two years ago.  I'm thinking they remain a victim of covid.

There have been several promising studies of the MIND diet, so I'm sticking with it.  But the MIND Diet Trial seems to me to be so well designed that, once they can get their results out, we'll have much better confidence in it.  I'm sure it will fare better than the Mediterranean diet.

More on exercise and brain volume

In Beating the Dementia Monster, we cited research finding that even moderate exercise could increase brain volume.  In one study, researchers found that just working in the garden for a year could produce a measurable increase in brain volume.  My neurologist warned, however, that there is not an established correlation between an increase in brain volume and improved memory & cognition.  I've read several studies regarding increased brain volume, and none of them seemed to look for or find a corresponding change in memory & cognition.

And so, speaking of studies on changes in brain volume, there is a brand new one.  It was "Association Between Accelerometer-Derived Physical Activity Measurements and Brain Structure," published in the September issue of Neurology, the journal of the American Academy of Neurology.  What was new in the study was that it found a remarkable increase in brain volume when someone begins exercising a small amount during the week, but there are diminishing returns when the amount of exercise per week is increased.  (Also novel, they used an instrument called an accelerometer to measure how much exercise each test subject was actually getting.)

The study did not appear to look for a concurrent improvement in memory and cognition, even though it mentions neurodegenerative diseases, like Alzheimer's disease.

These results are not consistent with my experience.  I've had seven MRIs of my brain since my initial diagnosis in 2015, and they showed a steady trend of continuing atrophy.  At the same time, my memory and cognition appeared to improve, at least through 2019.  (My neurology care team says it has been stable since 2019, although they found some improvement in 2021.)

You will recall from Beating the Dementia Monster that I joined the gym in December 2015.   This followed decades of a sedentary lifestyle.

When the radiologists look at an MRI, they measure the volumes of the hippocampus and the ventricles (these have been trending toward atrophy), but they also norm them with respect to other men my age.  So while the volumes have been going the wrong way in absolute terms, the normed value of my hippocampus volume has gone from < 1 percentile in 2017 to the 56 percentile in 2020.  That's comforting, but may represent differences in equipment and technique.

So what do we make of the correlation between exercise and memory & cognition?  I still stand by the research we discussed in chapter 8 of Beating the Dementia Monster.  In people who have developed or are known to be developing Alzheimer's disease, memory & cognition begin to improve with an hour or two per week of exercise.  This plateaus at about five and a half hours per week, but memory & cognition begin to decline after about eight hours per week.  In the healthy control group, exercise did not influence memory & cognition.   Consistent with my experience, at about 5 and a half hours per week, memory & cognition were nearly the same as the control group with age-related normal memory loss.

More on Music and Dementia

In the past, we wrote about research regarding the role that music can play in improving the lives of people with dementia.  We particularly highlighted the documentary, Alive Inside, which illustrated the power of music to call those with severe dementia back to our world.  Research in this area continues.

In fact, Dr. Vaishali Phatak, contributor to Beating the Dementia Monster, has been involved in research at the University of Nebraska to study music and dementia.  Her research is through an initiative called "Nebraska Heartbeats."  It's a multidisciplinary collaboration of experts from the fields of music, neuroscience, geriatric psychiatry, dementia care, and music therapy.  

The concept is that the music we knew in our 20s and 30s lives deeply within us, and these memories are less vulnerable to the ravages of neurodegenerative disease.  Memories of music can be used to bring us back to a familiar place, eliciting happy and comforting thoughts.  So the researchers expose persons with dementia to music corresponding to their ages to get a beneficial result.

The researchers tried to launch an in-person pilot in the fall of 2020, but covid restrictions required postponing the effort.  During that time, they noted something we wrote about here -- that the increased isolation of the covid restrictions themselves caused what appear to be premature deaths of some with dementia.  (We wrote about a particular premature covid death of our own here.)  But during that period, the Nebraska Heartbeats team looked for ways to apply music and other therapies to dementia patients living in isolation.  

They published a peer-reviewed  article, "Leveraging Cross-Campus Expertise to Contribute to Dementia Care Through Music," in the journal AMA Journal of Ethics in July of this year.  At this point in time, they're seeking a grant to continue this promising research.  They hope to focus research on the efficacy of music interventions to retrieve memories and benefits to general well being.

Beating the Dementia Monster now in Spanish

Today we published a Spanish language edition of Beating the Dementia Monster on Amazon.  Or Cómo vencer al monstruo de la demencia: Cómo detuve el avance del deterioro cognitivo de la enfermedad neurodegenerativa.  So far, it's just in paperback.  It will take some more work to craft and publish the Kindle version, but that's coming.

I've been working on this for some time, assisted by my friend Alejandro Garcia Ceballos.  Alex has been a great help to me on a number of things, going back to when I needed to learn Spanish in a very big hurry to teach biology in the high school.  (My main tutor was Carlos in Ecuador, but Alex supplemented what Carlos was teaching me.)

It's only been on the market for a couple of hours, so I haven't sold any copies yet.  With the English edition I needed to start a sales campaign, but I have no idea about how to do that for the Spanish market.