Smelling your way to cognitive health...

When I was searching for people with other stories like mine, I encountered a woman who seemed to be delaying the progress of her Alzheimer's disease through a variety of strategies.  These included exercise and diet, but also aroma therapy.  This surprised me.  I had not heard of aroma therapy used as a treatment for dementia, and I wasn't sure how seriously to take her.  But maybe I was wrong to not investigate that further.

One of the Internet algorithms recently decided that I should know more about this.  It brought me to some research finding that smelling menthol may well affect the progress of Alzheimer's disease.  Or at least, it did with our old friends, the mice.

We talked before about the strengths and weaknesses of "mouse models."  Mice can be genetically engineered to have a condition that resembles Alzheimer's disease in humans -- although it's not really the same thing.  It's also easy to train mice and measure changes in their cognitive function.  But they're not people, and their condition is not really Alzheimer's disease.   Some researchers have been led astray by inappropriately drawing conclusions from the results of research with mice.  Nevertheless, we can learn a lot from them -- such as how powerfully physical exercise can moderate progress of the disease.

The research, "Improvement of cognitive function in wild-type and Alzheimer´s disease mouse models by the immunomodulatory properties of menthol inhalation or by depletion of T regulatory cells," was published in the April 2023 issue of the journal Frontiers in Immunology. 

The premise of the research was that there is a complex relationship between the olfactory system and the central nervous system.  And it's not just about being able to detect things in your environment.  According to this article, the olfactory bulb in your nose acts to actually referee and direct different signals, signals associated with different smells, to areas of the brain where the information can be used.  Such as information that a dangerous but smelly animal is about to jump you.

Each molecule floating in the air has a specific shape, and there are electric charges on different points of that shape. Nerves in your nose that are there to detect a specific molecule are shaped like a negative impression of the molecule and with opposite electric charges.  (Remember, opposites attract.)  Since the shape of the molecule fits the nerve ending, and since the charges correspond, the molecule in the air will get stuck to the nerve ending the way a party balloon will stick to the wall.  The nerve will signal the brain, "Hey, I just captured a menthol molecule."  This message causes a reaction in the brain.  So there are nerves designed to detect specific molecules in the air you might encounter.

One thing the researchers noted is that there is often a loss of sense of smell with neurodegenerative diseases like Alzheimer's disease.  They noted a previously recognized association between the nervous system and the immune system.  There is then a complex but, so far, rather mysterious interplay between the olfactory system (for smelling), the nervous system, the immune system, and Alzheimer's disease. They wrote, "The link between impaired [sense of smell] and immune system in neurologic diseases remains to be understood but it opens the door for its potential use in therapies for [neurodegenerative] diseases."

So what did they conclude about what happened with the mice?  They wrote, "Exposure to menthol for 6 months (1 week per month) prevented the cognitive impairment observed in the ... mouse model of Alzheimer's.  ...  These data suggest an association between the immunomodulatory capacity of smells and their impact on the cognitive functions of the animals, highlighting the potential of odors and immune modulators as therapeutic agents for [neurodegenerative] diseases."

Here's another discussion of this research.

This, of course, is very early research on the topic.  But it certainly sounds promising.  Smell menthol for one week per month for six months to stop Alzheimer's disease?  Beats going to the gym.

It's not just me.

When I tell people my story, I'll be met with surprise and, sometimes, disbelief.  "That doesn't happen," I've been told.  When we wrote the second edition of Beating the Dementia Monster, I followed some leads to find others with similar experiences whose stories I could include in my book, but I couldn't find enough compelling cases to make it work.

And sometimes I begin to doubt the diagnosis myself.  I see what's happened to so many others after their diagnoses, and I wonder, why not me too?  So I go back to doctors to hear, "We won't know for sure until the autopsy, but it's almost certainly AD."  And if I remember back to how life was in 2015, it's hard to escape recognizing the hole I was falling in to. 

The problem is that very few people have made the radical lifestyle changes I've made in a manner that can be related to their effect on brain health.  We cited several studies in Beating the Dementia Monster, where this has been done, but I had a hard time finding interesting anecdotes to help my narrative.

But I did recently come across an interesting story that seems to parallel mine.  It's the story of Dr. Rebecca Chopp, who was diagnosed with mild cognitive impairment at about the same age as I was.  Dr. Chopp was chancellor of the University of Denver after being president of Swarthmore College and Colgate University.  Like me, she took on the challenge with respect to life style, and she seems to have experienced similar results.  And, like me, she was motivated to write a book about her experience.  It will be called Still Me; Accepting Alzheimer's disease without losing yourself.  It's due out on Amazon early next year, but should be available for pre-order in November.

Can acupuncture treat dementia?

A lot of people wonder if acupuncture can treat dementia.  That question came to mind when my wife was reading from a web site with interest in Chinese culture.  You likely know that acupuncture is a traditional Chinese medical art involving puncturing specific points in the body with thin needles to achieve objectives in health and well being.  You may also know that there has been a lot of Western interest in it in recent years.

And, it turns out, there have been a number of investigations regarding whether acupuncture can treat cognitive impairment.  What did they find?

Different studies had different results, and the quality of the studies was not high.  These were the findings of an overview of systematic reviews of the topic.  The research was published in the European Journal of Integrative Medicine.  They concluded, "Acupuncture showed potential therapeutic effects for patients with dementia, but the quality of the evidence was not high. Higher-quality randomized controlled trials are warranted to confirm the clinical effects of acupuncture in the treatment of dementia."

Here's another article on the subject from Medical News Today.  They cite a study concluding, "Acupuncture appears to be effective for the mild cognitive impairment that is a precursor for dementia, when used as an alternative or in combination with other treatment,"

Like so many interesting leads in the field of dementia, we seem to need more research before doctors are willing to assert, "Do this, and you'll be cured!"

Alzheimer’s Disease? Dementia? Confusion Still Reigns.

People ask me a lot of questions, but the one I hear most often is, “What’s the difference between Alzheimer’s disease and dementia?” The simple answer to the question is that dementia is a syndrome (not a disease) that can have many causes. Alzheimer’s is a specific disease with a defined but poorly understood etiology that causes 60 to 80% of cases of dementia. But there are other possible causes. 

Seems simple enough, but… 

This distinction has actually been kind of hard to nail down for a long time. Is someone’s dementia caused by Alzheimer’s disease? We don’t know for sure until the autopsy. Until then, all we know with certainty is the person had dementia. So the two terms were used interchangeably for a long time, even among medical professionals. 

As we noted in Beating the Dementia Monster, medical science tried to sort things out in 2011 in a group of interested organizations calling themselves the National Institute on Aging-Alzheimer’s Association workgroups. They tried to standardize the clinical spectrum, describing it as “preclinical Alzheimer’s disease” (AD), “mild cognitive impairment (MCI) due to AD” (or “prodromal AD”), and “dementia due to AD.” They combined these clinical syndromes with biomarkers for amyloid and neurodegeneration that were present at the time. And so, in 2015, on examining my cognitive test performance and MRI biomarker evidence, I was told that I had MCI, most likely due to Alzheimer’s disease. (Earlier in 2015, using pre-2011 terminology, a neurologist recorded that I had “early stage senile dementia, likely of the Alzheimer’s type.”) 

And so, even today, I hear people, even medical professionals, using the terms interchangeably. Some have noted that this confuses people, especially when it’s important to talk to patients and their families about dementia. They further note that something should be done to improve clarity here. 

I recently received a “Special Communication” from JAMA Neurology. (JAMA is Journal of the American Medical Association.) It reported on the work of another work group chartered to bring further clarity to discussion of dementia, along with Alzheimer’s disease and all of the other causes of the cognitive impairment syndromes. The article was entitled, “A New Framework for Dementia Nomenclature.” 

I read the article and saw how an emerging new paradigm could help medical professionals talk to one another … if they all adopt it. But I didn’t think it was so much a “new framework” as an evolution of the old one we described in Beating the Dementia Monster. However, I was uncertain about how it would help doctors talk to their patients, since it seems to be evolving into something even more complicated. 

The framework revolves around this table whose design is intended to yield a disease label. 

You can see that it brings in more considerations, such as the possibility of diseases other than Alzheimer’s disease causing the dementia. So it will likely help the professionals talk to each other (provided they do a better job of adopting it than they did the last one in 2011). 

On the other hand, I’ll be waiting to see if this will actually help patients and their families understand what is overtaking them.  

The more we learn, the more we learn what we don’t know

As we considered in Beating the Dementia Monster, beta amyloid may be a red herring in the search for an actual cure for Alzheimer’s disease.  The amyloid plaques appear as the disease progresses, and removing them seems to improve memory.  But are they a fundamental part of the disease mechanism?  Or are they perhaps something separate, such as a mechanism the body uses to fight a pathogen causing the disease?  Perhaps their effect on memory is simply a secondary phenomenon unrelated to their purpose or origin.  Or maybe they don’t affect memory at all. 

There’s an interesting new study (again, with mice) from the University of New South Wales in Australia that suggests the plaques may not even be implicated in memory loss.  Instead, memory loss results from a breakdown in regulation of the synapses, the tiny spaces between brain cells.  Memories are held in these spaces, and there are special proteins that regulate this activity.  What if there’s a problem with these proteins? 

The research was published in the journal Molecular Neurodegeneration. Recall that RNA plays an important role in the generation of proteins.  RNA editing (which I’d never heard of before) is a process by which the RNA and its resultant proteins are sometimes modified.  This might be a good thing, but it can apparently go wrong.  The research suggested that inappropriately edited RNA generated proteins that did not regulate the synapses correctly.  Our memories live in the synapses, and this apparently destroys them. 

What’s exciting here is that the researchers seem to have found a way to control the errant editing process.  One researcher, Bryce Vissel explained, "RNA editing can be used as a 'molecular switch.'  By flicking the switch in the mice models we use in our research we were able to stop the brain cell connections from breaking down."  This improved memory performance in the mice. 

Can the process they used be adapted to humans?  Will it actually stop the degeneration of brain cells?  More research is required.  (Which is why I support funding research for Alzheimer’s disease.)  

Today's Walk to End Alzheimer's

As it turns out, I met my fundraising goal for this year's Walk to End Alzheimer's.  Thanks so much to all of you who contributed!  The money you pledged will help in a number of ways to defeat this terrible disease.

So my wife Amy and I made the circuit.  (There was an extended route, but I don't think anyone went on that one.). There was a nice turnout, at least as many as last year and probably more.  Click here for a short video where I pan the crowd during the opening ceremony.  Amy is using her phone to take video about half way through.

Here's a picture of me after we had finished.

Yeah, we knew that: dementia risk rises as activity rates fall

That's according to a new study published in the Journal of the American Medical Association (or JAMA).  Other studies we've looked at have told us the same thing, but this one has a very large cohort of subjects - 50,000 people in Great Britain.  

The British maintain a very extensive database of medical information on it's citizens called the UK BioBank.  For this study, researchers looked at data entered for the 50,000 subjects, 60 years of age or older, during the period 2006 to 2010.  Individuals were tracked for an average of seven years.

And the results? Seniors with 12 hours a day of inactivity over a 24 hour period experienced an increased risk for dementia of 63%.  Those who were idle around 15 hours a day had a 320% increase in dementia risk.

This was a longitudinal study, and so we connect cause and effect by inference.  Or perhaps by guessing.  For example, we don't know why people were idle -- perhaps it was a consequence of their existing dementia.  If we knew that, it might change our understanding of the meaning of the results.  This is a weakness in this type of study, although such a large group of subjects is still very informative.

As we've said before, "interventional" or "experimental" studies are more informative.  They actually change something and measure the results rather then simply following a population.  They also use control groups for comparison whose behaviors and other elements were not changed.

An important example of an interventional study is the FINGER study which we discussed previously, both in this blog and in Beating the Dementia Monster.  The study changed behaviors and measured results.  The study conclusions sent shock waves throughout the dementia study community.  

One of concepts behind the scientific method is that others should be able to reproduce your results.  And so there are currently studies all over the world trying to duplicate the FINGER results.  In the United States, we hope the US Pointer study will do this.  The US Pointer study finished recruiting in March of this year and is to last two years.  So it will be late 2025 at the earliest before we see results.  Nevertheless, we have high expectations.  

I expect the US Pointer study to confirm my real-life experience, that changing life style can actually reverse the progress of Alzheimer's disease.  We see this in mice, we think we saw it in the FINGER study, but we want a solid confirmation in a large, well controlled, diverse population.