Intermittent fasting and the brain-derived neurotrophic factor

In our toolkit for fighting and even preventing Alzheimer's disease, physical exercise is our most effective weapon.  This has been validated repeatedly by scientific investigation.  But why?  As we explained in Beating the Dementia Monster, sustained physical exercise -- aerobic exercise -- promotes generation of BDNF, the brain-derived neurotrophic factor.  This is a protein secreted by neurons, and it can prompt stem cells in the brain to form new neurons.

But is aerobic exercise the only way to induce brain cells to generate BDNF?  Well, it's probably the best way, but it's not the only way.

If you are a dedicated reader of this blog (thank you), you will recall that I began intermittent fasting in January of 2020.  I was encouraged to do this by an article I read in the New England Journal of Medicine (NEJM) from December 2019.  When I began, I immediately noticed that my arthritis was reduced.  This is attributable to the ability of intermittent fasting to reduce inflammation throughout the body.  Since then, my doctors find that my memory and cognition have been stable, but it's hard to say if the fasting has been responsible for any of that.  I have been applying all of the tools from "The Dementia Toolkit" we describe in Beating the Dementia Monster, and I don't really know the relative power of each tool.  I just know that, taken together, the results have been great.  (The experts will give the most credit to physical exercise.)

Since January 2020, intermittent fasting has become a fixture of my lifestyle, and I have posted on it periodically.  But I was recently encouraged to take another look at why intermittent fasting would be helpful to brain health.  The NEJM article stated that one effect was that fasting increased the production of BDNF, but I wondered why.   So I recently began reading more research reports on investigation of BDNF and brain health.

With respect to BDNF, most commonly noted was that the switch from a glucose metabolism to burning ketone bodies for energy (metabolic switching) placed stress on neurons.  Metabolic switching occurs during intermittent fasting when the body has consumed its supply of glucose and must turn to other sources of energy.  When neurons were stressed, they generated more BDNF.  Sustained exercise also produces stress.  So this seems to be one reason why intermittent fasting helps with brain health.  But is that all?

In Beating the Dementia Monster, we identified both oxidative stress and inflammation as causes for the propagation of Alzheimer's disease and mechanisms by which the disease kills brain cells.  Diet and exercise go a long way in fighting these, but intermittent fasting also goes after both.

So the theory is that intermittent fasting calms both oxidation and inflammation while prompting the formation of new neurons via the production of BDNF.  (BDNF also helps with the repair of damaged neurons.)  Here is another writer's take on this.

How much confidence do we have with these claims?  Much of it is based on experiments done with mice, and we've said before that mice are not people!  Innumerable times promising research done with mice has failed to produce similar results in humans.  So why do we still use mice so often?  Because often the results can only be developed from an autopsy.  Which complicates things.

One thing worth noting is that autopsies of elderly humans find that those who died with dementia had significantly lower levels of BDNF in their brains than those who did not.

One last comment.  There are supplements out there that are reputed to increase BDNF, and maybe they do.  However, I have not found any research that I find compelling that demonstrates that increasing BDNF through any method other than exercise and fasting actually resulted in improved memory and cognition.  

The Walk to End Alzheimer's

This year, I am again participating in the Walk to End Alzheimer's as an organizing committee  member, event photographer, and walker.  If you follow this blog, you know that Alzheimer's research is very important to me, and the things I've learned from it have powered my improvements.  Behind the governments of China and the USA, the Alzheimer's Association is the third biggest funder of Alzheimer's research in the world.  And the Walk is the Alzheimer's Association's biggest source of funds.  So it's important to me.

Last year, I was the third biggest Walk contribution getter in our region.  This was due in part to the generosity of some readers of this blog.  I'm am so grateful for that.

I'm hoping that this year we will be at least as successful in raising funds for all of the work the Alzheimer's Association does.  If you want to support me in this, please visit my Walk page by clicking here. 

Thanks so much for considering making a contribution!

Alzheimer's disease and covid

Throughout the day on Tuesday of this week, I felt a little off.  By evening, I was feeling a little feverish.  My temperature came in at 99, when it's usually about 97.  So many people I know have been coming down with covid, that I wondered if that was what was going on.  About a month ago I became very ill with all the symptoms of covid, but I tested negative.  The doctor said he believed it was strep.  I did recover from that illness and felt well until this week.

Wednesday morning I had a temperature of 100 and was experiencing more "flu-like symptoms."  So I tested for covid again, and this time it came back positive.  I spoke with a friend who had been with me on Sunday, and he said that he was having the same experience. Toward evening, I felt better, and most of the symptoms calmed down by bed time.  I slept unusually well.  In the morning (today) my temperature was normal, and I felt nothing unusual.  But as the day has worn on, the flu-like symptoms have been returning.  Will I continue to worsen, or will the whole thing dissipate in another day or two?  Who knows.

My son points out that the coronavirus has significant neurologic effects, famously loss of taste and smell.  These have not been serious with me so far, but my lunch today tasted differently than in the past.  So maybe those are catching up with me.  But more worrying are reports of "brain fog."  And recently, more attention has focused on hearing loss and balance.  (Remember that hearing loss aggravates social isolation which aggravates Alzheimer's disease.)  Readers of this blog know that balance is at the top of my list of neurologic concerns.  My balance was unusually bad all day Wednesday, but seems to have returned to how it was before the infection.  So far, anyway.

There is a lot of worry about covid-19 and dementia.  We knew early on that the coronavirus caused unusual inflammation in the brain, a condition that could cause and will certainly aggravate Alzheimer's disease.  But recent research finds that the virus has a whole host of ways in which it causes or supports Alzheimer's disease.  This includes lockdowns that force people into social isolation, a major factor in the development of dementia.  In Beating the Dementia Monster, we discussed the likely role of the herpes virus in the development of Alzheimer's disease, and the coronavirus appears to provide a new pathway for the herpes virus in the brain.  But there are other factors.  This article from the journal, Translational Neurodegeneration surveys both the physiological and societal consequences of covid-19 with respect to Alzheimer's disease.

In the end, will my infection have lasting effects on my disease?  Time will tell.

Do I actually have Alzheimer's disease?

When I tell my story, I'm often challenged with this question: Do I really have Alzheimer's disease?  Someone asserted in a comment on the Amazon listing for Beating the Dementia Monster that I couldn't possibly, although the person wasn't a "verified purchaser" and likely hadn't read the book.  I've even gotten the question from medical professionals.  This is a good question because my case is unusual.  

But why is it unusual?  As we explain in Beating the Dementia Monster, my experience is actually consistent with research in which lifestyles were actually changed and the results measured.  This is notable in the highly respected FINGER study.  The FINGER study has invigorated researchers around the world, and there are many efforts underway to replicate and expand on its results.  The US version of this effort is the US POINTER study now underway.

My initial neurological evaluation was in 2015, first in my home town, and then at Harborview Medical Center in Seattle.  Alzheimer's disease is normally diagnosed through a process that may begin with a screening test, like the "mini mental status exam," and interviews with family members who may have been observing the patient over a period of time.  If these indicate a problem, intensive cognitive tests are administered (about 3-4 hours worth), and the process usually ends with a biomarker test.  The biomarker test looks for a physiological connection to changes in memory and cognition.  In my  case, MRI biomarker examination found that my brain was atrophying in a manner consistent with Alzheimer's disease.  (Since 2015, I have now had seven MRIs of my brain.)  While Alzheimer's disease is only diagnosed definitively in the autopsy, the technology for narrowing the cause of a case of dementia has been getting better and better.

MRIs are considered a little less reliable than a PET scan for assessing Alzheimer's disease.  Until recently, the insurance company wouldn't pay for a PET scan because the results wouldn't change the plan of treatment for a given case of cognitive impairment.  While the MRI can measure atrophy of the brain, PET scans can do several other things depending on the type.  Their original value was in determining where in the brain glucose is being metabolized -- and where it's not.  Alzheimer's disease interferes with the metabolism of glucose, and so there are characteristic changes in patterns of glucose metabolism in the disease.  More recently, new PET scans can measure the load of amyloid plaques and tau tangles.  The plaques and tangles are what make Alzheimer's disease Alzheimer's disease.

While I have ups and downs in my memory and cognition, I have been doing really well, all things considered.  But my balance is still terrible, and balance problems interfere with almost anything I want to do.  My balance problems began to intensify in early 2020, and have been getting increasingly worse.  Maybe I should accept this by virtue of now being 72, but I don't recall either of my grandfathers having balance and gait problems like mine when they were my age.  (My Dad died earlier.)  It's a good bet that my balance and gait problems are being caused or aggravated by Alzheimer's disease -- if that's what I have.

To further refine their diagnosis, my neurologists in Seattle decided I needed a PET scan.  So Amy and I drove over to Seattle a couple of weeks ago, and I spent 45 minutes or so inside another machine.  (Before returning home, we also had a chance to see our granddaughters.)  I got the results of the scan a day or so later and then spent more than an hour on the phone with my neurologist.  The radiologist's report said that there was normal metabolism of glucose throughout the brain.  This is not consistent with Alzheimer's disease and brings into question the conclusion about whether Alzheimer's disease caused my cognitive decline.  

But the steep cognitive decline I experienced in 2015 and the atrophy of my brain are consistent with Alzheimer's disease.  And then the improvements I experienced after my lifestyle changes which work on the disease mechanisms are consistent with recent research.  My question to my neurologist was, have the lifestyle changes so disrupted the disease process that glucose metabolism is now normal ... are the changes obscuring the biomarker evidence of Alzheimer's disease to be found in the PET scan?  She wasn't sure.  And I haven't seen any research that would address this. 

But it seems to me to be very logical.  The principal consequence of exercise and intermittent fasting are to promote production of the "brain derived neurotrophic factor" which we said repairs brain cells and prompts stem cells to form new neurons.  Researchers seem to believe that this is the primary way that lifestyle changes attack Alzheimer's disease.  To have experienced the remarkable improvement in memory and cognition that I have, and to have sustained it over these past seven years, suggests to me that the entire disease mechanism must be impeded to some extent by the suite of lifestyle changes.  The disease mechanisms would include the impaired metabolism of glucose.  So, it seems to me that I shouldn't be surprised to see normal metabolism of glucose in my PET scan, even in the face of Alzheimer's disease.

The PET scan also showed that the metabolism of glucose was less in my cerebellum than other parts of my brain.  The cerebellum has a lot to do with balance and gait.  The metabolism wasn't much less, but it still suggested to me that the problem with my balance is centered there.  But I'm not a neurologist or a radiologist, and my neurologist didn't go there with that observation.  She has some other ideas she wants to pursue.  We'll see how these turn out.    

I've been missing for a couple of weeks.  It took several days for the trip to Seattle for the PET scan, including time to visit with our children.  After that we spent almost a week in California to attend the wedding of my nephew and to see Big Sur.  It was a great trip.  As it turns out, there was no big news in Alzheimer's research during that time, so I don't think our readers missed too much.