Can the Cabernet and Bree crowd evade Alzheimer's disease?

My friend Jim alerted me to a study published December 15 in the Journal of Alzheimer's Disease finding ways in which diet affects vulnerability to Alzheimer's disease.  The attention-getters were that wine and cheese consumption were correlated with reduced risk of Alzheimer's disease.  The study was entitled "Genetic Factors of Alzheimer’s Disease Modulate How Diet is Associated with Long-Term Cognitive Trajectories: A UK Biobank Study."  (Here's a more accessible discussion.)  It relied on an extensive database of medical histories of 1,787 subjects in the UK.  It was conducted by researchers from Iowa State University. 

Moderate consumption of alcohol, including but not limited to, the form of red wine, has already been correlated with reduced risk of dementia.  However, the idea cheese can be protective flies in the face of other studies, notably the work of Martha Clare Morris, creator of the MIND diet.  (Dr. Morris died of cancer about a year ago.) 

As we discussed in Beating the Dementia Monster, the MIND diet is a hybrid of the Mediterranean diet and the DASH diet, but it excludes cheese, stick margarine, fried foods, sweets, and red meat.  The new study also suggests avoidance of red meat, except that lamb consumed once a week is protective.  (Someone please alert Mary.)  For me, the hardest reach was to avoid cheese.  

Why does research lead to the exclusion of cheese from the MIND diet, while the new study finds that cheese is the most protective food with respect to resisting Alzheimer's disease?  One possible answer occurs to me, and that is differences in how data was sliced and diced in the different research projects.  

From the information I've seen, the researchers in the new study more finely characterized the different research participants with respect to the nature of their diseases.  I say "diseases" because it's increasingly clear that Alzheimer's disease comes in a variety of flavors, based on its genesis.  Some cases are prompted by the presence of the ApoE4 gene variant, while others are prompted by a variant of the gene for the amyloid precursor protein, and some arise from even more genetic variations.  And some variations of the disease may arise entirely from lifestyle problems.  Alzheimer's disease behaves differently in different diverse populations.  These differences seem to correlate with differing manifestations and behaviors of the disease.  The new study appeared to me to control for these differences differently from other studies.

We're hoping for more enlightenment in April.  That's when the results of the (hopefully) definitive study of the MIND diet -- The MIND Diet Trial -- are to be released.  We've been waiting for a couple of years for this, but I'm worried that covid will affect the release.  We'll see, but I'll write about it as soon as results are available.   

Psoriasis and Alzheimer's disease -- are they linked? Does treating psoriasis treat Alzheimer's disease?

Carl, a follower of this blog, wrote to me regarding a study that appeared in Nature; Scientific Reports, in April 2020 -- less than a year ago.  It reported a study from South Korea examining a correlation between psoriasis and Alzheimer's disease.  The study reviewed the cases of about a half million subjects with psoriasis vs. about 2.7 million without psoriasis.  The study noted that both diseases have a genetic component, and research has recently identified genetic overlap between the two.  The study looked for an overlap between expression of the diseases and the genetic overlap.  In other words, if you have psoriasis, are you more likely to get Alzheimer's disease?  

This is a useful question in that psoriasis usually appears at a much younger age than Alzheimer's disease.  Therefore, psoriasis might be a useful predictor of Alzheimer's disease.  At the very least, it might help identify subjects for study of pre-clinical Alzheimer's disease.

And then there's this: Does treating psoriasis also treat Alzheimer's disease?  Good question.

So, does psoriasis increase the risk of developing Alzheimer's disease?  The researchers found "a significantly increased risk of AD in Korean patients with psoriasis compared to a matched control group." After a followup of a little more than three years, 1.87% of subjects without psoriasis developed Alzheimer's disease, while 2.11% of subjects with psoriasis developed Alzheimer's disease.  (These numbers can be misleading, since closer examination is required to consider medications subjects were taking, genetic differences, lifestyle differences, etc.) 

What do psoriasis and Alzheimer's disease have in common?  Both have a strong genetic component for their origins, although other factors (such as lifestyle) play a role.  And, according to the article, the genetic overlap involves genes associated with inflammation.  Inflammation plays an important role in Alzheimer's disease and in some forms of psoriasis.  So, inflammation seems to be the linking factor.  The study noted, "These results indicate that chronic inflammatory conditions in psoriasis may have an important impact on the nervous system and thus in increasing the risk of developing Alzheimer's disease."

As with Alzheimer's disease, there is no cure for psoriasis, but there are treatments.  Some of these target inflammation.  The study reviewed several of the treatments to see if the treatments also affected Alzheimer's disease.  The study found "a significant reduction in the incidence of Alzheimer's disease among patients with psoriasis prescribed systemic medications (acitretin, methotrexate, cyclosporine, and biologic agents) compared to controls without psoriasis."  One drug (acitretin), also appeared to suppress the production of beta amyloid by a separate mechanism.  Unfortunately, these tend to be aggressive medications with substantial side effects.

Recall that in April 2019 we reported on research finding that anti-inflammatory medications, at least non-steroidal anti-inflammatory drugs like naproxen and aspirin, did not help Alzheimer's patients.  Is this an inconsistency?

Another question worth considering:  Could treatments for other inflammatory skin disorders also be effective against Alzheimer's disease? 

As with pretty much every study I read, they closed with "Further studies are needed..."   

Balance and sleep

I'm usually torn between how much to report about myself and how much to keep private.  I want to tell enough about how things are going with me to give others a roadmap of what they might expect if they have my experience with Alzheimer's disease and do what I do.  On the other hand, I tend to be a fairly private person and don't always want details of my life going out.  So, weighing those two factors, I continue sharing what I hope people will find helpful.

In Beating the Dementia Monster, we said that balance problems were the first clue I had that something was wrong.  The neurologist first ruled out a brain tumor (such as my grandfather had), but later diagnosed me with Alzheimer's disease.  He sent me to physical therapy where the therapist said that the balance problems resulted from the death of parts of the brain needed to interpret information from the vestibular system in the ear.  He taught me very effective "habituation exercises" that have helped me to regain balance.  For several years, I would do the exercises every few days to keep my balance tuned up.

Sleep and Alzheimer's disease are interrelated in an unfortunate way.  As we discussed in Beating the Dementia Monster, poor sleep promotes and may even help cause Alzheimer's disease.  But Alzheimer's disease also interferes with normal sleep.  So there is a viscous circle.  Poor sleep promotes Alzheimer's, and Alzheimer's causes poor sleep.

When my trend of cognitive improvement stumbled in April 2019, my neurologist in Seattle attributed this to emerging problems I was having with insomnia.  Over the next year I had some success in improving my sleep, and I believe this largely stabilized my cognition.  As things stand at the moment, I have no recurrence of the troubling things that appeared at the beginning (e.g., couldn't remember important things like phone number and zip code), nor those that appeared in April 2019 (e.g., repeatedly couldn't remember to lock the car door, even when thinking of it while parking).  

I'm comfortable with where I am cognitively right now.  I can manage my own meds, I can manage finances, I can find my car in a big parking lot, etc.  When I test myself with random word recall or mental math, I feel well about the results.  Throughout my experience there have been stumbles, but I continue to follow the elements of the Dementia Toolkit, and I seem to recover OK in the weeks or months following a stumble.

Balance is a different matter.  I noticed some months ago that the habituation exercises seemed less effective.  In the past they could erase transient balance and gait problems, but the exercises were becoming less effective.  I began to fear that I might fall, although I haven't so far.  (I had one strange event about three years ago when I rose from a chair and couldn't move my leg.  After falling, we went to the ER, but they couldn't find anything.  This has not recurred.)

The balance problems have become scary.  To do the wildlife photography that I enjoy, I need to scramble over rocks and climb hills with my equipment.  These have become riskier and more difficult.  I worry that I will have to stop doing these things for the rest of my life.

I saw my primary care provider, who sent me for some new therapy with new habituation exercises.  During intake evaluation, the therapist observed my gait and said that it showed evidence of damage to the basal ganglia.  The basal ganglia are associated with both voluntary motor activity (like walking) and cognition.  

After beginning the new exercises they gave me, I began to wonder if there wasn't another cause for my imbalance.  Perhaps some new meds I'd been given for prostate were the problem?  

To make matters worse, my insomnia got much worse (likely due to both aging and progress of the disease), and the strategies that had been working to give me a better night's sleep stopped working.  Until recently, I would wake up every night at about 3:00 a.m.  But if I got up for about two hours, I could go back to bed, fall asleep, and feel well after arising later.  But more recently, I could not get back to sleep at all, and I was exhausted all day.

So I approached my sleep doctor about finally trying a pharmacological approach to insomnia.  My neurologist in Seattle had suggested trazadone, and my sleep doctor tried this among two other medications.  He tried different medications, because all were causing dizziness and were counterproductive to my work with the physical therapist.

The sleep meds have helped a lot with this, but with two of them, I will still wake up during the night.  At least I can now easily go back to sleep two hours after an episode of insomnia and feel well during the day.  For the moment, I've settled on the medication which causes the least dizziness, and I don't use it the night before I have physical therapy. 

The question remains as to whether I can navigate the sleep and balance issues together.  This is an ongoing project.

Meanwhile, I have now been doing a 20 hour/day intermittent fast with very few interruptions for over a year, but I have no way of determining the effect it has had on cognition.  There are just too many other variables that could be influencing it.  I feel well about the fasting, but the obvious question is what role it might play in balance or insomnia.  By all reports, the fasting should be helpful on both fronts.  Also, if fasting was going to cause a problem, the problem would have shown up long ago.  I plan to continue the fast for the foreseeable future, without knowing how much it's really helping.

In the News

Last month, (January) the Taiwan Food and Drug Administration approved three blood test protocols for Alzheimer's disease developed by the Taiwanese biotech company MagQu Co.  The tests look for beta amyloid in blood samples. 

We've been looking for a viable blood test now for several years, mainly for identifying people with pre-clinical (fancy word: prodromal) Alzheimer's disease to serve as subjects for drug trials.  The tests will support PET scans and cognitive tests to confirm a diagnosis, but will not be sufficient on their own.  However, I'm guessing the blood tests will be sufficient to qualify someone as a drug trial subject. 

I thought we'd have a test in the US by now, but Taiwan seems to be first.

The FDA wants more data, extends its review of aducanumab

We have posted often about the drama surrounding approval of the monoclonal antibody treatment for Alzheimer's disease: aducanumab.  You will recall from Beating the Dementia Monster that I auditioned for the phase 3 trial, but I didn't make the cut.  There were several trials, but they were all terminated when it appeared that the treatment was ineffective.  But then (as we discussed in December 2019), Biogen reevaluated the data and found that, given the right dose, it really was (somewhat) effective.  So they applied to the FDA for approval for clinical use.

So how did the FDA respond?  Well, their advisory committed didn't think that Biogen had made their case.  In November 2020 we discussed the committee's recommendation that Biogen's application be rejected.  But this was advisory only, and the FDA continued to review Biogen's data and their application.  As they continued their review, pressure on the FDA to approve aducanumab mounted.

So where does this stand today?  On January 29, Biogen announced that the FDA had requested additional data and analysis from Biogen in order to complete the review.  Such a request automatically triggers a three-month extension of the deadline for the FDA to complete their review.  The new deadline is June 7, 2021.

What is the nature of the new information, and what does the request mean?  I haven't been able to find out.

Oooops...

A friend wrote to say how impressed he was with my treadmill performance ... that I was going 8 mph!  Pretty impressive!  But what I meant to say was that I begin at 3.3 mph and drop to 3.0 mph when my heart rate hits my target.  Big difference.  (I have since corrected the blog post.)