This Season of Light

This is the darkest time of the year, when the days reach their shortest and the nights their longest.  Nevertheless, it's a time when most of us will turn to light.  The ancient Northern Europeans were not alone in counting the days, and then celebrating the gradual return of sunlight.  Jews around the world recently celebrated Hanukkah, the Festival of Lights, in which they recall how the Menorah, even with only a day's supply of fuel, continued to light the restored temple for eight days.  Christians recall the birth of Jesus Christ, the Light of the World.  Others celebrate the light on the faces of little children when they see what Santa Clause has left for them under the Christmas tree.  (I have yet to meet anyone who actually found coal in their stocking.)  Some African Americans will light seven candles to celebrate the seven days of Kwanzaa and their seven principles.  

This was a tough year, and sometimes it seemed that darkness was gaining the upper hand.  Some of us have lost loved ones to the coronavirus, Alzheimer's disease, or both.  Others are struggling through different stages of these diseases.  But these celebrations focus on hope, because there is hope.  The sun will come up tomorrow, and the days will get longer.  Scientists will continue to explore possibilities for treatments.  Care providers, both family and professionals, will comfort those afflicted by disease.  We shall continue to put one foot in front of the other. 

In this season of light, my family and I send you our best wishes.  Our hope for you is that you will have hope, and that hope will not disappoint you. 

Associating Herpes with Alzheimer's Disease

We have written several times in the past about a correlation between herpes infection and Alzheimer's disease.  Correlation is not causation, and no causal relationship has been found.  Nevertheless, the correlation is intriguing.  

A couple of points, most of which we've made before:

• The implicated version of the virus is the Herpes Simplex Type 1, or HSV1.  It's known for causing cold sores.
• Most people contract the virus at some point in their lives, and it often finds a hiding place in the brain.  
• People carrying the APOE4 gene are most likely to show a correlation between a viral infection and Alzheimer's disease in their autopsies.
• There is interest in the possibility that controlling the herpes virus might control at least some forms of Alzheimer's disease.

So will fighting the herpes virus fight Alzheimer's disease?  According to a nationwide study out of Taiwan, the answer is yes.  This was reported in an April 2018 article in the journal Neurotherapeutics.  The study enrolled 33,448 subjects, 8,362 of whom were newly diagnosed with herpes infections.  The infected subjects were treated with antiherpetic medications.  The study concluded, "The usage of anti-herpetic medications in the treatment of herpes simplex virus infections was associated with a decreased risk of dementia."  The risk of dementia was reduced by a factor of 10.

The correlation with the APOE4 gene variant is significant, because it is a factor in many, but certainly not all cases of Alzheimer's disease.  Therefore, treating or preventing HSV1 infection might influence a substantial portion of Alzheimer's cases, but certainly not all.

Coffee, the superfood!

Back in September, we reviewed one of the myriad of superfood lists, noting it identified coffee as a superfood.  (My sister is skeptical of this list because it included coconut oil, but not olive oil.)  How great is that?  But how did coffee end up on the list, especially with respect to Alzheimer's disease?

Probably this 2002 study from Portugal.  It evaluated the caffeine consumption of 54 patients with probable Alzheimer's disease, matched with a control group of the same number of subjects.  It found "Caffeine intake was associated with a significantly lower risk for AD, independently of other possible confounding variables. These results, if confirmed with future prospective studies, may have a major impact on the prevention of AD." 

According to this article or originating in Inverse, there are other reasons to consider coffee a net plus for health benefits.  It cites:

• Decreased risk of heart disease
• Reduce risk of colorectal cancer
•  Protection of the liver 

One problem for some of us who must limit coffee intake for other reasons: the real benefits don't appear to kick in until four cups per day.  Maybe when I was younger, but no now.  As I got into my early 60s, I cut back when it began to interfere with my sleep.  In the past year I've had to cut back because, according to my urologist, some of the acids were irritating my bladder and causing me to awaken repeatedly throughout the night.  So now I'm down to 1/2 cup (6 oz.) per day.

More on Cortisol, Cognition, and Brain Volume

In my last post, I said stress may not cause Alzheimer's disease, but there is evidence that it aggravates its symptoms.  Causative or not (and it may well contribute to causation), elevated cortisol in urine can predict the onset of Alzheimer's disease about three years before the appearance of symptoms.  This is according to a study published in the journal Neurology in January 2017.

This study was brought to my attention by Carl, a subscriber to this blog.  Carl is a PhD chemist living in California who has been successfully battling MCI due to Alzheimer's disease for several years.  He was a participant in one of the aducanumab trials and has shared a number of insights with me.

The study used participants from the Baltimore Longitudinal Study on Ageing. It involved 1,025 participants who contributed urine samples over an average of 10 and a half years (1 - 31 years).  Ninety-four were diagnosed with Alzheimer's disease during the course of the study.  

Biennially, study participants traveled to their test site and spent 24 hours there.  They collected all urine during the 24 hour period and were subject to a battery of cognitive tests.  This is different from similar studies (including the one in my last post), in that other studies used a single blood or other sample taken in the morning for cortisol measurement.  Presumably, the Baltimore protocol controlled for the influence of stress variation throughout the day.  

I would note that participants were taken out of their normal environments when their samples were taken, and those environments likely contained the sources of their stress.  Also, one peer reviewer noted the difficulty of assigning direct cause and effect, suggesting that more study is needed to more precisely understand the mechanisms at work, as well as the role of other factors.  Other factors included blood pressure, insulin resistance, etc.  The study authors agreed with the comment.

Nevertheless, the researchers believe they found that variation in cortisol levels can predict the onset of Alzheimer's disease. 

Cortisol, Cognition, and Brain Volume

In 2015 when I was first told that I had Alzheimer's disease, my care team advised me to make various lifestyle changes, including reducing stress.  Earlier this year, when my cognitive test scores were less than what we'd hoped for, my neuropsychologist and neurologist advised that I should reduce my commitments -- which I have done.  But why would that be important?

It's widely accepted that cortisol, the hormone that rises most prominently when we experience stress, attacks the hippocampus.  The hippocampus appears often to be the first part of the brain affected by Alzheimer's disease, and there have been efforts to correlate stress with Alzheimer's disease.  While stress may not cause Alzheimer's disease, there is certainly evidence that it aggravates the symptoms.  It likely also interferes with the healing that I've experienced through improved exercise, diet, sleep, and social connection.  It appears to do this by inhibiting neurogenesis -- the generation of new brain cells from stem cells.

Case in point -- a study published in the November 2018 issue of the journal Neurology correlated blood cortisol levels in younger and middle-aged adult Americans of European ancestry with cognitive test scores, brain volume, and other markers.  The study population excluded anyone with evidence of Alzheimer's disease.  The study found that "[h]igher serum cortisol was associated with lower brain volumes and impaired memory in asymptomatic younger to middle-aged adults, with the association being evident particularly in women."  (It did not attempt to correlate stress with the subsequent development of Alzheimer's disease.)  

In 2018, Scientific American carried a report on the study, which you can read here.  It featured an interview with one of the investigators.

The study used about 2,000 participants in the Framingham Heart Study, which has now been in progress since 1948.  To arrive at their conclusions, the investigators measured morning blood cortisol levels and then administered various tests of memory, abstract reasoning, visual perception, attention, and executive function. Test subjects also received brain MRIs to assess an array of physical parameters.  As near as I can tell, this was done one time.

What the investigators did not attempt to explain is why cortisol levels had a much greater impact on women than men.  For example, the brain volume associations occurred almost entirely in women.  Another uncontrolled variable was the nature of the lifestyles of the test subjects.  They were all people with the freedom to devote hours to the test, suggesting that their baseline stress levels may be consistent with each another and relatively low.  The question would then be whether they represented the general population.

Surpising new information from the Univesity of Washington

The Alzheimer's Disease Research Center (ADRC) at the University of Washington is closely associated with UW's Harborview Brain Wellness Center.  This is where I get care for my disease.  ADRC is also associated with the research unit at the Seattle VA hospital where I participated in the insulin trial I described in Beating the Dementia Monster.  I've become acquainted with a number of people in research at both Harborview and at the VA hospital.

Each quarter, ADRC publishes a periodical named Dimensions.  I read this carefully whenever it comes out because it often contains very interesting news and information from an important research center.  In the past, I've posted interesting things here that I've learned from reading Dimensions.

2021 is the 35th anniversary of the ADRC (founded in 1986), and the 35th anniversary issue was a blowout.  You can download the pdf version here.  It was, of course, celebratory, but, after reading it carefully, I also learned several new things.

One thing I learned was how central the ADRC has been in developing our understanding of the genetic component of Alzheimer's disease, especially the "familial," young onset form.  Three genes have been identified as causing familial Alzheimer's disease, and researchers at ADRC were particularly instrumental in identifying the third -- presenilin 2.

Dr. Elaine Peskind was principal investigator for the SNIFF (insulin) study at the Seattle VA site.  (She skillfully took a sample of my spinal fluid, among other things.)  In the article, "Research Mystery for the Ages," she provided research results concluding that men and women are equally at risk for developing Alzheimer's disease.  This refutes the existing dogma we describe in Beating the Dementia Monster that women are more susceptible to Alzheimer's disease than men.  Apparently there has been bias in studies that have relied on volunteers, but the Framingham Heart study (a longitudinal study) and a similar longitudinal study out of Rotterdam have been evaluating much more randomized study populations.  These seem to have found no statistically significant greater risk for women of developing Alzheimer's disease.

The article "Prescriptions for Prevention" reviews many things we already know about dealing with Alzheimer's disease, and it covers the same ground (and then some) that we included in "The Dementia Toolkit" of the second edition of Beating the Dementia Monster.  But one thing that jumped out at me was a conclusion that head injury can't be correlated with Alzheimer's disease.  With Parkinson's disease and some other dementias, yes, but not with Alzheimer's disease.  This is different from what I understood earlier.

What wasn't surprising to readers of this blog was a discussion of the frequent ineffectiveness of dietary supplements.  This was discussed in the article "Vitamin Supplements and Nutrition."  It identified research that correlated various agents in certain foods with reduced incidence of Alzheimer's disease, but when these agents are separated from their food matrix, they lose most of their power to do any good.

Of course, in "Prescriptions for Prevention," much was made of the key dynamic of physical fitness.  They don't call for the level of aerobic exercise that I do, but the article is about prevention, not treatment of an established disease process.

Something I considered but didn't discuss in Beating the Dementia Monster was hearing loss.  There is certainly statistical research correlating hearing loss with Alzheimer's disease, but it didn't make any sense to me.  Until now.  "Prescriptions for Prevention" made a connection between hearing loss and social isolation.  In Beating the Dementia Monster, we do discuss the very important association between social connection and Alzheimer's disease.  The correlation between Alzheimer's disease and hearing loss now make sense to me.

Something else interesting was an interview with Dr. George Martin, MD, Emeritus Professor of Pathology at UW and founding director of the ADRC.  He's still active in research and played a pioneering role in identifying the genetic component of Alzheimer's disease.  But founding director?  How old is that guy, anyway?  93, and still at it.  I presume his picture in the magazine is current, but he looks younger than me!

I found this issue of Dimensions to be very rich in content, and I recommend downloading it and reading it.