Covid Promotes Alzheimer's ... Apparently

The evidence that viruses attacking the nervous system promote Alzheimer's disease is pretty well established.  Think herpes, the virus causing cold sores and shingles.  We've discussed this here before and also in Beating the Dementia Monster.  But what about viruses that don't directly attack the nervous system ... like covid?  There's interesting and troubling news on this front.

In research recently published in Nature Medicine, "Plasma proteomic evidence for increased β-amyloid pathology after SARS-CoV-2 infection," researchers examined a cohort of 1,252 people who had been infected with covid-19.  This was in the UK, and the researchers had access to previous blood test results for Alzheimer's biomarkers for these individuals.  So, for these people, and a for similar cohort of people who had not been infected (a control group), they compared biomarker evidence for Alzheimer's.  Test participants ranged in age from 46 to 80 years of age.  Many of those infected had mild cases, but some had infections serious enough to have been hospitalized.

What did they find?

People who had serious infections, especially serious enough to be hospitalized, showed increased biomarker evidence of Alzheimer's pathology.  They also did less well on cognitive and memory tests.  The specific biomarker they measured was the ratio of two forms of beta amyloid peptide that signal the disease.  The researchers estimated that a serious covid infection was the equivalent of a four-year advance of the disease.

The age of the participants was a factor -- the older, the more vulnerable -- but the presence of high blood pressure was also a factor.

In Beating the Dementia Monster, we discussed the production of a form of beta amyloid that is water soluble and of one that is not.  Both are produced in everyone.  The one that is soluble dissolves innocuously, but the one that is not soluble clumps on to nerve cells and apparently kills them.  Measuring the ratio of these two forms in fluid from a spinal tap or from a blood sample provides strong indication as to whether or not the Alzheimer's pathology is progressing.  So this is what the researchers measured.

Covid-19 is not known to attack nerve cells directly, but it does precipitate "cytokine storms" -- inflammation.  (We discussed this back in 2020.)  Inflammation and oxidation are two fundamental environmental factors in promotion of the disease.  The genetic promoters, notably the APOE4 gene, seem to work by creating an inflammatory environment in the brain.  No one seems to be claiming this with certainty, but it seems likely that any infection that causes inflammation in the brain can promote Alzheimer's.  While it's not yet well understood, there are ways in which inflammation outside the brain can sometimes cross the blood-brain barrier and cause inflammation inside the brain.  So a covid infection in the lungs may precipitate a cytokine storm and cause inflammation in the brain.

The good news is that the varieties of covid now in circulation are not causing the severe disease that covid was causing a few years ago.  Nevertheless, many of us recovered from serious infections a few years ago and may now be more vulnerable to developing Alzheimer's disease.

Cutting the Risk of Young Onset Alzheimer's in Half?

In Beating the Dementia Monster, we wrote that "young onset" or "familial" Alzheimer's disease is caused by three unusual genes, and these almost surely guarantee that you will develop the disease, perhaps as young as in your 30s.  We also wrote in 2022 that the testing of the monoclonal antibody gantenerumab was discontinued by Roche because it appeared to be ineffective against familial or any form of Alzheimer's.  

As with the other monoclonal antibodies (think Kisunla and Leqembi), the treatment is able to remove the plaques of amyloid beta from the brain.  Since development of these plaques is part of how we define the disease, logic said that getting rid of them should slow or even stop development of the disease.  We call this the amyloid hypothesis.  But, in the case of gantenerumab, it didn't.  And so Roche gave up on it.

But hold the presses!  There's a new study finding that gantenerumab can actually cut the incidence of the development of familial Alzheimer's in half!  

So what's different this time?  Well, according to a study published in the April 2025 issue of The Lancet, the key is start early.  Like, decades early.  We know that the disease begins as much as 20 years before the first symptoms, so start the antibody treatment then.

How do you know that it's 20 years before you will develop memory loss and other symptoms of Alzheimer's?  With "old onset" or "sporadic" Alzheimer's, that's a challenge.  But, since familial Alzheimer's is so easily recognized in someone's DNA analysis, and since family member with one of the genes all tend to develop symptoms at about the same age, this becomes a fairly straightforward task. 

The study by researchers largely associated with Washington University, St. Louis involved 73 people with one or more of the genes responsible for familial Alzheimer's.  This genetic makeup all but guaranteed that they would develop Alzheimer’s disease symptoms in middle age.  For a subgroup of 22 participants who had no cognitive problems at the start of the trial and who received the drug the longest (an average of eight years) the treatment lowered the risk of developing symptoms from essentially 100% to about 50%.  Pretty amazing.

A couple of things though.  This was over an eight-year period.  If they continue the treatments, we still don't know if any of the participants will eventually develop memory loss or other symptoms of the disease.  Also, monoclonal antibody treatments can lead to micro-hemorrhaging in the brain, and two study participants had to be removed because of this.  So part of the treatment is administration of regular MRIs to watch for the development of brain abnormalities.  And because work with gantenerumab had been discontinued, the study treatment was shifted from gantenerumab to Leqembi.  Leqembi appeared on the scene late in the study, but has been shown to produce better results than gantenerumab.

So it may be that this discovery will only have value for people likely to develop familial Alzheimer's.  We can't accurately predict those who will develop sporadic Alzheimer's (after age 65), so we won't know if or when to begin treatment.  On the other hand, the ability to treat people who might develop the disease when they still have young families could be a real breakthrough.

I appreciate the comment from an unknown reader of this blog who brought this news to my attention.

After the Test

We have now returned from Seattle, where I had a couple of hours of cognitive tests last Monday.  If you've been following me on this, you know it was for, among other things, a test to validate how well these tests can be done over Zoom.  They tested me over Zoom a few months ago, and now they want to compare the in-person results to see if they're consistent.  At the same time, they'll use the results as part of another study in which they are simply following people diagnosed with some form of cognitive impairment to see how they do over time.  I've been in this study for four years now.

They're not going to disclose the numerical results of the testing to me, but they are able to give me a sense for how I did.  After the results have been analyzed by a neuropsychologist, they'll call and discuss.  It helps that the principal investigator for the test is also my neurologist, so she may be able to be more forthcoming, especially since I'm due for pretty much the same tests with her office this summer.  I asked that they include a qualitative assessment of how I did in comparison to last year.

I learned that the neuropsychologist who will evaluate the results is a person who we discussed in Beating the Dementia Monster; the person who said I was on track to be dead by 75.  I was 66 at the time.  But, in his practice, he focuses on the role of lifestyle in fighting dementia.  At the time, I had just joined the gym and was flipping my lifestyle.  He said that if I would just keep that up, I'll live to 85.  And so it seems, since I'm 75 now.

Overall, I felt pretty well about how I did.  But they did throw a curve that I don't recall facing before.  They gave me a string of numbers and letters, and I had to sort them first numerically, and then alphabetically.  For example, if she says B 3 A 1, I would respond with 1 3 A B.  But how about UY94N7?  It gets really complicated really fast.  I don't know if I got any of them right. 

The trip to Seattle was good.  Our nine-year-old granddaughter was in a community musical production, and we got to see it on closing night.  We couldn't cross the mountains the next day due to snow in the pass, so we stayed another night.  This gave us a chance to take the two girls (the younger being 4) out to dinner at their favorite restaurant.  (They love it, but it's not going to become our favorite...)

Life is good.

Guinea pig ... again

So I have been wanting to write on a couple of subjects, but we're on the move.  Right now, we're in Seattle, and I'm due for a three-hour battery of tests this afternoon.  They want to compare the results of these tests when I took them over Zoom several months ago to what I do today.  Is testing over Zoom just as valid as in person?  If so, it'll save us a lot of travel over the mountains!  Bad in winter.  They're expecting 4 to 8 inches of snow in the pass today and another 4 to 8 inches tonight.  They do a good job of clearing it, so I hope for a smooth trip home tomorrow.

Because it's a research study, they won't tell me the results.  But I've had enough of this testing to know when I've done well or poorly.  And, I'm due for my regular diagnostic cognitive tests this summer. 

One variable is sleep, and I didn't sleep that great last night.  So we'll see how it goes.

Normally, we have the Alzheimer's Association annual Facts and Figures Report by the first week in March.  And it's always fascinating.   But, so far, nothing.  Is that because there just hasn't been that much going on in the world of Alzheimer's research?  Who knows.

There is a new study I want to write about concerning our ability to detect Alzheimer's disease well before the first symptoms appear by examining the retina of the eye.  I've been involved in just such a study, and there's news coming out in this area.  Some consider the retina of the eye to be an extension of the brain, and so, if there are amyloid plaques in the brain there should be some in the retina.  I'll write on this as soon as I can.

Youngest Alzheimer's Patient Ever?

How old do you have to be to get Alzheimer's?  Well, we know that, with young onset (or familial) Alzheimer's, there are cases of people in their 30s, with one case of someone diagnosed as young as 21 years of age.  As we discussed in Beating the Dementia Monster, familial Alzheimer's is caused by any of three specific genes, and if you have one of those genes you'll almost surely develop plaques, tangles, and dementia.  Fortunately, these genes are relatively rare.  There may only be 300 or so families in the world carrying them.  But, as with one family in Columbia, people who develop familial Alzheimer's disease provide a rich basis for study.  People who will develop this form of the disease in the future are easy to identify through genetic testing, and they are more likely to be free of other diseases that afflict older people.  The presence of these other diseases confounds studies of people with Alzheimer's.

But how young can someone be and still develop old onset (or sporadic) Alzheimer's?  This type may or may not have a genetic marker, like the APOE4 gene they test you for at 23andMe, and it's relatively unknown below the age of 65.

Research published in The Journal of Alzheimer's Disease examined the case of a young Chinese man of just 19 years of age who, by all available evidence, suffered from sporadic Alzheimer's disease.  He was still living at the time the research was published, and so there was not yet an autopsy to look for plaques and tangles in his brain.  However, the available biomarkers all ruled out other potential causes of his dementia.  As with me, he had significant atrophy of his hippocampus, and tests of his cerebrospinal fluid were typical for Alzheimer's.  

The young man began to experience problems with memory and cognition when he was 17 and progressed from there.  Neuropsychological tests found him impaired in memory and cognition.  When his case was evaluated, he had no family history of Alzheimer's, and he had no genetic markers for the disease -- the genes for familial Alzheimer's and those that might predict sporadic Alzheimer's.

So is this one of those weird things that just happens?  Some people (wisely) don't think so.  The more we learn about the disease, the more we discover that we don't know.  The authors of the research suggested that studying this case, and perhaps looking for others, might provide important new insights on how and why Alzheimer's develops.

Slow News -- for Now

Of late, I've been struggling a bit to find material that I thing everyone here would find interesting.  I haven't heard of any new breakthroughs in Alzheimer's research, and there's nothing much new with me.  (Good news.). And no new scandals.  (Also good news.)

But this will change.  The first week in March is when the Alzheimer's Association normally releases their annual Facts and Figures Report.  This is always loaded with new insights coming from research, as well as revelations that researchers have been sitting on, waiting for the big moment.  So stand by.

When someone has something substantial to announce, they want to do it when it will get the most exposure.  Important conferences are the best place to do that.  And the most important conference in the world of Alzheimer's research is the Alzheimer's Association International Conference.  This year it will be held in Toronto during July.  So expect interesting things to materialize then.

I have been a little distracted making videos for the Dementia Monster YouTube channel.  Click here.  A lot more effort goes into making a video than a blog post, but my first priority is this blog.  For one thing, there are a lot more subscribers to the blog than the YouTube channel.  (So thank you.)

When I get the Facts and Figures Report, you'll be the first to hear what I find interesting in it.

Social Activity Stalls Dementia -- Really

Tool #2 in the Dementia Toolkit is "Maintain or Increase Social Activity."  But is there a scientific basis for assigning importance to social activity?  Absolutely, and the supporting evidence is getting stronger.

In Beating the Dementia Monster we said that I had met an Alzheimer's researcher, a neurologist with a practice of 22 years, who said that in his experience the most powerful lifestyle factor in brain health is social connection.  When I said I'd heard that physical exercise is most important, he said that people who go to the gym with a friend do much better.

I had a friend named John with dementia.  Our wives were friends, and I didn't meet him until he was already in serious decline.  Eventually he moved into a memory care facility near our home, and I would go visit him pretty much daily.  He was a very pleasant person and easy to talk to ... even when he didn't make much sense.  He said he recognized me each day, but I'm not sure he did.  He  certainly didn't remember my name.

Over the time I visited John, I observed others in the same facility, few of whom had frequent visitors.  My very subjective judgement was that I could observe some of them declining, while John did not seem to decline further.

Until covid.  As soon as covid hit, the whole facility was locked down for a very long time.  Residents ate in their rooms and had no other social activity.  After a few months of this, John died.

I'm not a doctor, and I don't know much about how he was treated for his dementia.  But I am sure that he would have lived a lot longer if his social activity hadn't been cut short.

Which brings me to an interesting study published in the journal Alzheimer's and Dementia, the journal of the Alzheimer's Association.  It was entitled, "Late-life social activity and subsequent risk of dementia and mild cognitive impairment."  The researchers found that maintaining social activity delays the onset of dementia by an average of five, precious years.

Here's another article on the subject.

The research was done at Rush University, where the MIND diet was developed.  They studied 1,923 older adults over a period of seven years, measuring their social activity against changes in cognition.   Social activities they measured included going out for meals, attending sporting events, playing bingo, taking day or overnight trips, visiting relatives and friends, attending religious services, and doing volunteer work.  They controlled for age and physical health.

The researchers noted that 5-year delay in the onset of dementia is worth about $500,000 in health care costs. 

One thing they didn't control for was differences in physical activity.  They said it's possible, for example, that people who visit friends and family often may be more likely to get physical exercise.

So I go down the list of social activities they evaluated.  We don't go to sporting events or play bingo, but we certainly go out for meals (maybe too much?), go on plenty of overnight trips to visit family in Seattle and on the East Coast, attend religious services, and do volunteer work.  I'm an elder in our church, and I've been a volunteer at the food bank for eight years.  And the thing I find most rewarding at the food bank is just working alongside and socializing with other men my age.

So how much of my success is due to the gym versus my social activity?  Or, for that matter diet, fasting, managing stress, practicing Spanish, and sleep?  It's all in the multi-domain approach.  If you're serious, you'll do everything you can.  And it all works.