Can a Transfusion from an Exercising Person Convey Brain Health Benefit?

At least in mice, maybe it does.

On October 19 of last year, we cited an article in the Scientific American blog site regarding, among other things, how aerobic exercise fights Alzheimer's disease and resultant dementia.  One of the points the article made is that we should look for ways to artificially create the same conditions in the brain that exist during physical exercise in people subject to potential or actual Alzheimer's disease.  This would be great for couch potatoes, but more importantly, for people who may be too weak to do the kind of exercise that would help them.

Until now, I've seen no ideas proposed for how this might be done.  Until this morning.  There was an article in this week's issue of ALZForum regarding research with mice showing that transfusions of blood plasma from exercising mice promoted brain cell growth in sedentary mice.  No one has tried it yet, but this suggests that transfusions of blood plasma from exercising humans could retard the initiation and progression of Alzheimer's disease in other humans subject to Alzheimer's disease.  (Of course, even if this works, it would be hard to implement on any kind of scale.)

One thing that surprised me in the article was that they never mentioned the brain-derived neurotrophic factor (BDNF) that is usually credited with improved cognition from aerobic exercise.  Instead, they mentioned that there were other proteins generated during exercise in a variety of organs in the body that encourage the generation of new brain cells.  These go into the blood and end up in the brain.  The article cited rises in the concentration of a protein called clusterin in exercising people with mild cognitive impairment.  Clusterin fights inflammation and otherwise helps cells survive in hostile environments.  (Unfortunately, it can help cancer cells survive chemotherapy.)

The article cited research with exercising humans with memory loss which found increases in clusterin in their blood.  The research did not explore changes in cognition as a consequence of this.  I'm not sure if that would have accomplished much, since I don't know how you would separate the influence of BDNF and other factors as causes of improvement.  There are just so many ways in which physical exercise promotes brain health.  

Spoke on Tuesday

On September 26, I spoke at the annual meeting of the Washington State Association of Activity Professionals.  It was a state-wide meeting, and I'm guessing that 30 people attended my track.  Activity professionals provide therapeutic activity programming for the elderly in adult family homes, long term care facilities, senior centers, as well as in assisted living and retirement communities. 

I felt that I was graciously received, and they allowed me to video my talk.  I posted it on the Dementia Monster YouTube channel, and you can see the video here.  (Actually, it should be available after 9:00 a.m. on September 27.  It's uploading as I write this.)

Speaking on Tuesday

Tuesday afternoon I will be speaking at the 2019 Annual Education Conference of the Washington State Association of Activity Professionals.  Activity professionals work with seniors in memory care and other senior living facilities.  It's a statewide meeting, but it will be held here in Richland.  I will be speaking about my experience and what in my experience could be useful to them.  I'll be trying to convey what the people they work with are feeling, but hopefully they will also benefit with respect to what they can do to protect their own brain health.

I am open to other opportunities to speak.  

What is the locus coeruleus, and should I care?

Until relatively recently, conventional MRIs have not imaged a structure in the brain stem called the locus coeruleus (LC).  You can see it in this image.  The LC is about 15mm long by 1-3mm, and appears to play an important role in the formation of memories.  So, not surprisingly, atrophy of the LC is being correlated with neurodegenerative diseases and dementia, notably Alzheimer's disease and dementia with Lewy bodies.

This week's issue of ALZForum carried an interesting article discussing what we know about the LC.  It discussed recent developments in imaging techniques and recent investigations, including those finding the LC is one of the first regions of the brain to accumulate the nasty tau proteins that characterize Alzheimer's disease.  It also discussed the results of cognitive tests and MRIs of healthy young people, older people with healthy LC, and older people with atrophied LC.   Who do you think did best and worst in these tests?

What does the LC do?  It generates the the neurotransmitter norepinephrine used in neurological processes.  Neurons in one part of the LC project toward the hippocampus, and another part projects toward the cerebellum and spinal cord.  Through the release of norepinephrine, LC neurons modulate attention, learning, and memory by manipulating synaptic activity. This is important for network plasticity.

So what good is knowing this?  One thing is the prospect of finding another biomarker for Alzheimer's disease and dementia with Lewy bodies.  The hope is that this can further refine our diagnostic ability, which is important in research on neurodegenerative disease.  If you are testing a new drug treatment candidate, you want maximum confidence that you know what disease or diseases is afflicting the test subject and causing their cognitive decline.

Laughter is the best medecine

My friend Paul recently sent me a news article about comedians helping Alzheimer's disease and other dementia patients.  The article recalls the origins of a group named "Laughter on Call," beginning with a female comedian (Dani Klein Modisett) whose mother was institutionalized with Alzheimer's disease.  She hired a comedian to spend eight hours a week with her mother who had become withdrawn.  The improvements this brought to her mother's mood inspired her to start Laughter on Call.  The organization pairs comedians with dementia patients and sometimes does shows at memory care facilities.  They have attracted attention for improving the quality of life for many Alzheimer's sufferers.

Obviously, this won't help everyone.  Earlier this week, I was visiting a friend in a memory care facility, when another man came and sat with us.  He was quiet and had an expressionless face, although he seemed to want human company.  I asked him what his name was, and he replied in a barely audible voice that he didn't know.

I don't know for sure, but I think this latter man would struggle to follow comedy or the story line of a joke.  On the other hand, he might respond to music.  You may have heard of the documentary film, Alive Inside.  Alive Inside was presented at the 2014 Sundance Film Festival and attracted a lot of attention.  The film examined research on the effect of music on Alzheimer's disease patients, focusing on how music may awaken memories.  I don't know what the effect of music is on the disease itself, but the documentary certainly showed that I-pods could improve the quality of life of people with fairly advanced dementia.     

In the News X2 (#2)

In my previous post, I said I was reviewing two recent news articles on Alzheimer's disease and dementia, and this is the second.

I came across a study from University College London regarding a lower incidence of dementia among people who had been socially active.  The study was entitled "Socially active 60-year olds face lower dementia risk."  This article about the study appeared in the StudyFinds blog.  The upshot was that people who were socially active at 60 were significantly less likely to develop dementia in later life.

The study collected data from some previous studies that made observations regarding 10,228 subjects.  The data went back to 1985, evaluating social activity of subjects at ages 50, 60, and 70.  Between 1997 and 2017 they were given annual cognitive tests.  So this was an ambitious, extensive study that collected a lot of data.

For some reason, the key age for optimal effect seems to be 60.  Subjects with an active social life at age 60 showed a 12% reduction in the likelihood of developing dementia in later life.  Subjects who were active at 50 and 70 also showed less likelihood, but the level of improvement wasn't statistically significant.

If you read Beating the Dementia Monster, you know that I met a neurology researcher who believed that maintaining social connectivity was the single most valuable weapon in fighting Alzheimer's disease.  I'm not sure that's true, but it is clear that it ranks near exercise, diet, and sleep in its power.

In the News X2 (#1)

I saw two recent news articles on Alzheimer's disease and dementia research that I found interesting, and I want to discuss them both.  I'll put them in two different posts.

The AP just published an article on the state of Alzheimer's research that echoed what we have been saying here.  The article was entitled "Scientists rethink Alzheimer’s, diversifying the drug search," and it had some interesting photographs of whole and dissected human brains -- if you're into that sort of thing.  The theme was that the search for a silver bullet pharmaceutical intervention appears to have failed, and a drug approach will need to address a variety of causes of memory loss.

The article cheers the success medical science has had in removing amyloid plaques from brains, but then laments that this has not improved cognition or stopped the progress of the disease.  As we have noted previously, autopsies of people who died of Alzheimer's disease very often exhibit evidence of other causes as well, causes such as Lewy bodies and vascular disease.  This is called mixed dementia, and it is more common than has been appreciated.  Therefore, attacking memory loss must simultaneously attack Alzheimer's disease and the other causes of dementia.

The article went on to discuss other areas where our knowledge of the disease is weak.  We know that herpes virus is often found in the brains of people who died from Alzheimer's disease, so the article discusses a possible link to herpes infection.  (We discussed this in June 2018.)  They also discuss the potential role of gum disease as a player in the etiology of AD -- as we did back in February.  These, of course, raises the possibility of a vaccine for Alzheimer's disease.  So you read it here first.

The article discussed the key role of inflammation in the progress of the disease.  It discussed the role of microglia cells, since they are the brain's immune system.  They attack foreign invader in the brain (and they may perceive amyloid as such an invader), and this immune response includes inflammation.  As with other inflammation responses in the body, the inflammation begins by destroying the enemy but then begins to do a lot of collateral damage to the tissue it is trying to protect.

I was disappointed that the article did not mention lifestyle interventions -- the only way that Alzheimer's sufferer's are currently being helped.  The theme of the article was progress with drug interventions (or lack thereof), but lifestyle intervention research has something to say to drug research.  As several articles have pointed out, understanding why lifestyle changes affect the progress of Alzheimer's disease provides a window into how the disease works and what drug interventions might eventually work.  The Scientific American article we reviewed last October suggested that a drug intervention should attempt to recreate in the brain the conditions that exist during physical exercise.

Visiting Friends

In the past two days I've visited two friends in senior living facilities -- I'll call them Bill and Mike.  I have been friends with Bill for more than 25 years, and I've been visiting him regularly since he began living where he is now.  I know Mike as the husband of Amy's friend, and he just moved in to his facility this week.  Mike's facility is quite near our home, so I will be able to visit him regularly.  Bill is quite a bit farther away, but I've been trying to see him most days.

Bill is in his late 90s and shows considerable evidence of lost mental acuity, but he does not have Alzheimer's disease.  He easily recognizes me when I approach him, although I doubt he could recall my name.  Some days for him are better than others, but only rarely does he seem down.  He laughs easily, and he enjoys it when I read the Bible to him.  Aside from how easily he laughs, I can't help noticing how grateful he is about everything, especially about the people who work there and care for him.  But he's always been that way.

I have been trying to make a video of Bill's life, mainly through interviews.  He can remember his early life on the farm and through high school, but things get hazy after that.  He remembers his service in WWII (wounded in combat), but he has lost the detail that he would relate to me ten years ago.  The project is on hold until his wife is able to jog his memory some more.

Bill does struggle, both physically and mentally.  He has been falling a lot lately, often at night, and we're worried that he might hit his head on something.  But he's usually alert and coherent.  When someone falls in the facility, the first thing the workers do to assess head injury is ask who the president of the United States is.  Bill always seems to know that when I ask him in my own effort to assess where he is at on a particular day.

One day when I visited Bill, he was uncharacteristically down.  He said he was broke and in debt, and he needed a job.  I didn't argue with him, at least not at first.  He then asked me why no one in the facility was wearing their uniforms.  I asked him where he thought we were, and he said on a military base somewhere.  (After leaving the Army, Bill worked as a civilian for the Air Force for many years.)  I asked him what year he thought it was, and he told me, with some uncertainty, 1962.  We spent some time reading the Bible, and I left.

I returned the next day, and he was as well as I'd seen him.  I asked him if he remembered the day before, and he said yes, and he seemed to have a clear recollection of our visit.  He even remembered believing we were on a military base.  He thought I'd chosen the perfect passages in the Bible reading.  His memory is very inconsistent.

His wife visits him every morning, and she usually finds him waiting for her in the lobby.  When I see him in the afternoon he rarely remembers that she was there that morning.

Mike is a different story.  He is in his late 80s, maybe 90, and I don't know him well.  He does display unambiguous evidence of dementia, likely Alzheimer's disease, and his wife was no longer able to care for him at home.  He believed there were three women living in their home -- one who cooked, one who did the laundry, and one who took him to the doctor.

I saw Mike today, two days after he moved into the memory care facility.  I found him in the TV room with two or three other residents.  One woman in a wheelchair was angrily trying to get through a security door to a small courtyard outside.  It kept alarming, until someone from the staff accompanied her outside.  Once outside, she tried to sweep the courtyard from her wheelchair.  Soon she was happy to come in but then wanted help finding food for her mother.  The commotion and the TV made it hard to talk to Mike, but he was happy to see me and had a lot to tell me.

But what Mike had to say didn't make a lot of sense.  He wasn't happy to be there, but he seemed resigned to it.  He complained that if he could only drive a car he would have more freedom.  But he knew he couldn't.  I inferred these things from what he said over a 30 or 40 minute period of time.  He generally spoke in complete sentences that seemed to be meaningful but were unconnected and had no context.  So most of what he said made no sense.  He did not speak in "word salad" as each sentence was a coherent statement, but maybe it was more like a sentence salad.

When I left Mike, i told him that I lived nearby, and I'd be back to see him again sometime soon.

Watch This Space

As the primary focus of the search for an Alzheimer's and dementia treatment moves away from a silver bullet pharmaceutical intervention, there is a lot of work going on to understand the power and limitations of lifestyle interventions.  There are two important studies that I'm watching and, when finished, will tell us a lot.

The first is the MIND diet study, which we discussed before.  The existing evidence is that the MIND diet may be measurably better than either the Mediterranean diet or the DASH diet at improving cognition.  There have been several studies suggesting this, but there is a belief that one more big trial is necessary to convince everyone of it's power.  This highly anticipated study employees 600 subjects and is to run three years.  We expect results in April 2021. 

If you read this blog, you know that I follow the MIND diet, and I am quite enthusiastic about its prospects.  It is particularly suited for Alzheimer's disease, because it addresses both oxidation damage in the brain and neuroinflammation.

The other important study is the US POINTER study, sponsored by the Alzheimer's Association.  The study involves 2,000-2,500 subjects who do not currently show signs of cognitive decline but are at higher risk.  It will examine the influence of lifestyle over a two-year period.  Recruitment began in 2018, and they say we can hope for results in late 2022 or early 2023.

We wrote earlier about the very important Finnish FINGER study, which produced a trove of data relating lifestyle to cognition.  (We noted that it evaluated a diet similar to the Mediterranean diet, but not like the MIND diet.)  So the United States is one of several countries trying to replicate these results, but also putting on our own spin.   For example, Finland has a pretty homogeneous population, where the US and some other countries are more ethnically diverse.  We know that Alzheimer's disease affects different ethnicities differently, so it may be that the effectiveness of lifestyle interventions may vary by ethnicity.  The US study will try to evaluate for this.