End of the Insulin Study -- Good News, Bad News

On Tuesday, we went to the VA hospital in Seattle to finish the insulin study.  This required one last round of cognitive tests and a physical.  I was anxious, because I didn't sleep well Monday night.  (I slept well before my April tests, but I bombed the February tests when I didn't get a good nights sleep before those tests.)  But during Tuesday's tests, I could sense that I was doing well.  Afterwards, the study coordinator did a qualitative "eyeball" look at the results in comparison to April, and he said it looked to him like I had done a little better this time than before.  This is consistent with my general sense that I've at least been holding steady for a long time.  This is, of course, consistent with the stability shown in my last MRI.  Did the insulin contribute to how well I did on Tuesday?  Who knows.  But these results were consistent with the trend that was in place before I started on the actual insulin.

The physical didn't go so well.  The PA who conducted the physical called in the senior Doctor and told her I had a heart murmur.  She said it was louder than a Grade 3.  The doctor listened and agreed, indicating that it was not quite grade 4, but loud nonetheless.  They said that I should get in to see a cardiologist promptly -- this week, and I should let them know if I had trouble.

After reviewing events in my life from the past couple of months, they said the murmur was likely due to a heart valve infected following a teeth cleaning.  Since then, I'd awakened at night a couple of times out of breath.  This was likely due to a defective valve causing inefficient pumping of blood.  I also had a sudden, transient event in which my eyes couldn't coordinate.  They said this was likely a TIA related to problems with the heart valve.  The best solution will be antibiotics.  Failing that, I'll need a valve replacement. 

Turned out to be hard to get into see a cardiologist.  Soonest I could get was September 24.  But I was able to get my primary care provider to order an echocardiogram for next Tuesday.  This is good.  I'm sure that my primary care provider can move my situation along as warranted by the test results without the cardiologist.

The researchers were very happy with my performance on the insulin study.  They only had three participants at their site (there were many sites across the country), and the other two had dropped out well before finishing.

When will we know the results of the study?  The team in Seattle doesn't know, but they said they'd tell me when the results are available.  I've learned that if the results aren't very promising, you hear quickly.  If they are promising, they like to wait for a big meeting where they can make a splash with the news.  It's evident to me that they are mostly interested in the results from the first year when the study was placebo-controlled.

They are very interested in engaging me in another, promising study.  I'll wait until after this heart valve business is cleared up before I look into the other one.

What I'm really worried about is the period in here where they don't want me going to the gym.  If they need to replace the valve, I'll be without exercise for a longer time.  Also, anesthesia aggravates Alzheimer's disease, so I don't want that if we can help it.  This could be a double-whammy.    

What's so bad about ApoE4?

The well-known genetic factor in AD is the presence of the ApoeE4 variant of the ApoE gene.  If a genetic testing service tells you that your DNA carries this gene variant, it doesn't mean that you will get AD.  You are, however, at higher risk.  There are other things that can trigger the onset of the disease.  I do not carry the gene, but I have developed AD.

But what does the gene variant do, and why is the ApoE4 gene a factor in development of AD?

There was an interesting article that discussed this in this week's issue of ALZForum.  The article was generally about different proteins and their genes that affect AD, and ApoE was one of them.  It discussed specifically the generation of new neurons in the hippocampus, which is where physical exercise comes in to fight AD.  (Recall from Beating the Dementia Monster that physical exercise promotes the production of "brain-derived neurotropic factor" which promotes the generation of new brain cells.  The generation of new brain cells occurs primarily in the hippocampus.)

At least with respect to the ApoE gene, research found that presence of proteins from the most common gene variant (ApoE3) supports the growth and branching of dendrites in new neurons.  The ApoE4 proteins do not do this and therefore do not support the factors that improve the hippocampus and cognitive performance. 

I thought this was very interesting.       

Party Pooper

In my July 13 post, I wrote about how the glymphatic system removes amyloids and other undesirable substances from the brain during deep sleep.  That's good, except that it appears that there are problems with complete removal of this stuff in older people -- and it aggravates disease.  This is discussed in a recent article in ALZForum that addressed some recent research with mice.

When the cerebrospinal fluid of the glymphatic system collects waste material, it delivers it to the lymph system for complete removal from the central nervous system.  The hand-off occurs with a hidden set of lymphatic vessels in the meninges, the membranes that line the skull and envelope the brain. 

The results of a recent study were discussed in an article in the July 25 issue of Nature, which found that artificially reducing the effectiveness of the hand-off apparently caused greater accumulation of amyloids in the brain and more rapid aging.  Researchers found a likely correlation between reduced effectiveness of the hand-off and reduced cognition.  Some researchers commented that “The finding has implications for normal aging and disorders such as Alzheimer’s disease.”