Walk to End Alzheimer's 2020 now history...

Amy and I participated in the Walk to End Alzheimer's this past Sunday.  It was a very pleasant experience, and I was gratified to have been supported so well by so many of you.  I was rated a "Top Fundraiser" and a "Grand Champion."  Not sure what the criteria for these two badges are, but I'll take it.

Because of the covid, it was not a group walk.  There was an on-line opening ceremony, and then we were to all walk about two miles in our neighborhoods.  Amy and I walked along the river.

Again, thanks to all who supported us in this!  Your contribution will not only help in the search for a cure, but it will also provide direct support to families struggling with the challenges that Alzheimer's disease brings.

Whither Aducanumab?

The rumor I heard two weeks ago was that it will be a few months before we hear anything from the FDA on approving Biogen's application for approval of aducanumab, but I don't know exactly what that means.  Is that when they will begin their work, or is that when we should expect a conclusion?

In any event, we have just learned that they will at least begin their work very soon -- November 6.  This will include, among other things, public hearings.  This is what I learned from this article.

Aducanumab is not a cure for Alzheimer's disease, but, if it lives up to expectations, it is a major breakthrough that can give a measure of relief to many families and to the healthcare and elder care systems. 

You are invited...

This Thursday, October 8, I will be speaking at the Alzheimer's Association Washington State Community Forum about my experience with Alzheimer's disease.  It's a Zoom meeting, so you don't need to be in Seattle, or even Washington State, to participate -- anyone can join.  And it's free.  If you're interested, you can register here.  It's at 2:00 p.m. Pacific Time, 5:00 p.m. Eastern Time, or 11:00 a.m Hawaiian Time.

 

Conference second day and the latest research update

I attended the second day of the conference, Collaborating for a Dementia-Friendly Washington, on Wednesday.  My part was to participate on a panel  of ten thought leaders, focusing on the major takeaways from the conference.  My takeaway was the utility of the toolkit that the Dementia-Friendly America organization has created for communities to use in understanding their situation with respect to livability of their communities for people with dementia.  It is a very rich and valuable resource.

The week before, I attended a webinar with Maria C. Carrillo, Chief Science Officer of the Alzheimer's Association in which she reviewed the current state of affairs in Alzheimer's research.  Here are a few highlights and interesting statements that I noted:   

• We don't know when the FDA will act on Biogen's request for approval of aducanumab, but there is some thought this may happen in March 2021.
• Aducanumab doesn't cure Alzheimer's disease, but it does appear to slow its progress.  What is significant about it is that it is the first medication that actually addresses the disease process.  Earlier medications, such as donepezil, may temporarily improve cognitive function, but they only treat symptoms.
• If aducanumab lives up to it's potential and even somewhat slows the progress of Alzheimer's disease, it could still significantly reduce the load of dementia patients on the healthcare system. 
  
• Thirty percent of dementia cases are mixed dementia, meaning that more than one cause is at work.
• Knowing what mix of causes is at work in a case of dementia will influence the treatment plan.  Therefore, there has been important work on several new types of PET scans that can more clearly distinguish which mechanisms are at work.  For this reason, the Alzheimer's Association is promoting the idea that Medicare should begin covering PET scans.
• As we've discussed previously, very sensitive blood tests for Alzheimer's disease are nearing approval.  This is very significant, because they will make it easier to identify per-clinical cases and thereby accelerate drug trials.  They are currently looking to recruit about 3,000 test subjects.
  
• There are currently 121 drug candidates involved in 136 trials in progress.  43% of these involve re-purposing previously approved drugs.
• As we noted before, there is a correlation between flu shots and reduced incidence of Alzheimer's disease.  No one knows why.  It may simply be that people who get flu shots tend to be people who live a healthier lifestyle.
  
• More work is needed to investigate Alzheimer's disease in non-white populations.  In the U.S., the disease incidence and progression is different among African American and Hispanic populations.  Much of the research to date has focused on Europeans and Americans of European ancestry.
• The current goal is the have a cure for Alzheimer's disease by 2025.
  

Conference First Day

 Today was the first day of our Washington State virtual conference for collaboration on making our communities dementia-friendly.  It runs two days, ending both days at noon.  I spoke this morning and will speak again tomorrow.  According to Zoom, we had a full 200 participating, but they anticipate another 30 or so will view the recording later.

Both days, my participation is as a discussion panelist.  There were four of us on today's panel, and there will be ten on tomorrow's.  Both days I lead off.

Both days, much of what we talk about is our reaction to earlier topical presentations.  Today, we reacted to the keynote speaker, an official with the organization Dementia Friendly America in Washington DC.  My main point was that I am very impressed with the toolkit the organization has developed to aid communities that have discovered they need to improve the habitability of their community for people with dementia.  I'm thinking that I'll likely follow up on that tomorrow, depending on whatever else I see before the panel discussion tomorrow.

Can flashing lights treat Alzheimer's disease?

A couple of weeks ago, my son sent me a podcast about research into using flashing light to reduce beta amyloid in the brains of laboratory mice.   The podcast was from the program Radiolab at WNYC radio in New York.  The research used the familiar model of mice whose genes had been edited to cause the brain to form beta amyloids, similar to what occurs in Alzheimer's disease.  

The researchers drilled a hole in the skulls of mice and inserted a fiber-optic thread down into the hippocampus.  In a way that's not clear to me, they had caused some cells to be light sensitive, and they pulsed light to these cells at a frequency of 40 Hz.  After just one hour, they found that forty to fifty percent of the beta amyloid had been removed!

In the new edition of Beating the Dementia Monster, we discuss the role of microglia cells in the brain in removing trash, including tau tangles and beta amyloid accumulation.  In older brains, the microglia can become less effective, and this allows the tangles and amyloid plaques to accumulate and complicate brain function.  This appears to play a role in the progression of Alzheimer's disease.

The ideas behind the pulsating light is that it re-invigorates one of the rhythms in the brain that, as in a computer, coordinates the activities of different components.  The rhythm in question is called gamma, and it seems to regulate the activity of microglia.  If age has caused the gamma to falter, this method promises to remedy that.  But drilling holes in your head?

The research is being led by Dr. Li-Huei Tsai at MIT's Picower Institute of Learning and Memory.  Dr. Tsai is a remarkable neuroscientist who has contributed substantially to many of the issues we have discussed on this blog.

So how does she propose to stimulate the gamma without invading the brain?  They put the mice into a room where they pulsed light at 40 Hz and got the same result -- a 50% reduction in beta amyloid.

But are the eyes and fiber-optic cables the only pathway from the outside world into the hippocampus?  What about the ears?  Dr. Tsai's team used a 40 Hz audio pulse, and got similar results ... with the mice.

An important question is, does this process result in improved cognition?  At least in mice, some of Dr. Tsai's tests suggest that it can even recover what might have been lost memories.

Will this work on humans?  In research, the record of applying the findings from mouse models to humans is pretty dismal.  Mice aren't people, and that's not really Alzheimer's disease in the mice.

Most of the work with mice was conducted in 2016, but clinical trials with humans began in 2019.  These are one year trials in which people with early stage Alzheimer's disease are subject to an hour a day of combined visual and auditory stimulation at the magic 40 Hz.  Test subjects are evaluated periodically, both for cognition and by MRI.  What are the results so far?  Dr. Tsai is pretty tight lipped, but she seems to be optimistic.

After the research was initially published, a few entrepreneurs developed devices to deliver 40 Hz light to consumers, and these are available at places like Amazon.  The research to support these is still ongoing, but, on the surface, the consumer items seem benign.  I would not advise using one, because they are unproven, and there are warnings that they may cause serious problems, especially for people with epilepsy.

Can contaminated surgical instruments spread Alzheimer's disease?

 Now there's a scary thought!  

A few years ago, some researchers found reasons to believe that amyloid seeds could be carried from one neurosurgery patient to another via surgical instruments.  This implies that contaminated instruments could transmit Alzheimer's disease between patients undergoing neurosurgery.  This in turn led to some alarming headlines.

Now, according to a recent white paper in the British medical journal The Lancet, this risk may exist, but it requires further study to be understood.  The white paper was the product of a working group gathered to investigate the risk.  It was analyzed in this week's Alzfourm.  

The working group concluded that there was little evidence that amyloid seeds could be transmitted during neurosurgery, but the risk shouldn't be dismissed.  Instead, it warranted a long-term epidemiological study.  It also recommended that surgical instruments used for neurosurgery in children be segregated from those used for adults.

If the seeds are actually transmitted, they would come from surgery involving older adults with evolving presence of beta amyloid in their brains.  Once transmitted to a younger person, the seeds would likely take 20 years to develop into a stage of Alzheimer's disease involving cognitive impairment.  Therefore, transmission from one older adult to another would be of much less consequence than transmission from an older adult to a young person. 

One person commenting on the article noted that there are a lot of serious risks that must be considered before any neurosurgery, and the benefits must outweigh those risks.  He suggested that, in comparison, the risk of developing "cerebral amyloid angiopathy" from contaminated instruments is minimal.  Cerebral amyloid angiopathy is a condition involving the familiar beta amyloid, and it is often, but not always, associated with Alzheimer's disease.  The commenter also suggested that further epidemiological study is warranted.