Why is sleep so important?

In Beating the Dementia Monster, I emphasized the importance of getting a good night's sleep every night.  For younger people, this is a challenge, because so much is going on in their lives.  For us older folks, our physiology seems to get in the way.  Even if we allocate enough time to sleep, getting to sleep and staying asleep is increasingly difficult.

The quality of sleep is important.  REM sleep -- when you dream -- does not appear to provide the benefit of deep sleep.  (REM stand for "rapid eye movement."  Your eyes are moving around when you are in REM sleep, and you are dreaming.)  Analysis of amyloid concentrations in people who have been sleeping indicates that deep sleep does more to control amyloid than REM sleep or no sleep.

Sleep is so important!  Why?

The first question is, why do we sleep in the first place?  For a long time, it was assumed that there was some sort of repair process for the body that occurs during sleep, but no one could find any repair processes going on.  This led to speculation that it was primarily to provide an opportunity for consolidation of mental activity or to keep diurnal animals safely sleeping in hiding places during the night.  Or, for that matter, nocturnal animals would find a safe place to sleep during the day.

These ideas struggled for confirmation, so more recently a better explanation has appeared.  Researchers increasingly believe that a vital function of sleep, at least in higher order animals, is to allow the removal of toxic wastes, including amyloids, from the brain.

As recently as 2015, we discovered a cerebral-spinal fluid circulatory process in the brain which has been named the glymphatic system.  During sleep, especially during deep sleep, the cells in the brain shrink, expanding the space between the cells by as much as 60%.  Cerebral-spinal fluid enters the brain to fill the space.  Expansion and contraction of the cells promotes the movement of the fluid within the brain and its eventual exit from the brain.

As a natural part of cellular metabolism, cells expel waste products, including amyloids.  In other parts of the body, blood and the lymphatic system carry the waste away, but this is not the primary mode of waste removal in the brain.  Instead, these wastes are removed by the movement of the cerebral-spinal fluid of the glymphatic system. 

Amyloids expelled from brain cells accumulate in the space between the cells.  They are then either removed from the brain, or they congregate as plaques on the dendrites of brain cells.  The presence of amyloid plaques is a hallmark of AD, and they play some kind of role in the disease process.  It's  not entirely clear to everyone what that role is, but removing amyloids from the brain has been a focus of developing methods for stopping AD.

The bottom line:  Deep sleep promotes the removal of amyloids from the brain.  This may be a factor in resisting AD.  Failure to sleep well and often enough may be a factor in the development or aggravation of AD.

Here is a National Institute of Health article discussing what we have been learning about the glymphatic system.     

Could it be -- finally?

Will there finally be a drug to at least slow Alzheimer's disease?  This week's ALZ Forums newsletter reported on a drug study that, at the 18-month mark, was showing evidence that it could slow cognitive decline and remove amyloid plaques.  The drug is BAN2401.  It is a monoclonal antibody which selectively binds to certain amyloid cell clusters.  It appears to me that researchers had thought to abandon the trial at the 12-month mark, but persistence to 18 months is paying off.
 
This was a phase 2 trial that tested five dose regimens in people who had mild cognitive impairment due to AD or had mild AD and who had evidence of brain amyloid pathology.  Patients received infusions of a range of doses twice a month.

The trial involved 856 participants which is large for a phase 2 trial.  In fact, it's more like the size of a phase 3 trial.  Recall that, in the past, several drugs showed promise in small population phase 1 trials, but then flamed out with a larger population in phase 2.  While there may be as few as 20 subjects in a phase 1 trial, 865 participants provides much more confidence that results are meaningful!

The drug appears to be safe.  You may recall from Beating the Dementia Monster that a side effect of another monoclonal antibody, aducanumab, was causing micro hemorrhages in the brains of some subjects.  I was happy to be screened out of that one, although there is hope that it may still have a future.

BAN2401 was developed by Stockholm-based BioArctic and was then licensed to Eisai.  Biogen subsequently acquired a stake through a partnership with Eisai.  Eisai/Biogen hope to began a large phase 3 study this fiscal year.

Let us hope that continued study of BAN2401 leads to a truly effective treatment for AD!

A Typical Week with MCI

About a week ago I was contacted by someone from the University of Washington regarding my participation in a study of how people with MCI live their weeks.  The name of the study is “A Typical Week with Mild Cognitive Impairment: A Photo-Elicitation Interview."  Participants were to take five to ten photographs of their activities over a typical week and submit to a one-hour interview regarding the images.  Here's the web site for the study.

I thought this was an interesting idea, so I signed up.  (It helped that I love to take pictures.)  They said they were looking for images that showed how people with MCI learn to cope with their condition.  I thought that my best focus would be on the lifestyle changes that I've made and documented in Beating the Dementia Monster.

I took pictures and selected 10.  They are here.  I explained that the images were intended to highlight the role of physical exercise, Mediterranean diet, social connectivity, organizing daily activities, drug trial participation,  and spiritual coping in the successes that I've experienced in beating (for now, at least) this awful disease.

I was interviewed by the principal investigator this afternoon.  I emphasized the decline I was experiencing in 2015, and told her about how much better I'm doing now.  My hope is that this will be useful to others confronting MCI.

This week I was also approached by someone proposing that I speak to the Washington State Council on Aging during their September in Seatac, Washington.  The person is a member of the council and seems to be able to arrange speakers.  I don't know how serious the suggestion was, but I said that I was willing to do it.