Some new ideas about sleep in Alzheimer's disease

In his book, Why We Sleep, Dr. Matthew Walker notes that sleep is controlled by a center in the brain above the level of the nose.  Or maybe several centers.  As we said in Beating the Dementia Monster, all brains atrophy as we age, and Walker notes that the sleep control center is not an exception.  So all of us experience problems with sleep as we age, and the control center atrophies.  However, in neurodegenerative diseases, the atrophy accelerates, and people with Alzheimer's disease have more serious problems with insomnia.  I am not an exception.

But is that the whole story?  In my love-hate relationship with sleep meds, I was surprised to read about the mode of action of the drug Belsomra.  It actually acts on the centers that control wakefulness, not that control sleep.  I didn't know there was such a center (or centers) that control wakefulness, and, as it turns out, these can atrophy as well.  A possible pattern is that insomnia gets worse as Alzheimer's advances, but it later subsides as the "wakefulness" neurons die.  An exception to this pattern may be another disease called "progressive supranuclear palsy (PSP)."  In PSP, affected people do not lose wakefuness neurons, only the ones involved in getting to sleep.  The wakefulness ones stay strong.  So their experience with insomnia is much worse.

So where are these "wakefulness neurons?"  They are located in three tiny areas of the brain, the locus coeruleus, lateral hypothalamic area, and tuberomammillary nucleus.  These produce the neuropeptides (chemical messengers) noradrenaline, orexin, and histamine, respectively that encourage wakefulness.  (These will be in Friday's quiz.)

As I understand it, there are three factors that can affect sleep disturbance: loss of neurons promoting sleep, loss of neurons promoting wakefulness, and changes in the activity of these neurons.  So how do these play together?  There is some interesting recent research.

The journal JAMA Neurology (formerly Journal of the American Medical Association) published some interesting research here.  This research is further discussed here.  The study involved 33 patients with Alzheimer's disease, 20 with PSP, and 32 in a control group.  The study’s findings suggest that loss of wakefulness-promoting neurons at the early stages of neurodegenerative disease may be sufficient to reduce regulation of sleep-wake stability in patients with both Alzheimer's disease and PSP.  The degree of degeneration was measured, in part, by counting neurons in the different parts of the brain on autopsy.  (The mean age of death was 70.  I'm 72.)

There's an apparent inconsistency here.  Dr. Walker is concerned with how Alzheimer's disease shortens sleep, while the more recently published research is about Alzheimer's disease promoting longer sleep.  I Googled for "how does Alzheimer's disease affect sleep."  There was information like this about how Alzheimer's disease creates sleep disturbances that cause people to sleep more, and others like this one that associates it with less sleep.  

How do we reconcile these?  This article is helpful and focuses on the quality of sleep.  But no matter how you cut it, sleeping well is so very important.  Overall, your best bet is good sleep hygiene.