Why We Sleep

participants had before they were tested, the better their memory was. All except
another  sub-group  of  participants.  Like  the  subjects  in  the  third  group,  these
participants  learned  the  task  on  the  first  day,  and  learned  it  just  as  well.  They
were then tested three nights later, just like the third group above. The difference
was  that  they  were  deprived  of  sleep  the  first  night  after  learning  and  were  not
tested the following day. Instead, Stickgold gave them two full recovery nights of
sleep  before  testing  them.  They  showed  absolutely  no  evidence  of  a  memory
consolidation improvement. In other words, if you don’t sleep the very first night
after learning, you lose the chance to consolidate those memories, even if you get
lots of “catch-up” sleep thereafter. In terms of memory, then, sleep is not like the
bank. You cannot accumulate a debt and hope to pay it off at a later point in time.
Sleep  for  memory  consolidation  is  an  all-or-nothing  event.  It  is  a  concerning
result in our 24/7, hurry-up, don’t-wait society. I feel another op-ed coming on . . .
SLEEP AND ALZHEIMER’S DISEASE
The  two  most  feared  diseases  throughout  developed  nations  are  dementia  and
cancer. Both are related to inadequate sleep. We will address the latter in the next
chapter  regarding  sleep  deprivation  and  the  body.  Regarding  the  former,  which
centers on the brain, a lack of sleep is fast becoming recognized as a key lifestyle
factor determining whether or not you will develop Alzheimer’s disease.
The condition, originally identified in 1901 by German physician Dr. Aloysius
Alzheimer, has become one of the largest public health and economic challenges
of  the  twenty-first  century.  More  than  40  million  people  suffer  from  the
debilitating  disease.  That  number  has  accelerated  as  the  human  life  span  has
stretched,  but  also,  importantly,  as  total  sleep  time  has  decreased.  One  in  ten
adults  over  the  age  of  sixty-five  now  suffers  from  Alzheimer’s  disease.  Without
advances in diagnosis, prevention, and therapeutics, the escalation will continue.
Sleep  represents  a  new  candidate  for  hope  on  all  three  of  these  fronts:
diagnosis,  prevention,  and  therapeutics.  Before  discussing  why,  let  me  first
describe how sleep disruption and Alzheimer’s disease are causally linked.
As we learned in chapter 5, sleep quality—especially that of deep NREM sleep
—deteriorates as we age. This is linked to a decline in memory. However, if you
assess a patient with Alzheimer’s disease, the disruption of deep sleep is far more

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exaggerated. More telling, perhaps, is the fact that sleep disturbance precedes the
onset of Alzheimer’s disease by several years, suggesting that it may be an early-
warning sign of the condition, or even a contributor to it. Following diagnosis, the
magnitude  of  sleep  disruption  will  then  progress  in  unison  with  the  symptom
severity  of  the  Alzheimer’s  patient,  further  suggesting  a  link  between  the  two.
Making matters worse, over 60 percent of patients with Alzheimer’s disease have
at least one clinical sleep disorder. Insomnia is especially common, as caregivers
of a loved one with Alzheimer’s disease will know all too well.
It  was  not  until  relatively  recently,  however,  that  the  association  between
disturbed  sleep  and  Alzheimer’s  disease  was  realized  to  be  more  than  just  an
association. While much remains to be understood, we now recognize that sleep
disruption and Alzheimer’s disease interact in a self-fulfilling, negative spiral that
can initiate and/or accelerate the condition.
Alzheimer’s  disease  is  associated  with  the  buildup  of  a  toxic  form  of  protein
called  beta-amyloid,  which  aggregates  in  sticky  clumps,  or  plaques,  within  the
brain.  Amyloid  plaques  are  poisonous  to  neurons,  killing  the  surrounding  brain
cells. What is strange, however, is that amyloid plaques only affect some parts of
the brain and not others, the reasons for which remain unclear.
What struck me about this unexplained pattern was the location in the brain
where amyloid accumulates early in the course of Alzheimer’s disease, and most
severely  in  the  late  stages  of  the  condition.  That  area  is  the  middle  part  of  the
frontal lobe—which, as you will remember, is the same brain region essential for
the electrical generation of deep NREM sleep in healthy young individuals. At that
time,  we  did  not  understand  if  or  why  Alzheimer’s  disease  caused  sleep
disruption,  but  simply  knew  that  they  always  co-occurred.  I  wondered  whether
the  reason  patients  with  Alzheimer’s  disease  have  such  impaired  deep  NREM
sleep  was,  in  part,  because  the  disease  erodes  the  very  region  of  the  brain  that
normally generates this key stage of slumber.
I  joined  forces  with  Dr.  William  Jagust,  a  leading  authority  on  Alzheimer’s
disease, at the University of California, Berkeley. Together, our research teams set
about  testing  this  hypothesis.  Several  years  later,  having  assessed  the  sleep  of
many older adults with varying degrees of amyloid buildup in the brain that we
quantified  with  a  special  type  of  PET  scan,  we  arrived  at  the  answer.  The  more
amyloid  deposits  there  were  in  the  middle  regions  of  the  frontal  lobe,  the  more
impaired the deep-sleep quality was in that older individual. And it was not just a
general loss of deep sleep, which is common as we get older, but the very deepest
of  the  powerful  slow  brainwaves  of  NREM  sleep  that  the  disease  was  ruthlessly

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eroding. This distinction was important, since it meant that the sleep impairment
caused by amyloid buildup in the brain was more than just “normal aging.” It was
unique—a departure from what is otherwise the signature of sleep decline as we
get older.
We  are  now  examining  whether  this  very  particular  “dent”  in  sleeping
brainwave activity represents an early identifier of those who are at greatest risk
of developing Alzheimer’s disease, years in advance. If sleep does prove to be an
early  diagnostic  measure—especially  one  that  is  relatively  cheap,  noninvasive,
and can be easily obtained in a large number of individuals, unlike costly MRI or
PET scans—then early intervention becomes possible.
Building on these findings, our recent work has added a key piece in the jigsaw
puzzle of Alzheimer’s disease. We have discovered a new pathway through which
amyloid plaques may contribute to memory decline later in life: something that
has been largely missing in our understanding of how Alzheimer’s disease works. I
mentioned that the toxic amyloid deposits only accumulate in some parts of the
brain and not others. Despite Alzheimer’s disease being typified by memory loss,
the  hippocampus—that  key  memory  reservoir  in  the  brain—is  mysteriously
unaffected  by  amyloid  protein.  This  question  has  so  far  baffled  scientists:  How
does  amyloid  cause  memory  loss  in  Alzheimer’s  disease  patients  when  amyloid
itself  does  not  affect  memory  areas  of  the  brain?  While  other  aspects  of  the
disease  may  be  at  play,  it  seemed  plausible  to  me  that  there  was  a  missing
intermediary  factor—one  that  was  transacting  the  influence  of  amyloid  in  one