Why We Sleep

part of the brain on memory, which depended on a different region of the brain.
Was sleep disruption the missing factor?
To test this theory, we had elderly patients with varying levels of amyloid—low
to high—in their brains learn a list of new facts in the evening. The next morning,
after recording their sleep in the laboratory that night, we tested them to see how
effective  their  sleep  had  been  at  cementing  and  thus  holding  on  to  those  new
memories.  We  discovered  a  chain-reaction  effect.  Those  individuals  with  the
highest levels of amyloid deposits in the frontal regions of the brain had the most
severe loss of deep sleep and, as a knock-on consequence, failed to successfully
consolidate those new memories. Overnight forgetting, rather than remembering,
had  taken  place.  The  disruption  of  deep  NREM  sleep  was  therefore  a  hidden
middleman brokering the bad deal between amyloid and memory impairment in
Alzheimer’s disease. A missing link.
These  findings,  however,  were  only  half  of  the  story,  and  admittedly  the  less
important  half.  Our  work  had  shown  that  the  amyloid  plaques  of  Alzheimer’s

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disease may be associated with the loss of deep sleep, but does it work both ways?
Can a lack of sleep actually cause amyloid to build up in your brain to begin with?
If  so,  insufficient  sleep  across  an  individual’s  life  would  significantly  raise  their
risk of developing Alzheimer’s disease.
Around  the  same  time  that  we  were  conducting  our  studies,  Dr.  Maiken
Nedergaard  at  the  University  of  Rochester  made  one  of  the  most  spectacular
discoveries  in  the  field  of  sleep  research  in  recent  decades.  Working  with  mice,
Nedergaard  found  that  a  kind  of  sewage  network  called  the  glymphatic  system
exists within the brain. Its name is derived from the body’s equivalent lymphatic
system, but it’s composed of cells called glia (from the Greek root word for “glue”).
Glial  cells  are  distributed  throughout  your  entire  brain,  situated  side  by  side
with the neurons that generate the electrical impulses of your brain. Just as the
lymphatic  system  drains  contaminants  from  your  body,  the  glymphatic  system
collects and removes dangerous metabolic contaminants generated by the hard
work performed by neurons in your brain, rather like a support team surrounding
an elite athlete.
Although  the  glymphatic  system—the  support  team—is  somewhat  active
during  the  day,  Nedergaard  and  her  team  discovered  that  it  is  during  sleep  that
this  neural  sanitization  work  kicks  into  high  gear.  Associated  with  the  pulsing
rhythm  of  deep  NREM  sleep  comes  a  ten-  to  twentyfold  increase  in  effluent
expulsion from the brain. In what can be described as a nighttime power cleanse,
the  purifying  work  of  the  glymphatic  system  is  accomplished  by  cerebrospinal
fluid that bathes the brain.
Nedergaard  made  a  second  astonishing  discovery,  which  explained  why  the
cerebrospinal  fluid  is  so  effective  in  flushing  out  metabolic  debris  at  night.  The
glial  cells  of  the  brain  were  shrinking  in  size  by  up  to  60  percent  during  NREM
sleep,  enlarging  the  space  around  the  neurons  and  allowing  the  cerebrospinal
fluid to proficiently clean out the metabolic refuse left by the day’s neural activity.
Think of the buildings of a large metropolitan city physically shrinking at night,
allowing municipal cleaning crews easy access to pick up garbage strewn in the
streets,  followed  by  a  good  pressure-jet  treatment  of  every  nook  and  cranny.
When  we  wake  each  morning,  our  brains  can  once  again  function  efficiently
thanks to this deep cleansing.
So  what  does  this  have  to  do  with  Alzheimer’s  disease?  One  piece  of  toxic
debris evacuated by the glymphatic system during sleep is amyloid protein—the
poisonous  element  associated  with  Alzheimer’s  disease.  Other  dangerous
metabolic waste elements that have links to Alzheimer’s disease are also removed

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by  the  cleaning  process  during  sleep,  including  a  protein  called  tau,  as  well  as
stress  molecules  produced  by  neurons  when  they  combust  energy  and  oxygen
during the day. Should you experimentally prevent a mouse from getting NREM
sleep,  keeping  it  awake  instead,  there  is  an  immediate  increase  in  amyloid
deposits within the brain. Without sleep, an escalation of poisonous Alzheimer’s-
related protein accumulated in the brains of the mice, together with several other
toxic  metabolites.  Phrased  differently,  and  perhaps  more  simply,  wakefulness  is
low-level brain damage, while sleep is neurological sanitation.
Nedergaard’s findings completed the circle of knowledge that our findings had
left  unanswered.  Inadequate  sleep  and  the  pathology  of  Alzheimer’s  disease
interact in a vicious cycle. Without sufficient sleep, amyloid plaques build up in
the  brain,  especially  in  deep-sleep-generating  regions,  attacking  and  degrading
them. The loss of deep NREM sleep caused by this assault therefore lessens the
ability  to  remove  amyloid  from  the  brain  at  night,  resulting  in  greater  amyloid
deposition. More amyloid, less deep sleep, less deep sleep, more amyloid, and so
on and so forth.
From this cascade comes a prediction: getting too little sleep across the adult
life  span  will  significantly  raise  your  risk  of  developing  Alzheimer’s  disease.
Precisely  this  relationship  has  now  been  reported  in  numerous  epidemiological
studies,  including  those  individuals  suffering  from  sleep  disorders  such  as
insomnia and sleep apnea.
VIII
Parenthetically, and unscientifically, I have always
found it curious that Margaret Thatcher and Ronald Reagan—two heads of state
that were very vocal, if not proud, about sleeping only four to five hours a night—
both went on to develop the ruthless disease. The current US president, Donald
Trump—also  a  vociferous  proclaimer  of  sleeping  just  a  few  hours  each  night—
may want to take note.
A  more  radical  and  converse  prediction  that  emerges  from  these  findings  is
that,  by  improving  someone’s  sleep,  we  should  be  able  to  reduce  their  risk  of
developing Alzheimer’s disease—or at least delay its onset. Tentative support has
emerged  from  clinical  studies  in  which  middle-  and  older-age  adults  have  had
their  sleep  disorders  successfully  treated.  As  a  consequence,  their  rate  of
cognitive  decline  slowed  significantly,  and  further  delayed  the  onset  of
Alzheimer’s disease by five to ten years.
IX
My own research group is now trying to develop a number of viable methods
for artificially increasing deep NREM sleep that could restore some degree of the
memory  consolidation  function  that  is  absent  in  older  individuals  with  high
amounts of amyloid in the brain. If we can find a method that is cost effective and

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can be scaled up to the population level for repeat use, my goal is prevention. Can
we  begin  supplementing  the  declining  deep  sleep  of  vulnerable  members  of
society  during  midlife,  many  decades  before  the  tipping  point  of  Alzheimer’s
disease is reached, aiming to avert dementia risk later in life? It is an admittedly
lofty ambition, and some would argue a moon shot research goal. But it is worth
recalling that we already use this conceptual approach in medicine in the form of
prescribing  statins  to  higher-risk  individuals  in  their  forties  and  fifties  to  help
prevent cardiovascular disease, rather than having to treat it decades later.
Insufficient  sleep  is  only  one  among  several  risk  factors  associated  with
Alzheimer’s  disease.  Sleep  alone  will  not  be  the  magic  bullet  that  eradicates
dementia. Nevertheless, prioritizing sleep across the life span is clearly becoming
a significant factor for lowering Alzheimer’s disease risk.
I
.  Foundation  for  Traffic  Safety.  “Acute  Sleep  Deprivation  and  Crash  Risk,”  accessed  at
https://www.aaafoundation.org/acute-sleep-deprivation-and-crash-risk
.
II
. Common myths that are of no use in helping to overcome drowsiness while driving include: turning up
the radio, winding down the car window, blowing cold air on your face, splashing cold water on your face,
talking on the phone, chewing gum, slapping yourself, pinching yourself, punching yourself, and promising
yourself a reward for staying awake.
III
. Also known as DEC2.
IV
.  K.  J.  Brower  and  B.  E.  Perron,  “Sleep  disturbance  as  a  universal  risk  factor  for  relapse  in  addictions  to
psychoactive substances,” Medical Hypotheses 74, no. 5 (2010): 928–33; D. A. Ciraulo, J. Piechniczek-Buczek,
and E. N. Iscan, “Outcome predictors in substance use disorders,” Psychiatric Clinics of North America 26, no.
2 (2003): 381–409; J. E. Dimsdale, D. Norman, D. DeJardin, and M. S. Wallace, “The effect of opioids on sleep
architecture,”  Journal  of  Clinical  Sleep  Medicine  3,  no.  1  (2007):  33–36;  E.  F.  Pace-Schott,  R.  Stickgold,  A.
Muzur,  P.  E.  Wigren,  et  al.,  “Sleep  quality  deteriorates  over  a  binge-abstinence  cycle  in  chronic  smoked
cocaine users,” Psychopharmacology (Berl) 179, no. 4 (2005): 873–83; and J. T. Arnedt, D. A. Conroy, and K. J.
Brower, “Treatment options for sleep disturbances during alcohol recovery,” Journal of Addictive Diseases 26,
no. 4 (2007): 41–54.
V
.  K.  J.  Brower  and  B.  E.  Perron,  “Sleep  disturbance  as  a  universal  risk  factor  for  relapse  in  addictions  to
psychoactive substances,” Medical Hypotheses 74, no. 5 (2010): 928–33.
VI
. N. D. Volkow, D. Tomasi, G. J. Wang, F. Telang, et al., “Hyperstimulation of striatal D2 receptors with sleep
deprivation: Implications for cognitive impairment,” NeuroImage 45, no. 4 (2009): 1232–40.
VII
. Cossman had other pearls of wisdom, too, such as “The best way to remember your wife’s birthday is to
forget it once.”
VIII
.  A.  S.  Lim  et  al.,  “Sleep  Fragmentation  and  the  Risk  of  Incident  Alzheimer’s  Disease  and  Cognitive
Decline in Older Persons,” Sleep 36 (2013): 1027–32; A. S. Lim et al., “Modification of the relationship of the
apolipoprotein  E  epsilon4  allele  to  the  risk  of  Alzheimer’s  disease  and  neurofibrillary  tangle  density  by
sleep,” JAMA Neurology 70 (2013): 1544–51; R. S. Osorio et al., “Greater risk of Alzheimer’s disease in older

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adults with insomnia,” Journal of the American Geriatric Society 59 (2011): 559–62; and K. Yaffe et al., “Sleep-
disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women,” JAMA
306 (2011): 613–19.
IX
.  S.  Ancoli-Israel  et  al.,  “Cognitive  effects  of  treating  obstructive  sleep  apnea  in  Alzheimer’s  disease:  a
randomized controlled study,” Journal of the American Geriatric Society 56 (2008): 2076–81; and W.d.S. Moraes
et al., “The effect of donepezil on sleep and REM sleep EEG in patients with Alzheimer’s disease: a double-
blind placebo-controlled study,” Sleep 29 (2006): 199–205.

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CHAPTER 8
Cancer, Heart Attacks, and a Shorter Life
Sleep Deprivation and the Body
I was once fond of saying, “Sleep is the third pillar of good health, alongside diet
and  exercise.”  I  have  changed  my  tune.  Sleep  is  more  than  a  pillar;  it  is  the
foundation on which the other two health bastions sit. Take away the bedrock of
sleep, or weaken it just a little, and careful eating or physical exercise become less
than effective, as we shall see.
Yet the insidious impact of sleep loss on health runs much deeper. Every major
system,  tissue,  and  organ  of  your  body  suffers  when  sleep  becomes  short.  No
aspect of your health can retreat at the sign of sleep loss and escape unharmed.
Like  water  from  a  burst  pipe  in  your  home,  the  effects  of  sleep  deprivation  will
seep into every nook and cranny of biology, down into your cells, even altering
your most fundamental self—your DNA.
Widening  the  lens  of  focus,  there  are  more  than  twenty  large-scale
epidemiological studies that have tracked millions of people over many decades,
all of which report the same clear relationship: the shorter your sleep, the shorter
your life. The leading causes of disease and death in developed nations—diseases
that  are  crippling  health-care  systems,  such  as  heart  disease,  obesity,  dementia,
diabetes, and cancer—all have recognized causal links to a lack of sleep.
This  chapter  describes,  uncomfortably,  the  many  and  varied  ways  in  which
insufficient  sleep  proves  ruinous  to  all  the  major  physiological  systems  of  the
human body: cardiovascular, metabolic, immune, reproductive.
SLEEP LOSS AND THE CARDIOVASCULAR SYSTEM
Unhealthy  sleep,  unhealthy  heart.  Simple  and  true.  Take  the  results  of  a  2011
study that tracked more than half a million men and women of varied ages, races,
and  ethnicities  across  eight  different  countries.  Progressively  shorter  sleep  was
associated  with  a  45  percent  increased  risk  of  developing  and/or  dying  from

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coronary  heart  disease  within  seven  to  twenty-five  years  from  the  start  of  the
study. A similar relationship was observed in a Japanese study of over 4,000 male
workers. Over a fourteen-year period, those sleeping six hours or less were 400 to
500 percent more likely to suffer one or more cardiac arrests than those sleeping
more than six hours. I should note that in many of these studies, the relationship
between  short  sleep  and  heart  failure  remains  strong  even  after  controlling  for
other  known  cardiac  risk  factors,  such  as  smoking,  physical  activity,  and  body
mass. A lack of sleep more than accomplishes its own, independent attack on the
heart.
As  we  approach  midlife,  and  our  body  begins  to  deteriorate  and  health
resilience starts its decline, the impact of insufficient sleep on the cardiovascular
system escalates. Adults forty-five years or older who sleep fewer than six hours a
night  are  200  percent  more  likely  to  have  a  heart  attack  or  stroke  during  their
lifetime,  as  compared  with  those  sleeping  seven  to  eight  hours  a  night.  This
finding  impresses  how  important  it  is  to  prioritize  sleep  in  midlife—which  is
unfortunately the time when family and professional circumstances encourage us
to do the exact opposite.