26 Scientific American, May 2019THE SCIENCE
OF HEALTHClaudia Wallis is an award-winning science journalist whose
work has appeared in the New York Times, Time, Fortune and the
New Republic. She was science editor at Time and managing editor
of Scientific American Mind.Illustration by Celia KrampienTroubled Sleep
and Dementia
Could better nighttime rest help
delay symptoms of Alzheimer’s?By Claudia WallisAmong the many things that can shatter when Alzheimer’s dis-
ease tightens its grip is the steady rhythm of the body’s sleep-
wake cycle. The problem is so common that one New York City
nursing facility—the Hebrew Home at Riverdale—ran an all-
night program for many years that took in afflicted community
members for a dusk-to-dawn schedule of games, snacks, arts
and crafts, and other activities so that their exhausted families
could get some shut-eye.
Troubled sleep often begins long before dementia becomes
apparent. In recent years research has been heating up on two
key questions: Could disrupted sleep be a reliable early warning
sign that the brain changes of Alzheimer’s have begun? And even
more exciting, though still speculative: Could the onset of the dis-
ease or its progression be slowed by treating sleep-related issues?
The brain pathology of Alzheimer’s gets underway roughly 20
years before symptoms such as memory lapses and confusion
become obvious. Scientists believe the fateful sequence goes
something like this: beta-amyloid, a nerve cell waste product,
starts to accumulate in the spaces around brain cells, eventually
forming the telltale plaques of Alzheimer’s. This is followed by atoxic buildup of tangles of tau protein inside nerve cells, first in
the medial temporal lobe and then spreading to other regions.
These changes lead to the death of neurons, loss of synapses and
general atrophy seen in Alzheimer’s-addled brains and the
observable deterioration of cognition and behavior.
Sleep, as it turns out, impacts both beta-amyloid and tau.
Studies in humans and mice indicate that levels of both proteins
fall during sleep. People who sleep poorly have higher levels of
beta-amyloid and tau in their cerebrospinal fluid—even after a
single bad night. What is perhaps more significant is what hap-
pens over the long term. PET scans show older adults with chron-
ic sleep problems have more beta-amyloid deposited in their
brain. Research published earlier this year in Science revealed
that in a mouse model of Alzheimer’s, lack of sleep promotes the
spread of abnormal tau across certain brain regions. “It suggests
that if there’s a sleep disturbance night after night for some pro-
longed period, it could expose an individual to higher concentra-
tions of these proteins and increase the risk of Alzheimer’s,” says
Brendan Lucey, one of the Science paper’s authors and an assistant
professor of neurology at Washington University in St. Louis.
A 2018 study provides evidence for this cumulative damage
scenario. Using data on 124 older adults participating in a long-
term National Institute on Aging (NIA) study, sleep researcher
Adam Spira and his colleagues at Johns Hopkins University and
the NIA found that people who complained of “excessive daytime
sleepiness” at an average age of 60 were 2.75 times more likely to
have beta-amyloid plaques in their brain some 16 years later.
In another new study, published earlier this year in Science
Translational Medicine, Lucey and his colleagues explored which
part of sleep may be most relevant to Alzheimer’s pathology.
They found that having less of a very deep phase called slow-
wave, non-rapid eye movement sleep, is associated with more
accretion of tau and, to some degree, beta-amyloid. This part of
sleep also happens to be important to memory consolidation.
No one knows for sure what comes first: Do excess beta-amy-
loid and tau impair sleep, or does impaired sleep lead to a build-
up of these proteins? The leading hypothesis is that it goes both
ways in a kind of vicious cycle. For example, Lucey proposes, let’s
say someone “develops sleep apnea, sleeps poorly, increasing
Alzheimer’s pathology, which then worsens their sleep further
and accelerates their pathology.”
Could disrupting this cycle help stave off dementia? It’s too
early to say, but as Spira notes, “there’s a growing interest in com-
ing up with ways to attack poor sleep as a possible way to prevent
Alzheimer’s.” A small study published earlier this year by a team
at the University of California, San Francisco, offers a glimmer of
hope. It looked at 50 older adults with Alzheimer’s, mild cogni-
tive impairment or normal cognition and found that the 25 who
used the drug trazodone as a sleep aid had a significantly slower
cognitive decline than the 25 who did not use the it. Trazodone,
intriguingly, is known to increase slow-wave sleep. Alas, the road
to an Alzheimer’s treatment is littered with disappointment.
Working the sleep angle may prove to be yet another pipe dream,
but it’s hard to imagine it could do much harm.© 2019 Scientific American