School of Medicine

The Sleep-Dementia Connection

Among the many things that can shatter when Alzheimer’s disease 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 disease 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 a toxic 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 happens over the long term. PET scans show older adults with chronic 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 prolonged period, it could expose an individual to higher concentrations 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.

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