“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.”