Sleep Biomarkers Help Predict the Development of Alzheimer Disease

Middle-aged or older adults who self-report sleep-wake disorders are at an increased risk for incident dementia, mild cognitive impairment, and Alzheimer disease. Dementia in people with mild cognitive impairment and Alzheimer disease who complain of sleep-wake disorders progress faster than those without sleep-wake disorders. Removal of amyloid-beta and tau tangles occurs preferentially in non-rapid eye movement 3 sleep and fragmented or insufficient sleep may lead to accumulation of these neurotoxins even in preclinical stages. Selective atrophy in the medial temporal lobe on brain MRI has been shown to predict impaired coupling of slow oscillations and sleep spindles. Impaired slow wave-spindle coupling has been shown to correlate with impaired overnight memory consolidation. Whereas, a decrease in the amplitude of 0.6 to 1 Hz slow wave activity predicts higher cortical A beta burden on amyloid PET scans. Overexpression of the wake-promoting neurotransmitter orexin may predispose patients with mild cognitive impairment and Alzheimer disease to increased wakefulness, decreasing time they need to clear from the brain the neurotoxic accumulation of amyloid-beta and especially tau. More research exploring these relationships is needed and continuing.