In Alzheimer disease, increased wake fragmentation found in those with lower hypocretin-1

Abstract

Regulation of wakefulness is often disturbed in Alzheimer disease (AD). We examined CSF concentrations of hypocretin-1, a wake-stimulating peptide, in 16 patients with AD and simultaneously recorded a week of at-home sleep. Although hypocretin-1 concentrations were normal, fragmentation of daytime wake was elevated in those with low hypocretin-1 levels ( r = −0.64, p < 0.05, number of naps; r = −0.62, p < 0.05, napping hours; r = −0.63, p < 0.05, locomotor rhythm amplitude). Lower hypocretin-1 levels may be permissive for, or a consequence of, increased wake fragmentation in AD. Sleep disruption is commonly observed in older individuals with Alzheimer disease (AD)1 and may predict rapidity of cognitive decline. The biologic basis for sleep dysregulation is unknown but may be related to the degeneration of the cholinergic fibers critical to both cognition and control of sleep. A recently discovered hypothalamic neuropeptide, hypocretin-1, has been hypothesized to be involved in consolidation of wakefulness into a single daily episode2 or in consolidation of both nocturnal sleep and diurnal wake.3 Failure of this consolidation process may underlie some sleep disturbances observed in AD.1 Although previous studies have determined that there may be normal levels of hypocretin-1 in AD,4,5 we sought to determine whether there were associations between …