Apoe Epsilon 4 And Slow Wave Sleep In Older Adults

Slow wave (or stage N3) sleep has been linked to a variety of cognitive processes. However, the role of stage N3 in the elderly is debated. The link between stage N3 and episodic memory may be weakened or changed in the older adult population, possibly due to several altered mechanisms impacting the cellular structure of the brain. The bases for the agerelated dissociation between stage N3 and cognition are not understood. Since APOE epsilon 4 status is the strongest genetic risk factor for cognitive decline, we assessed whether the epsilon 4 allele is associated with stage N3 sleep. Participants were from the population-based Osteoporotic Fractures in Men (MrOS) cohort with polysomnography and APOE epsilon 4 genotype data (n = 2,302, 100% male, mean age 76.6 years). Sleep stages were objectively measured using overnight in-home polysomnography and central electroencephalogram data were used to score stage N3 sleep. Cognitive function was assessed using the Modified Mini Mental State Exam (3MS). The APOE rs429358 single nucleotide polymorphism, which defines the APOE epsilon 4 allele, was genotyped using a custom genotyping array. Total time in stage N3 sleep was significantly higher (p< 0.0001) among the 40 MrOS participants carrying two copies of the e4 allele (62 +/- 5.2 minutes) compared with 43 +/- 1.5 minutes for carriers of one epsilon 4 allele (n = 515) and 40 +/- 0.8 minutes for epsilon 4 non-carriers (n = 1747). All results were independent of sleep efficiency, number of sleep cycles, and apnea hypopnea index. These findings support an association between APOE epsilon 4 genotype and sleep stage N3 in the elderly. Increased total stage N3 duration among e4/ e4 carriers does not appear to reflect compensation for prior cognitive decline and may reflect overactive downscaling of synapses during sleep. If confirmed, these results might in part explain the high risk of agerelated cognitive decline and AD among APOE epsilon 4/epsilon 4 carriers.