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 APOEϵ4 status is the strongest genetic risk factor for cognitive decline, we assessed whether the ϵ4 allele is associated with stage N3 sleep. Participants were from the population-based Osteoporotic Fractures in Men (MrOS) cohort with polysomnography and APOEϵ4 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 APOEϵ4 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 ϵ4 allele (62±5.2 minutes) compared with 43±1.5 minutes for carriers of one ϵ4 allele (n = 515) and 40±0.8 minutes for ϵ4 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 APOEϵ4 genotype and sleep stage N3 in the elderly. Increased total stage N3 duration among ϵ4/ϵ4 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 ϵ4/ϵ4 carriers.
Bibliographical noteFunding Information:
Funding:TheOsteoporoticFracturesinMen (MrOS)StudyissupportedbyNationalInstitutesof Health(NIH)funding.Thefollowinginstitutes providesupport:theNationalInstituteofArthritis andMusculoskeletalandSkinDiseases(NIAMS), theNationalInstituteonAging(NIA),theNational CenterforResearchResources(NCRR),andNIH RoadmapforMedicalResearchunderthe followinggrantnumbers:U01AR45580,U01 AR45614,U01AR45632,U01AR45647,U01 AR45654,U01AR45583,U01AG18197,U01-AG027810,andUL1RR024140.TheNational Heart,Lung,andBloodInstitute(NHLBI)provides fundingfortheMrOSSleepancillarystudy “OutcomesofSleepDisordersinOlderMen”under thefollowinggrantnumbers:R01HL071194,R01 HL070848,R01HL070847,R01HL070842,R01 HL070841,R01HL070837,R01HL070838,and R01HL070839.NIAMSprovidesfundingforthe MrOSancillarystudy“Replicationofcandidate geneassociationsandbonestrengthphenotypein MrOS”underthegrantnumberR01-AR051124, whichfundedthecreationandmaintenanceof MrOSDNAcollections.Thefundershadnorolein studydesign,datacollectionandanalysis,decision topublish,orpreparationofthemanuscript.
© 2018 Tranah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.