Abstract Details

Title Sleep Fragmentation Modifies the Impact of the ApoE4 Allele on the Risk of Incident Alzheimer Disease and Cognitive Decline in Older Persons

Topic Aging and Dementia

Presentation(s) S24 - (-)

Poster/Presentation
Number 004

Objective

Background The ApoE4 allele and sleep fragmentation are both associated with the risk of AD in older persons. We hypothesized that sleep fragmentation may modify the effect of ApoE4 on the risk of incident AD and cognitive decline.

Design/Methods We quantified sleep fragmentation with up to 10 days of actigraphy, and ascertained ApoE genotype in 737 community dwelling older adults without dementia. Subjects then underwent annual evaluation for AD.

Results Over a follow-up period of up to 6 years, 97 individuals developed AD. In a series of Cox proportional hazards models, sleep fragmentation modified the relation between ApoE genotype and the risk of incident AD (interaction estimate=0.43 SE=0.20 p=0.039). In individuals with high (90th percentile) sleep fragmentation ApoE4+/+ was associated with a hazard ratio (HR) of 9.6 for developing AD compared to ApoE4-/-. However, in individuals with low (10th percentile) sleep fragmentation, the HR was reduced to 2.65. In a series of linear mixed effect models, sleep fragmentation also modified the relationship between ApoE genotype and the annual rate of cognitive decline (interaction estimate=-0.064 SE=0.016 p=3.9E-5). In individuals with high sleep fragmentation, ApoE4+/+ was associated with a rate of decline 3.4 times faster than ApoE4-/-. However, in individuals with low sleep fragmentation, this ratio was reduced to 1.3.

Conclusions Sleep fragmentation modifies the impact of the ApoE4 allele on the risk of incident AD and cognitive decline. Management of sleep fragmentation may be a potential means to attenuate the risk of AD and cognitive decline in older individuals carrying the ApoE4 allele.

Authors/Disclosures
Andrew Lim, MD (Univ Toronto / Lim and Hew Med Prof Corp) PRESENTER	Dr. Lim has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai Canada.
	No disclosure on file
	No disclosure on file
Aron S. Buchman, MD (Rush Alzheimer's Disease Center)	No disclosure on file
David A. Bennett, MD (Rush University Medical Center)	Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Origent. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AbbVie. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Study section, DMC, NACA Council with NIH. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a invited lectures with AMCs. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a invited paper with National Academy of Sciences. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a lecture with National Academy of Neuropsychology.
Brian G. Weinshenker, MD, FAAN (University of Virginia Health System)	Dr. Weinshenker has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CANbridge Pharmaceuticals. Dr. Weinshenker has received personal compensation in the range of $0-$499 for serving as a Consultant for CALIBR. Dr. Weinshenker has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon. Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Group (Chugai, Genentech, Roche). Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharmaceuticals. Dr. Weinshenker has received research support from Guthy Jackson Charitable Foundation. Dr. Weinshenker has received intellectual property interests from a discovery or technology relating to health care.

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