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[P4–077]: ALZHEIMER's BIOMARKERS INTERACT DYNAMICALLY TO PREDICT COGNITIVE TRAJECTORIES DIFFERENTIALLY FOR COGNITIVELY EXCEPTIONAL, NORMAL, AND IMPAIRED GROUPS
Author(s) -
McFall G. Peggy,
Dixon Roger A.
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.1942
Subject(s) - cognition , effects of sleep deprivation on cognitive performance , biomarker , cognitive decline , moderation , psychology , oncology , cognitive test , disease , audiology , medicine , gerontology , dementia , neuroscience , biology , social psychology , biochemistry
Background:Having an APOE-e4 allele is a risk factor for Alzheimer’s Disease (AD), but some data also suggest that it may have protective effects earlier in life. Low education is another known risk factor for AD. We examined whether parental education interacted with risk genes for AD to predict later cognitive performance. Methods: Participants were 1048 white, non-Hispanic community-dwelling men of European ancestry average age 62. Genetic risk was evaluated with two indicators: the APOE genotype and an AD polygenic risk score (AD-PRS) derived from the International Genomics of Alzheimer’s Project data. Here we used the AD-PRS excluding SNPs in the APOE region. APOEe4 status was categorized as having no e4 allele (e4-; 71%) versus any (e4+; 29%). Parental education was operationalized as having at least one (76%) or neither parent (24%) complete high school. We controlled for non-independence of twins in mixed models, adjusted for the first 3 principal components from the SNP data, and age. Cognitive performance was assessed with a measure of general cognitive ability at ages 20 and 62 and nine specific cognitive abilities at age 62. Results:Both parental education and the parental education by APOE genotype interaction were significantly associated with GCA at ages 20 and 62, as well as with five out of nine cognitive abilities at age 62 (Abstract Reasoning, Episodic Memory, Processing Speed, Working Memory, and Visual Spatial Ability). The interactions indicated that being e4+ when neither parent had a high school education was associated with significantly lower cognitive ability scores; however, when one parent had at least a high school education, participants who were ε4+ showed better cognitive function than their ε4counterparts, even including general cognitive ability at age 20. The AD-PRS by parental education interaction was significant for only three cognitive measures. Conclusions: As expected, presence of the APOE-e4 allele under disadvantaged childhood conditions was associated with poorer performance. Consistent with the differential susceptibility hypothesis, however, in more favorable contexts the presence of an ε4 allele appeared to be advantageous. In addition, the age 20 results suggest that these cognitive differences were apparent relatively early in development.