title: Relationship of cognitive reserve and APOE status to the emergence of clinical symptoms in preclinical Alzheimer's disease.
abstract: The APOE ε4 allele increases the risk of developing Alzheimer's disease, whereas the APOE ε2 allele reduces risk. We examined whether cognitive reserve (CR), as measured by an index consisting of education, reading, and vocabulary, modifies these associations. CR was measured at baseline in 257 cognitively normal individuals (mean age 57.2 years) who have been followed for up to 17 years (mean follow-up = 9.2 years). Cox regression models showed that CR and APOE ε4 independently affected the risk of progressing from normal cognition to onset of clinical symptoms: CR reduced risk by about 50% in both ε4 carriers and non-carriers, while ε4 increased risk by about 150%. In contrast, APOE ε2 interacted with CR, such that CR was more protective in ε2 carriers than non-carriers. This suggests that individuals with an ε2 genotype may disproportionately benefit from lifetime experiences that enhance cognition.
authors.affiliation: a Department of Neurology , The Johns Hopkins University School of Medicine , Baltimore , MD , USA.
authors.forename: Corinne
authors.initials: C
authors.lastname: Pettigrew
authors.forename: Anja
authors.initials: A
authors.lastname: Soldan
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Mei-Cheng
authors.initials: MC
authors.lastname: Wang
authors.forename: Ola A
authors.initials: OA
authors.lastname: Selnes
authors.forename: Abhay
authors.initials: A
authors.lastname: Moghekar
authors.forename: Richard
authors.initials: R
authors.lastname: O'Brien
authors.forename: Marilyn
authors.initials: M
authors.lastname: Albert
authors.lastname: The Biocard Research Team
mesh_terms: D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics*; D053329:Apolipoprotein E2 / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D058245:Cognitive Reserve / Q000502:physiology*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011932:Reading; D012044:Regression Analysis; D012307:Risk Factors; D014825:Vocabulary
chemical_list: D053329:Apolipoprotein E2; D053327:Apolipoprotein E4