title: Risk-reducing Apolipoprotein E and Clusterin genotypes protect against the consequences of poor vascular health on executive function performance and change in nondemented older adults.
abstract: We examined independent and cumulative effects of 2 Alzheimer's-related genetic polymorphisms, Apolipoprotein E (APOE) and Clusterin (CLU), in relation to the deleterious effects of poor vascular health (pulse pressure [PP]) on executive function (EF) performance and change in nondemented older adults. Using a sample (n = 593; age range = 53-95 years) from the Victoria Longitudinal Study, we applied latent growth modeling to test the effect of PP, as moderated by APOE and CLU, on an EF latent variable. EF was affected by higher levels of PP but differentially less so for carriers of low-risk alleles (APOE ɛ2+; CLU TT) than for moderate- or high-risk alleles (APOE ɛ2-; CLU C+). The cumulative genetic risk of APOE plus CLU provided similar moderation of PP level effects on EF. Future research may focus on how APOE and CLU might provide different but complementary contributions to predicting EF level and change. Vascular health risk in synergistic association with risk-related polymorphisms can elucidate the neurobiological underpinnings of cognitive trajectories in nondemented aging.
authors.affiliation: Department of Psychology, University of Alberta, Edmonton, Canada; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Canada.
authors.forename: G Peggy
authors.initials: GP
authors.lastname: McFall
authors.affiliation: Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Canada.
authors.forename: Shraddha
authors.initials: S
authors.lastname: Sapkota
authors.affiliation: Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Canada.
authors.forename: Kirstie L
authors.initials: KL
authors.lastname: McDermott
authors.affiliation: Department of Psychology, University of Alberta, Edmonton, Canada; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Canada. Electronic address: rdixon@ualberta.ca.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Dixon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D001794:Blood Pressure / Q000502:physiology*; D051152:Clusterin / Q000235:genetics*; D056344:Executive Function / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012306:Risk
chemical_list: D001057:Apolipoproteins E; D051152:Clusterin
keywords: Apolipoprotein E; Clusterin; Executive function; Pulse pressure; Victoria Longitudinal Study