title: IDE (rs6583817) polymorphism and pulse pressure are independently and interactively associated with level and change in executive function in older adults.
abstract: OBJECTIVE
  We report a gene × environment (health) study focusing on concurrent performance and longitudinal change in a latent-variable executive function (EF) phenotype. Specifically, we tested the independent and interactive effects of a recently identified insulin degrading enzyme genetic polymorphism (IDE rs6583817) and pulse pressure (PP; one prominent aging-related vascular health indicator) across up to 9 years of EF data in a sample of older adults from the Victoria Longitudinal Study. Both factors vary across a continuum of risk-elevating to risk-reducing and have been recently linked to normal and impaired cognitive aging.
  
  
  METHODS
  We assembled a genotyped and typically aging group of older adults (n = 599, M age = 66 years at baseline), following them for up to 3 longitudinal waves (M interval = 4.4 years). We used confirmatory factor analyses, latent growth modeling, and path analyses to pursue 3 main research goals.
  
  
  RESULTS
  First, the EF single factor model was confirmed comprising 4 executive function tasks and it demonstrated measurement invariance across the waves. Second, older adults with the major IDE G allele exhibited better EF outcomes than homozygotes for the minor A allele at the centering age of 75 years. Adults with higher PP performed more poorly on EF tasks at age 75 years and exhibited greater EF longitudinal decline. Third, gene × health interaction analyses showed that worsening vascular health (higher PP) differentially affected EF performance in older adults with the IDE G allele.
  
  
  CONCLUSIONS
  Genetic interaction analyses can reveal differential and magnifying effects on cognitive phenotypes in aging. In the present case, pulse pressure is confirmed as a risk factor for concurrent and changing cognitive health in aging, but the effects operate differently across the risk and protective allelic distribution of this IDE gene.
authors.affiliation: Department of Psychology, University of Alberta.
authors.forename: G Peggy
authors.initials: GP
authors.lastname: McFall
authors.affiliation: Department of Psychology, University of Alberta.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Wiebe
authors.affiliation: Centre for Prions and Protein Folding Diseases, University of Alberta.
authors.forename: David
authors.initials: D
authors.lastname: Vergote
authors.affiliation: Centre for Neuroscience, University of Alberta.
authors.forename: Jack
authors.initials: J
authors.lastname: Jhamandas
authors.affiliation: Centre for Neuroscience, University of Alberta.
authors.forename: David
authors.initials: D
authors.lastname: Westaway
authors.affiliation: Department of Psychology, University of Alberta.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Dixon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000502:physiology* / Q000523:psychology; D000483:Alleles; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology*; D001955:British Columbia; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000235:genetics / Q000503:physiopathology; D056344:Executive Function / Q000502:physiology*; D005163:Factor Analysis, Statistical; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007339:Insulysin / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests
chemical_list: D007339:Insulysin