title: APOE genotype modifies the relationship between midlife vascular risk factors and later cognitive decline.
abstract: BACKGROUND
  Vascular risk factors have been associated with cognitive decline; however, it remains unclear whether apolipoprotein E (APOE) genotype modifies this relationship. We aimed to further elucidate these relationships and extend previous findings by examining data from a more comprehensive cognitive assessment than used in prior studies.
  
  
  METHODS
  In all, 1436 participants from the prospective Framingham Offspring Cohort Study underwent health examination from 1991 to 1995, followed by a baseline neuropsychological assessment (1999-2003) and a repeat neuropsychological assessment approximately 8 years later (2004-2009). Multivariate linear regression analyses were performed to examine the relationship among midlife vascular risk factors, presence of the APOE ε4 allele, and cognitive change.
  
  
  RESULTS
  APOE genotype significantly modified the associations between both midlife hypertension and cardiovascular disease and decline in language abilities and midlife diabetes and decline in verbal memory, attention, and visuospatial abilities. Associations between increased midlife vascular risk burden and greater cognitive decline were observed among APOE ε4 carriers but not noncarriers.
  
  
  CONCLUSIONS
  The present findings revealed a subgroup at increased risk for cognitive decline (APOE ε4 carriers with midlife exposure to vascular risk factors) and suggest that treatment of vascular risk factors during midlife may reduce the risk of cognitive impairment later in life, particularly among APOE ε4 carriers.
authors.affiliation: Department of Psychiatry, University of California, San Diego School of Medicine, La Jolla, California. Electronic address: kbangen@ucsd.edu.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Bangen
authors.forename: Alexa
authors.initials: A
authors.lastname: Beiser
authors.forename: Lisa
authors.initials: L
authors.lastname: Delano-Wood
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Nation
authors.forename: Melissa
authors.initials: M
authors.lastname: Lamar
authors.forename: David J
authors.initials: DJ
authors.lastname: Libon
authors.forename: Mark W
authors.initials: MW
authors.lastname: Bondi
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
authors.forename: Philip A
authors.initials: PA
authors.lastname: Wolf
authors.forename: Rhoda
authors.initials: R
authors.lastname: Au
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics*; D003072:Cognition Disorders / Q000453:epidemiology* / Q000235:genetics* / Q000523:psychology; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011446:Prospective Studies; D011597:Psychomotor Performance / Q000502:physiology; D012307:Risk Factors; D012959:Socioeconomic Factors; D014652:Vascular Diseases / Q000453:epidemiology* / Q000235:genetics* / Q000523:psychology
chemical_list: D001057:Apolipoproteins E
keywords: Apolipoprotein E; aging; cardiovascular disease; cognition; diabetes; hypertension; vascular risk