title: Influence of Alzheimer disease family history and genetic risk on cognitive performance in healthy middle-aged and older people.
abstract: OBJECTIVE
  Identification of risk factors for Alzheimer disease (AD) is critical for establishing effective diagnostic and therapeutic strategies. Carrying the ε4 allele of the apolipoprotein E gene (APOE4) and having a family history of the disease are two such factors, with family history risk reflecting additional yet unknown or rarely studied genetic and perhaps nongenetic risks. Our aim was to determine the influence of APOE genotype and family history status on cognitive performance in healthy individuals.
  
  
  METHODS
  Longitudinal study.
  
  
  METHODS
  Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles.
  
  
  METHODS
  Seventy-two cognitively healthy middle-aged and older people (mean age ± SD: 62 ± 9 years).
  
  
  METHODS
  Neuropsychological examinations at baseline and after 2 years.
  
  
  RESULTS
  Subjects with a family history of AD had lower baseline scores in processing speed, executive functioning, memory encoding, and delayed memory when compared with those without a family history. The family history risk factor did not influence degree of cognitive decline over time. By contrast, baseline cognitive performance did not vary according to APOE4 carrier status. Non-APOE4 carriers showed improved cognitive performance in the memory domains at follow-up, while performance of APOE4 carriers did not change.
  
  
  CONCLUSIONS
  Our data highlight the unique contributions of each risk factor to cognitive performance in healthy people. Both factors should be modeled in neuropsychological assessments of people at risk for AD.
authors.affiliation: Center for Cognitive Neurosciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Donix
authors.forename: Linda M
authors.initials: LM
authors.lastname: Ercoli
authors.forename: Prabha
authors.initials: P
authors.lastname: Siddarth
authors.forename: Jesse A
authors.initials: JA
authors.lastname: Brown
authors.forename: Laurel
authors.initials: L
authors.lastname: Martin-Harris
authors.forename: Alison C
authors.initials: AC
authors.lastname: Burggren
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Miller
authors.forename: Gary W
authors.initials: GW
authors.lastname: Small
authors.forename: Susan Y
authors.initials: SY
authors.lastname: Bookheimer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000523:psychology*; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D003071:Cognition; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics / Q000523:psychology; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E