title: Age and apolipoprotein E genotype influence rate of cognitive decline in nondemented elderly.
abstract: OBJECTIVE
  This study examined the impact of age and apolipoprotein E (APOE) genotype on the rate of cognitive decline in nondemented elderly participants in a simulated Alzheimer's disease (AD) primary prevention treatment trial carried out by the Alzheimer's Disease Cooperative Study.
  
  
  METHODS
  Cognitive tests were administered at baseline and at four subsequent annual evaluations to 417 nondemented participants (172 men, 245 women) between the ages of 74 and 93 (M = 79.13 ± 3.34). APOE genotyping was available for 286 of the participants.
  
  
  RESULTS
  Four-year decline was evident on measures of orientation, memory, executive function, and language. Faster decline was evident in APOE ε4+ (a genetic risk factor for AD; n = 73) than in ε4- participants (n = 213), even after controlling for education, gender, ethnicity, and baseline functional and cognitive abilities. This discrepancy increased with age, indicating an Age × Genotype interaction.
  
  
  CONCLUSIONS
  These results are consistent with population-based studies, and extend the findings to a carefully screened sample that meets inclusion and exclusion criteria for an AD primary prevention trial. The interaction between age and APOE genotype on rate of decline suggests that preclinical disease may be overrepresented in older ε4+ individuals. Thus, APOE genotype and age should be considered in the design of AD primary prevention treatment trials.
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093-0948, USA. dsalmon@ucsd.edu
authors.forename: David P
authors.initials: DP
authors.lastname: Salmon
authors.forename: Steven H
authors.initials: SH
authors.lastname: Ferris
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Thomas
authors.forename: Mary
authors.initials: M
authors.lastname: Sano
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Cummings
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D001288:Attention / Q000502:physiology; D003072:Cognition Disorders / Q000235:genetics*; D018672:Community Health Planning; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000235:genetics; D011939:Mental Recall / Q000502:physiology; D008609:Mental Status Schedule; D009483:Neuropsychological Tests; D009949:Orientation / Q000502:physiology; D014796:Visual Perception
chemical_list: D001057:Apolipoproteins E