title: The neuropsychology of normal aging and preclinical Alzheimer's disease.
abstract: OBJECTIVE
  A National Institute on Aging-sponsored work group on preclinical Alzheimer's disease (AD) articulated the need to characterize cognitive differences between normal aging and preclinical AD.
  
  
  METHODS
  Seventy-one apolipoprotein E (APOE) ε4 homozygotes, 194 ε3/ε4 heterozygotes, and 356 ε4 noncarriers age 21 to 87 years who were cognitively healthy underwent neuropsychological testing every 2 years. Longitudinal trajectories of test scores were compared between APOE subgroups.
  
  
  RESULTS
  There was a significant effect of age on all cognitive domains in both APOE ε4 carriers and noncarriers. A significant effect of APOE ε4 gene dose was confined to the memory domain and the Dementia Rating Scale. Cross-sectional comparisons did not discriminate the groups.
  
  
  CONCLUSIONS
  Although cognitive aging patterns are similar in APOE ε4 carriers and noncarriers, preclinical AD is characterized by a significant ε4 gene dose effect that impacts memory and is detectable longitudinally. Preclinical neuropsychological testing strategies should emphasize memory-sensitive measures and longitudinal design.
authors.affiliation: Department of Neurology, Mayo Clinic Arizona, Scottsdale, AZ, USA. Electronic address: caselli.richard@mayo.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Caselli
authors.affiliation: Division of Psychology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
authors.forename: Dona E C
authors.initials: DE
authors.lastname: Locke
authors.affiliation: Department of Biostatistics, Mayo Clinic Arizona, Scottsdale, AZ, USA.
authors.forename: Amylou C
authors.initials: AC
authors.lastname: Dueck
authors.affiliation: Department of Neurology, Mayo Clinic Rochester, MN, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.affiliation: Department of Neurology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
authors.forename: Bryan K
authors.initials: BK
authors.lastname: Woodruff
authors.affiliation: Department of Neurology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
authors.forename: Charlene
authors.initials: C
authors.lastname: Hoffman-Snyder
authors.affiliation: Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.affiliation: Banner Alzheimer's Institute, Phoenix, AZ, USA.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Fleisher
authors.affiliation: Banner Alzheimer's Institute, Phoenix, AZ, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics / Q000523:psychology*; D053327:Apolipoprotein E4 / Q000235:genetics; D003072:Cognition Disorders / Q000209:etiology*; D056344:Executive Function; D005260:Female; D006801:Humans; D007802:Language; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D014796:Visual Perception; D055815:Young Adult
chemical_list: D053327:Apolipoprotein E4
keywords: Age-related memory loss; Apolipoprotein E; Cognitive aging; Longitudinal testing; Mild cognitive impairment; Preclinical Alzheimer's disease
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