title: Longitudinal modeling of age-related memory decline and the APOE epsilon4 effect.
abstract: BACKGROUND
  The APOE epsilon4 allele is associated with the risk of late-onset Alzheimer's disease. The age at which memory decline diverges among persons who are homozygous for the APOE epsilon4 allele, those who are heterozygous for the allele, and noncarriers is unknown.
  
  
  METHODS
  Using local advertisements, we recruited cognitively normal subjects between the ages of 21 and 97 years, who were grouped according to their APOE epsilon4 status. We then followed the subjects with longitudinal neuropsychological testing. Anyone in whom mild cognitive impairment or dementia developed during follow-up was excluded. We compared the rates of decline in predetermined cognitive measures between carriers and noncarriers of the APOE epsilon4 allele, using a mixed model for longitudinal change with age.
  
  
  RESULTS
  We analyzed 815 subjects: 317 APOE epsilon4 carriers (79 who were homozygous for the APOE epsilon4 allele and 238 who were heterozygous) and 498 noncarriers. Carriers, as compared with noncarriers, were generally younger (mean age, 58.0 vs. 61.4 years; P<0.001) and were followed for a longer period (5.3 vs. 4.7 years, P=0.01), with an equivalent duration of formal education (15.4 years) and proportion of women (69%). Longitudinal decline in memory in carriers began before the age of 60 years and showed greater acceleration than in noncarriers (P=0.03), with a possible allele-dose effect (P=0.008). We observed similar although weaker effects on measures of visuospatial awareness and general mental status.
  
  
  CONCLUSIONS
  Age-related memory decline in APOE epsilon4 carriers diverges from that of noncarriers before the age of 60 years, despite ongoing normal clinical status.
authors: Department of Neurology, Mayo Clinic Arizona, Scottsdale, Arizona 85259, USA. caselli.richard@mayo.edu
authors: Richard J
authors: RJ
authors: Caselli
authors: Amylou C
authors: AC
authors: Dueck
authors: David
authors: D
authors: Osborne
authors: Marwan N
authors: MN
authors: Sabbagh
authors: Donald J
authors: DJ
authors: Connor
authors: Geoffrey L
authors: GL
authors: Ahern
authors: Leslie C
authors: LC
authors: Baxter
authors: Steven Z
authors: SZ
authors: Rapcsak
authors: Jiong
authors: J
authors: Shi
authors: Bryan K
authors: BK
authors: Woodruff
authors: Dona E C
authors: DE
authors: Locke
authors: Charlene Hoffman
authors: CH
authors: Snyder
authors: Gene E
authors: GE
authors: Alexander
authors: Rosa
authors: R
authors: Rademakers
authors: Eric M
authors: EM
authors: Reiman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053327:Apolipoprotein E4 / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008568:Memory; D008569:Memory Disorders / Q000175:diagnosis / Q000235:genetics*; D008875:Middle Aged; D009483:Neuropsychological Tests; D055815:Young Adult
chemical_list: D053327:Apolipoprotein E4