title: Cerebrovascular risk factors and preclinical memory decline in healthy APOE ε4 homozygotes.
abstract: OBJECTIVE
  To characterize the effects of cerebrovascular (CV) risk factors on preclinical memory decline in cognitively normal individuals at 3 levels of genetic risk for Alzheimer disease (AD) based on APOE genotype.
  
  
  METHODS
  We performed longitudinal neuropsychological testing on an APOE ε4 enriched cohort, ages 21-97. The long-term memory (LTM) score of the Auditory Verbal Learning Test (AVLT) was the primary outcome measure. Any of 4 CV risk factors (CVany), including hypercholesterolemia (CHOL), prior cigarette use (CIG), diabetes mellitus (DM), and hypertension (HTN), was treated as a dichotomized variable. We estimated the longitudinal effect of age using statistical models that simultaneously modeled the cross-sectional and longitudinal effects of age on AVLT LTM by APOE genotype, CVany, and the interaction between the two.
  
  
  RESULTS
  A total of 74 APOE ε4 homozygotes (HMZ), 239 ε4 heterozygotes (HTZ), and 494 ε4 noncarriers were included. APOE ε4 carrier status showed a significant quadratic effect with age-related LTM decline in all models as previously reported. CVany was associated with further longitudinal AVLT LTM decline in APOE ε4 carriers (p=0.02), but had no effect in noncarriers. When ε4 HTZ and HMZ were considered separately, there was a striking effect in HMZ (p<0.001) but not in HTZ. In exploratory analyses, significant deleterious effects were found for CIG (p=0.001), DM (p=0.03), and HTN (p=0.05) in APOE ε4 carriers only that remained significant only for CIG after correction for multiple comparisons.
  
  
  CONCLUSIONS
  CV risk factors influence age-related memory decline in APOE ε4 HMZ.
authors.affiliation: Department of Neurology, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA. Caselli.Richard@Mayo.edu
authors.forename: R J
authors.initials: RJ
authors.lastname: Caselli
authors.forename: A C
authors.initials: AC
authors.lastname: Dueck
authors.forename: D E C
authors.initials: DE
authors.lastname: Locke
authors.forename: M N
authors.initials: MN
authors.lastname: Sabbagh
authors.forename: G L
authors.initials: GL
authors.lastname: Ahern
authors.forename: S Z
authors.initials: SZ
authors.lastname: Rapcsak
authors.forename: L C
authors.initials: LC
authors.lastname: Baxter
authors.forename: R
authors.initials: R
authors.lastname: Yaari
authors.forename: B K
authors.initials: BK
authors.lastname: Woodruff
authors.forename: C
authors.initials: C
authors.lastname: Hoffman-Snyder
authors.forename: R
authors.initials: R
authors.lastname: Rademakers
authors.forename: S
authors.initials: S
authors.lastname: Findley
authors.forename: E M
authors.initials: EM
authors.lastname: Reiman
mesh_terms: D000328:Adult; D000375:Aging / Q000235:genetics / Q000523:psychology*; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics* / Q000523:psychology*; D053327:Apolipoprotein E4 / Q000235:genetics*; D002560:Cerebrovascular Circulation / Q000235:genetics*; D003071:Cognition; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008569:Memory Disorders / Q000150:complications / Q000235:genetics*; D057567:Memory, Long-Term; D008875:Middle Aged; D009483:Neuropsychological Tests; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4