title: Preclinical cognitive decline in late middle-aged asymptomatic apolipoprotein E-e4/4 homozygotes: a replication study.
abstract: In a previous cross-sectional study of 100 asymptomatic individuals aged 49-69, we reported age-related decline in immediate and delayed memory that was steeper in apolipoprotein E (apoE)-e4/4 homozygotes than in members of other genetic subgroups. These findings were preliminarily based upon the statistical problem of multiple comparisons. We therefore sought to replicate these findings in a new cohort. From 1998 to 2000, 80 asymptomatic residents of Maricopa County, AZ were recruited through newspaper ads. 20 apoE-e4/4 homozygotes, 20 e3/4 heterozygotes, and 40 e4 noncarriers were matched (1:1:2) by age, gender, and years of education. All had normal neurologic and psychiatric examinations, including Folstein minimental status exam (MMSE) and Hamilton depression scale, and underwent a battery of neuropsychological tests identical to those in our previous study. The groups were well-matched for age (55.9+/-5.9 years), gender (60% women), and education (15.9+/-2.2 years), and were demographically similar to our previous cohort. Complex figure test recall was lower in e3/4 heterozygotes than noncarriers, but there was no significant difference between e4/4 homozygotes and noncarriers. There were no other significant differences in mean test scores between groups, but Wechsler adult intelligence scale-revised (WAIS-R) digit span showed a significant negative correlation with age in the e4/4 homozygote group relative to e4 noncarriers (p=0.008) as we had found in our previous study. In conclusion, we found a significant negative correlation of WAIS-R digit span with age in apoE-e4/4 homozygotes relative to e4 noncarriers in two separate cohorts, possibly reflecting an age-related effect on frontal lobe function in this genetic subgroup.
authors.affiliation: Department of Neurology, Mayo Clinic Scottsdale, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA. Caselli.Richard@Mayo.edu
authors.forename: R J
authors.initials: RJ
authors.lastname: Caselli
authors.forename: D
authors.initials: D
authors.lastname: Osborne
authors.forename: E M
authors.initials: EM
authors.lastname: Reiman
authors.forename: J G
authors.initials: JG
authors.lastname: Hentz
authors.forename: C J
authors.initials: CJ
authors.lastname: Barbieri
authors.forename: A M
authors.initials: AM
authors.lastname: Saunders
authors.forename: J
authors.initials: J
authors.lastname: Hardy
authors.forename: N R
authors.initials: NR
authors.lastname: Graff-Radford
authors.forename: G R
authors.initials: GR
authors.lastname: Hall
authors.forename: G E
authors.initials: GE
authors.lastname: Alexander
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics*; D015331:Cohort Studies; D003863:Depression; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008568:Memory; D008875:Middle Aged; D009483:Neuropsychological Tests
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E