Preclinical memory decline in cognitively normal apolipoprotein E-epsilon4 homozygotes.
OBJECTIVE
To determine, in a cross-sectional evaluation of nondemented individuals, if age-related memory decline is influenced by apolipoprotein E (apoE) genotype.


BACKGROUND
The apoE-4 allele is an important risk factor for AD. PET in cognitively normal apoE-4 carriers (mean age, 56 years) shows reduced cerebral metabolism suggestive of very early AD that precedes clinically evident memory loss or MRI-based hippocampal atrophy.


METHODS
Tests of immediate and delayed recall (primary outcome measures) and other neuropsychological measures (secondary outcome measures) were given to three genetically defined groups of cognitively normal individuals (age, 49 to 69 years) including apoE-4 homozygotes (n = 25), apoE-4 heterozygotes (n = 25, all epsilon3/4), and apoE-4 noncarriers (n = 50). Groups were matched for age, gender, and educational background. Cross-sectional comparisons between the genetic subgroups of the relationship between age and test score were performed for each neuropsychological measure.


RESULTS
There were no intergroup differences in mean scores on any neuropsychological measure, but tests sensitive to immediate and delayed recall showed a significant negative correlation with age in the apoE-4 homozygote group relative to the noncarrier group.


CONCLUSIONS
Consistent with previous neuropsychological studies of early AD, this cross-sectional study suggests that age-related memory decline occurs earlier in cognitively healthy apoE-4 homozygotes than in apoE-4 heterozygotes and noncarriers, and precedes clinically detectable AD.
Department of Neurology, Mayo Clinic Scottsdale, AZ 85259, USA.
R J
RJ
Caselli
N R
NR
Graff-Radford
E M
EM
Reiman
A
A
Weaver
D
D
Osborne
J
J
Lucas
A
A
Uecker
S N
SN
Thibodeau
D000367:Age Factors; D000368:Aged; D000483:Alleles; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000502:physiology*; D003071:Cognition / Q000502:physiology*; D005260:Female; D007839:Functional Laterality; D006580:Genetic Carrier Screening; D006720:Homozygote; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics*; D011939:Mental Recall; D008875:Middle Aged; D009483:Neuropsychological Tests; D012044:Regression Analysis
D053327:Apolipoprotein E4; D001057:Apolipoproteins E