TY - JOUR
T1 - Preclinical memory decline in cognitively normal apolipoprotein E-ε4 homozygotes
AU - Caselli, Richard J.
AU - Graff-Radford, N. R.
AU - Reiman, E. M.
AU - Weaver, A.
AU - Osborne, D.
AU - Lucas, J.
AU - Uecker, A.
AU - Thibodeau, S. N.
PY - 1999/7/13
Y1 - 1999/7/13
N2 - 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 ε3/4), 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. Conclusion: 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.
AB - 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 ε3/4), 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. Conclusion: 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.
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U2 - 10.1212/wnl.53.1.201
DO - 10.1212/wnl.53.1.201
M3 - Article
C2 - 10408560
AN - SCOPUS:0033551459
SN - 0028-3878
VL - 53
SP - 201
EP - 207
JO - Neurology
JF - Neurology
IS - 1
ER -