Preclinical memory decline in cognitively normal apolipoprotein E-ε4 homozygotes

Richard John Caselli, Neill R Graff Radford, E. M. Reiman, A. Weaver, D. Osborne, John A Lucas, A. Uecker, Stephen N Thibodeau

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)201-207
Number of pages7
JournalNeurology
Volume53
Issue number1
StatePublished - Jul 13 1999

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Apolipoprotein E4
Homozygote
Heterozygote
Short-Term Memory
Outcome Assessment (Health Care)
Neuropsychological Tests
Memory Disorders
Apolipoproteins E
Atrophy
Research Design
Cross-Sectional Studies
Alleles
Genotype

ASJC Scopus subject areas

  • Neuroscience(all)

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Preclinical memory decline in cognitively normal apolipoprotein E-ε4 homozygotes. / Caselli, Richard John; Graff Radford, Neill R; Reiman, E. M.; Weaver, A.; Osborne, D.; Lucas, John A; Uecker, A.; Thibodeau, Stephen N.

In: Neurology, Vol. 53, No. 1, 13.07.1999, p. 201-207.

Research output: Contribution to journalArticle

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AU - Reiman, E. M.

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AU - Osborne, D.

AU - Lucas, John A

AU - Uecker, A.

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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.

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