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Arch Neurol. 1994 Dec;51(12):1189-92.

Lower cognitive performance in normal older adult male twins carrying the apolipoprotein E epsilon 4 allele.

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  • 1Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis.



Given the strong association of the apolipoprotein E (apoE) allele epsilon 4 with late-onset Alzheimer dementia or multi-infarct dementia, we tested whether normal older adult men with at least one epsilon 4 allele demonstrate subclinical changes in cognition and perform more poorly on tests of cognitive function compared with subjects without the epsilon 4 allele.


Matched-pair design of normal adult male (average age, 63 years) fraternal twins.


Subjects voluntarily participated on an outpatient basis at a research or medical center facility.


Members of the National Heart, Lung, and Blood Institute twin panel third examination previously genotyped for apoE.


Education-adjusted scores on several neuropsychological tests were compared in twins discordant for the apoE epsilon 4 allele. Subjects with documented cerebrovascular disease were excluded.


Among 20 fraternal twin pairs discordant for the presence of epsilon 4, twins with the epsilon 4 allele demonstrated poorer mean performance than their co-twins without the epsilon 4 allele. This relationship was also noted cross-sectionally where age- and education-adjusted scores of 50 individual twin subjects with at least one epsilon 4 allele demonstrated poorer performance compared with 138 individual twins without an epsilon 4 allele.


The apoE epsilon 4 allele may be associated with decreased cognitive function in discordant twin pairs. Our results suggest that epsilon 4 may represent a potential marker for accelerated cognitive aging and such individuals may be at greater risk for development of late-onset Alzheimer dementia or multi-infarct dementia.

[PubMed - indexed for MEDLINE]
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