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December 1994

Lower Cognitive Performance in Normal Older Adult Male Twins Carrying the Apolipoprotein E ε4 Allele

Author Affiliations

From the Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis (Dr Reed); Health Sciences Program, SRI International (formerly Stanford Research Institute), Menlo Park, Calif (Drs Carmelli and Swan); Department of Psychiatry and the Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC (Drs Breitner and Welsh); Division of Medical Genetics, Department of Medicine, University of Washington Medical Center, Seattle (Drs Jarvik and Deeb); and Laboratoire de Biologie des Régulations chez les Eucaryotes, Institut Pasteur, Lille, France (Dr Auwerx).

Arch Neurol. 1994;51(12):1189-1192. doi:10.1001/archneur.1994.00540240033012

Objective:  Given the strong association of the apolipoprotein E (apoE) allele ε4 with late-onset Alzheimer dementia or multi-infarct dementia, we tested whether normal older adult men with at least one ε4 allele demonstrate subclinical changes in cognition and perform more poorly on tests of cognitive function compared with subjects without the ε4 allele.

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

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

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

Main Outcome Measure:  Education-adjusted scores on several neuropsychological tests were compared in twins discordant for the apoE ε4 allele. Subjects with documented cerebrovascular disease were excluded.

Results:  Among 20 fraternal twin pairs discordant for the presence of ε4, twins with the ε4 allele demonstrated poorer mean performance than their co-twins without the ε4 allele. This relationship was also noted crosssectionally where age- and education-adjusted scores of 50 individual twin subjects with at least one ε4 allele demonstrated poorer performance compared with 138 individual twins without an ε4 allele.

Conclusions:  The apoE ε4 allele may be associated with decreased cognitive function in discordant twin pairs. Our results suggest that ε4 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.