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Lower Cognitive Performance in Normal Older Adult Male Twins Carrying the Apolipoprotein E 4 Allele

Terry Reed, PhD; Dorit Carmelli, PhD; Gary E. Swan, PhD; John C. S. Breitner, MD; Kathleen A. Welsh, PhD; Gail P. Jarvik, MD; Samir Deeb, PhD; Johan Auwerx, MD

Arch Neurol. 1994;51(12):1189-1192.

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

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

Conclusions
The apoE 4 allele may be associated with decreased cognitive function in discordant twin pairs. Our results suggest that 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.

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).

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