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


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


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


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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Reed
T
T
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis.
Carmelli
D
D
Swan
G E
GE
Breitner
J C
JC
Welsh
K A
KA
Jarvik
G P
GP
Deeb
S
S
Auwerx
J
J
D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics / Q000523:psychology; D001057:Apolipoproteins E / Q000235:genetics*; D003071:Cognition; D003072:Cognition Disorders / Q000235:genetics / Q000523:psychology; D015161:Dementia, Multi-Infarct / Q000235:genetics / Q000523:psychology; D004200:Diseases in Twins; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D014427:Twins
D001057:Apolipoproteins E