Sex, apolipoprotein E epsilon 4 status, and hippocampal volume in mild cognitive impairment.
BACKGROUND
Subjects with mild cognitive impairment (MCI) have been shown to have reduced hippocampal volumes relative to normal elderly control subjects. The presence of the apolipoprotein E epsilon4 (APOE*E4) allele has been associated with greater hippocampal atrophy in women than in men with Alzheimer disease. This relationship has not been demonstrated in MCI.


OBJECTIVE
To examine the relationship between APOE genotype and hippocampal volume in men and women with MCI.


METHODS
This study evaluated MCI in 193 subjects (86 women and 107 men) participating in a multicenter clinical trial, all of whom underwent magnetic resonance imaging at their baseline visit. We evaluated the association among the number of APOE*E4 alleles, memory performance, and hippocampal volume in men and women with tests of means and multiple linear regressions.


RESULTS
Compared with MCI subjects with no APOE*E4 alleles, women with 1 or 2 APOE*E4 alleles were found to have significantly reduced hippocampal volume, whereas men only showed a significant reduction in hippocampal volume when carrying 2 APOE*E4 alleles. Worsening of performance on a delayed word recall task (Alzheimer's Disease Assessment Scale cognitive subscale) showed an identical pattern in association with APOE*E4 allele dose and sex. Furthermore, when controlling for memory performance on delayed word recall, the APOE*E4 effect on hippocampal volumes was attenuated in men, but remained significant in women.


CONCLUSIONS
The APOE*E4 genotype status appears to have a greater deleterious effect on gross hippocampal pathology and memory performance in women than in men.
Fleisher
Adam
A
Department of Neurosciences, University of California-San Diego, La Jolla, Calif, USA. afleisher@ucsd.edu
Grundman
Michael
M
Jack
Clifford R
CR
Petersen
Ronald C
RC
Taylor
Curtis
C
Kim
Hyun T
HT
Schiller
Denise H B
DH
Bagwell
Victor
V
Sencakova
Drahomira
D
Weiner
Myron F
MF
DeCarli
Charles
C
DeKosky
Steven T
ST
van Dyck
Christopher H
CH
Thal
Leon J
LJ
D000368:Aged; D000483:Alleles; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001284:Atrophy; D003072:Cognition Disorders / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D012727:Sex Characteristics
D053327:Apolipoprotein E4; D001057:Apolipoproteins E