Sex, apolipoprotein E ε4 status, and hippocampal volume in mild cognitive impairment

Adam Fleisher, Michael Grundman, Clifford R. Jack, Ronald C. Petersen, Curtis Taylor, Hyun T. Kim, Denise H B Schiller, Victor Bagwell, Drahomira Sencakova, Myron F. Weiner, Charles DeCarli, Steven T. DeKosky, Christopher H. Van Dyck, Leon J. Thal

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Abstract

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 ε4 (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. Design: 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. Conclusion: The APOE*E4 genotype status appears to have a greater deleterious effect on gross hippocampal pathology and memory performance in women than in men.

Original languageEnglish (US)
Pages (from-to)953-957
Number of pages5
JournalArchives of Neurology
Volume62
Issue number6
DOIs
StatePublished - Jun 2005

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Apolipoprotein E4
Alleles
Alzheimer Disease
Genotype
Cognitive Dysfunction
Mild Cognitive Impairment
Allele
Multicenter Studies
Atrophy
Linear Models
Magnetic Resonance Imaging
Clinical Trials
Pathology

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Fleisher, A., Grundman, M., Jack, C. R., Petersen, R. C., Taylor, C., Kim, H. T., ... Thal, L. J. (2005). Sex, apolipoprotein E ε4 status, and hippocampal volume in mild cognitive impairment. Archives of Neurology, 62(6), 953-957. https://doi.org/10.1001/archneur.62.6.953

Sex, apolipoprotein E ε4 status, and hippocampal volume in mild cognitive impairment. / Fleisher, Adam; Grundman, Michael; Jack, Clifford R.; Petersen, Ronald C.; Taylor, Curtis; Kim, Hyun T.; Schiller, Denise H B; Bagwell, Victor; Sencakova, Drahomira; Weiner, Myron F.; DeCarli, Charles; DeKosky, Steven T.; Van Dyck, Christopher H.; Thal, Leon J.

In: Archives of Neurology, Vol. 62, No. 6, 06.2005, p. 953-957.

Research output: Contribution to journalArticle

Fleisher, A, Grundman, M, Jack, CR, Petersen, RC, Taylor, C, Kim, HT, Schiller, DHB, Bagwell, V, Sencakova, D, Weiner, MF, DeCarli, C, DeKosky, ST, Van Dyck, CH & Thal, LJ 2005, 'Sex, apolipoprotein E ε4 status, and hippocampal volume in mild cognitive impairment', Archives of Neurology, vol. 62, no. 6, pp. 953-957. https://doi.org/10.1001/archneur.62.6.953
Fleisher A, Grundman M, Jack CR, Petersen RC, Taylor C, Kim HT et al. Sex, apolipoprotein E ε4 status, and hippocampal volume in mild cognitive impairment. Archives of Neurology. 2005 Jun;62(6):953-957. https://doi.org/10.1001/archneur.62.6.953
Fleisher, Adam ; Grundman, Michael ; Jack, Clifford R. ; Petersen, Ronald C. ; Taylor, Curtis ; Kim, Hyun T. ; Schiller, Denise H B ; Bagwell, Victor ; Sencakova, Drahomira ; Weiner, Myron F. ; DeCarli, Charles ; DeKosky, Steven T. ; Van Dyck, Christopher H. ; Thal, Leon J. / Sex, apolipoprotein E ε4 status, and hippocampal volume in mild cognitive impairment. In: Archives of Neurology. 2005 ; Vol. 62, No. 6. pp. 953-957.
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abstract = "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 ε4 (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. Design: 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. Conclusion: The APOE*E4 genotype status appears to have a greater deleterious effect on gross hippocampal pathology and memory performance in women than in men.",
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