Sex, apolipoprotein E epsilon 4 status, and hippocampal volume in mild cognitive impairment
Fleisher A, Grundman M, Jack CR, Petersen RC, Taylor C, Kim HT, Schiller DH, Bagwell V et al.. Archives of neurology, 2005-06-01
Topic: Brain proteins, microglia and lab models
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. 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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APA 7th
Fleisher, A., Grundman, M., Jack, C. R., Petersen, R. C., Taylor, C., Kim, H. T., et al. (2005). Sex, apolipoprotein E epsilon 4 status, and hippocampal volume in mild cognitive impairment. Archives of neurology. https://doi.org/10.1001/archneur.62.6.953
Vancouver
Fleisher A, Grundman M, Jack CR, Petersen RC, Taylor C, Kim HT, et al. Sex, apolipoprotein E epsilon 4 status, and hippocampal volume in mild cognitive impairment. Archives of neurology. 2005. doi:10.1001/archneur.62.6.953. PMID: 15956166.
BibTeX
@article{fleisher2005-15956166,
author = {Fleisher, A. and Grundman, M. and Jack, C. R. and Petersen, R. C. and Taylor, C. and Kim, H. T. and Schiller, D. H. and Bagwell, V. and others},
title = {{Sex, apolipoprotein E epsilon 4 status, and hippocampal volume in mild cognitive impairment}},
journal = {Archives of neurology},
year = {2005},
doi = {10.1001/archneur.62.6.953},
pmid = {15956166},
url = {https://doi.org/10.1001/archneur.62.6.953}
}
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Key findings
- 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.
- 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.
- 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.
Why it matters
In this study of people with mild cognitive impairment, women carrying one or two APOE*E4 alleles had significantly reduced hippocampal volume, while men showed this only with two alleles. It describes a risk-related pattern and offers no treatment, cure or prevention.
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Study details
- Participants193
- Evidence strengthLow
How this study scored 50/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of neurology) |
| Journal's citation record | 3 / 4 | Archives of Neurology: journal h-index 353 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2005 — older than 20 years, still counted |
| Sample size | 2 / 4 | 193 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 260 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.3 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 3 / 6 | Cited 7.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 23 other studies in this library |
| Still being cited | 2 / 4 | Cited 25 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Adam Fleisher: h-index 93 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California San Diego: institution h-index 1,852 (OpenAlex) |
| Multicenter collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15956166) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 50 / 100 | — |
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