Accelerated hippocampal atrophy in APOE ε4 homozygotes and females: Longitudinal findings from the Tohoku Medical Megabank MRI study.

Authors

Shunji Mugikura, Naoko Mori, Megumi Satake, Ippei Chiba, Makiko Taira, Takuya Koyama, Tomomi Onuma, Tomo Saito, Masato Takase, Ikuko N Motoike, Takanori Hidaka, Akihito Otsuki, Masatsugu Orui, Taku Obara, Fuji Nagami, Naoki Nakaya, Soichi Ogishima, Kazuki Kumada, Fumiki Katsuoka, Seizo Koshiba, Yasuyuki Taki, Ritsuko Shimizu, Shinichi Kuriyama, Kinuko Ohneda, Yoko Izumi, Nobuo Fuse, Atsushi Hozawa, Kengo Kinoshita, Masayuki Yamamoto

Published in

Neuroradiology. Oct 09, 2026. Epub Oct 09, 2026.

Abstract

The apolipoprotein E ε4 allele is a major genetic risk factor for Alzheimer's disease, but its longitudinal effect on hippocampal atrophy is unclear. Selective hippocampal atrophy, defined as greater hippocampal volume (HpV) loss relative to total brain volume (TBV), is an early marker of preclinical Alzheimer's disease. We examined age-related effects of APOE ε4 on longitudinal hippocampal atrophy in a large population-based cohort.
We analyzed MRI data from 9,453 adults in the Tohoku Medical Megabank MRI Study, including 5,774 participants with follow-up MRI after a mean interval of 4.7 years. Cross-sectional analyses used linear regression to assess HpV and TBV, adjusting for age, sex, APOE genotype, and intracranial volume. Longitudinal analyses assessed HpV-Ratio and TBV-Ratio, defined as the second MRI volume divided by the first volume, using regression models including age, sex, APOE genotype, MRI interval, and interaction terms between age and APOE genotype and between age and sex. Montreal Cognitive Assessment (MoCA) scores obtained at the second MRI were included to assess effects independent of cognition.
No significant APOE genotype effects were observed in cross-sectional analyses. Longitudinally, ε4/ε4 carriers showed greater decline in HpV-Ratio than ε3/ε3 and ε3/ε4 carriers, and females showed lower HpV-Ratio than males. No APOE genotype or sex main effects were observed for TBV-Ratio. Interactions between age and APOE genotype and between age and sex demonstrated age-related acceleration of HpV-Ratio decline in ε4/ε4 carriers and females, and these effects persisted after adjustment for MoCA scores.
APOE ε4 homozygosity and female sex accelerate selective hippocampal atrophy in population-based cohorts.

PMID:
42853241
Bibliographic data and abstract were imported from PubMed on 09 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.