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

IF 2.8 3区医学 Q2 CLINICAL NEUROLOGY

Neuroradiology Pub Date : 2026-10-09 DOI:10.1007/s00234-026-04210-6

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

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引用次数: 0

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: APOE ε4 homozygosity and female sex accelerate selective hippocampal atrophy in population-based cohorts.

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APOE ε4纯合子和女性的海马加速萎缩：来自东北医学大库MRI研究的纵向发现。

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来源期刊

Neuroradiology 医学-核医学

CiteScore

5.30

自引率

3.60%

发文量

214

审稿时长

4-8 weeks

期刊介绍： Neuroradiology aims to provide state-of-the-art medical and scientific information in the fields of Neuroradiology, Neurosciences, Neurology, Psychiatry, Neurosurgery, and related medical specialities. Neuroradiology as the official Journal of the European Society of Neuroradiology receives submissions from all parts of the world and publishes peer-reviewed original research, comprehensive reviews, educational papers, opinion papers, and short reports on exceptional clinical observations and new technical developments in the field of Neuroimaging and Neurointervention. The journal has subsections for Diagnostic and Interventional Neuroradiology, Advanced Neuroimaging, Paediatric Neuroradiology, Head-Neck-ENT Radiology, Spine Neuroradiology, and for submissions from Japan. Neuroradiology aims to provide new knowledge about and insights into the function and pathology of the human nervous system that may help to better diagnose and treat nervous system diseases. Neuroradiology is a member of the Committee on Publication Ethics (COPE) and follows the COPE core practices. Neuroradiology prefers articles that are free of bias, self-critical regarding limitations, transparent and clear in describing study participants, methods, and statistics, and short in presenting results. Before peer-review all submissions are automatically checked by iThenticate to assess for potential overlap in prior publication.