Research Article

Hippocampal Subfield Volume Alterations in Alzheimer’s Disease: A Sex-Stratified MRI Study in Older Adults

Volume: 52 February 20, 2026
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Hippocampal Subfield Volume Alterations in Alzheimer’s Disease: A Sex-Stratified MRI Study in Older Adults

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder in which hippocampal atrophy represents one of the earliest and most prominent structural alterations. Subfield-level morphometric analysis may therefore provide a more detailed characterization of hippocampal involvement in AD. The aim of this study was to characterize hippocampal and hippocampal subfield volume differences between individuals with AD and cognitively healthy older adults, including hemispheric asymmetry and sex-specific patterns, using automated subfield segmentation. In this cross-sectional neuroimaging study, hippocampal and hippocampal subfield volumes were examined in individuals with AD and cognitively healthy controls (HC) using structural MRI data from the OASIS-1 dataset. The analytic sample consisted of 200 participants aged 60 years and older (100 AD, 100 HC). Automated segmentation of the hippocampus and its subfields (CA1, CA2–CA3, CA4–dentate gyrus, subiculum, and SR–SL–SM) was performed using the HIPS module of the volBrain platform. Compared with HC, individuals with AD showed significant reductions in total hippocampal volume and in multiple hippocampal subfields, with medium to large effect sizes. In contrast, hippocampal asymmetry indices did not demonstrate consistent group-level differences after correction for multiple comparisons. Sex-stratified analyses revealed similar patterns of hippocampal and subfield volume reductions in female and male participants with AD. These findings indicate that AD is associated with widespread, anatomically specific hippocampal subfield volume reductions beyond global hippocampal atrophy and evident after adjustment for key confounders. Subfield-level morphometry provides a refined group-level description of hippocampal involvement in AD, although longitudinal studies are required to clarify its clinical relevance.

Keywords

Ethical Statement

This study was conducted in accordance with the ethical principles of the Declaration of Helsinki. Ethical approval was obtained from the Research Ethics Committee of Kafkas University (Decision Date and Number: 30.04.2025 – 2025/04/08). The study was performed using fully anonymized and publicly available neuroimaging data; therefore, no additional informed consent was required from participants.

Thanks

The author would like to express sincere gratitude to Hüseyin Biçeroğlu, Professor of Neurosurgery at Ege University, for his valuable scientific perspective, continuous encouragement, and thoughtful insights, which greatly contributed to the conceptual refinement of this work. His dedication to neurosurgical science and openness to interdisciplinary dialogue have been a lasting source of inspiration. The author also wishes to acknowledge a deeply personal source of motivation behind this study: her grandmother, who lived with Alzheimer’s disease for nearly a decade. Her long and dignified journey with the disease provided a profound human context to the scientific questions addressed in this work and served as a constant reminder that behind every dataset lies a lived experience. This study is dedicated to her memory and to all individuals and families affected by Alzheimer’s disease.

References

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Details

Primary Language

English

Subjects

Anatomy

Journal Section

Research Article

Publication Date

February 20, 2026

Submission Date

January 16, 2026

Acceptance Date

February 12, 2026

Published in Issue

Year 2026 Volume: 52

APA
Karakaş, A. B., & Akbulut, Y. (2026). Hippocampal Subfield Volume Alterations in Alzheimer’s Disease: A Sex-Stratified MRI Study in Older Adults. Journal of Uludağ University Medical Faculty, 52, 1865368-1865368. https://doi.org/10.32708/uutfd.1865368
AMA
1.Karakaş AB, Akbulut Y. Hippocampal Subfield Volume Alterations in Alzheimer’s Disease: A Sex-Stratified MRI Study in Older Adults. Journal of Uludağ University Medical Faculty. 2026;52:1865368-1865368. doi:10.32708/uutfd.1865368
Chicago
Karakaş, Aslı Beril, and Yalçın Akbulut. 2026. “Hippocampal Subfield Volume Alterations in Alzheimer’s Disease: A Sex-Stratified MRI Study in Older Adults”. Journal of Uludağ University Medical Faculty 52 (February): 1865368-68. https://doi.org/10.32708/uutfd.1865368.
EndNote
Karakaş AB, Akbulut Y (February 1, 2026) Hippocampal Subfield Volume Alterations in Alzheimer’s Disease: A Sex-Stratified MRI Study in Older Adults. Journal of Uludağ University Medical Faculty 52 1865368–1865368.
IEEE
[1]A. B. Karakaş and Y. Akbulut, “Hippocampal Subfield Volume Alterations in Alzheimer’s Disease: A Sex-Stratified MRI Study in Older Adults”, Journal of Uludağ University Medical Faculty, vol. 52, pp. 1865368–1865368, Feb. 2026, doi: 10.32708/uutfd.1865368.
ISNAD
Karakaş, Aslı Beril - Akbulut, Yalçın. “Hippocampal Subfield Volume Alterations in Alzheimer’s Disease: A Sex-Stratified MRI Study in Older Adults”. Journal of Uludağ University Medical Faculty 52 (February 1, 2026): 1865368-1865368. https://doi.org/10.32708/uutfd.1865368.
JAMA
1.Karakaş AB, Akbulut Y. Hippocampal Subfield Volume Alterations in Alzheimer’s Disease: A Sex-Stratified MRI Study in Older Adults. Journal of Uludağ University Medical Faculty. 2026;52:1865368–1865368.
MLA
Karakaş, Aslı Beril, and Yalçın Akbulut. “Hippocampal Subfield Volume Alterations in Alzheimer’s Disease: A Sex-Stratified MRI Study in Older Adults”. Journal of Uludağ University Medical Faculty, vol. 52, Feb. 2026, pp. 1865368-, doi:10.32708/uutfd.1865368.
Vancouver
1.Aslı Beril Karakaş, Yalçın Akbulut. Hippocampal Subfield Volume Alterations in Alzheimer’s Disease: A Sex-Stratified MRI Study in Older Adults. Journal of Uludağ University Medical Faculty. 2026 Feb. 1;52:1865368-. doi:10.32708/uutfd.1865368

ISSN: 1300-414X, e-ISSN: 2645-9027

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Journal of Uludag University Medical Faculty is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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