Amalia Peterson1,2 | Aditi Sathe1 | Dimitrios Zaras1 | Yisu Yang1 | Alaina Durant1 | Kacie D. Deters3 | Niranjana Shashikumar1 | Kimberly R. Pechman1 | Michael E. Kim4 | Chenyu Gao5 | Nazirah Mohd Khairi5 | Zhiyuan Li5 | Tianyuan Yao4 | Yuankai Huo4,5 | Logan Dumitrescu1,2,6,7 | Katherine A. Gifford1,2 | Jo Ellen Wilson1,8,9 | Francis E. Cambronero1 | Shannon L. Risacher10,11 | Lori L. Beason-Held12 | Yang An12 | Konstantinos Arfanakis13,14,15 | Guray Erus16 | Christos Davatzikos16 | Duygu Tosun17 | Arthur W. Toga18 | Paul M. Thompson19 | Elizabeth C. Mormino20 | Mohamad Habes21 | Di Wang21 | Panpan Zhang1,22 | Kurt Schilling23,24 | Alzheimer’s Disease Neuroimaging Initiative (ADNI) | The BIOCARD | Study Team | The Alzheimer’s Disease Sequencing Project (ADSP) | Marilyn Albert25 | Walter Kukull26 | Sarah A. Biber26 | Bennett A. Landman2,4,5,7,23,24,27 | Sterling C. Johnson28,29 | Julie Schneider14 | Lisa L. Barnes14 | David A. Bennett14 | Angela L. Jefferson1,2,4 | Susan M. Resnick12 | Andrew J. Saykin10,11 | Timothy J. Hohman1,2,6,7 | Derek B. Archer1,2,6,7

Correspondence

Derek B. Archer, Vanderbilt Memory and Alzheimer’s Center, 3319 West End Ave., Nashville, TN 37203, USA. Email: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

Funding information

BAL, Grant/Award Number: R01-EB017230; DBA, Grant/Award Number: K01-AG073584; TJH, Grant/Award Number: U24-AG074855; Vanderbilt Clinical Translational Science Award, Grant/Award Numbers: UL1-TR000445, UL1-TR002243; Vanderbilt’s High-Performance Computer Cluster for Biomedical Research, Grant/Award Numbers: R01-AG080821, S10-OD023680; Alzheimer’s Association, Grant/Award Number: IIRG-08-88733(ALJ); NIH, Grant/Award Numbers: K01-EB032898 (KGS), R01-EB017230 (BAL), K01-AG073584 (DBA), U24-AG074855 (TJH), R01-AG059716 (TJH), UL1-TR000445 (Vanderbilt Clinical Translational Science Award), UL1-TR002243 (Vanderbilt Clinical Translational Science Award), S10-OD02380 (Vanderbilt’s High-Performance Computer Cluster for Biomedical Research), R01-AG080821 (MH), R01-AG034962 (ALJ), R01-AG056534 (ALJ), R01-AG062826 (KAG), U19-AG03655 (MA); Intramural NIH, Grant/Award Number: 75N95D22P00141

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

© 2024 The Author(s). Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.

Abstract

INTRODUCTION: The effects of sex and apolipoprotein E (APOE)—Alzheimer’s disease (AD) risk factors—on white matter microstructure are not well characterized.

METHODS: Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)–corrected and harmonized. This dataset included 4741 participants (age = 73.06 ± 9.75) with 9671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FAFWcorr) were used to assess differences in white matter microstructure by sex and APOE ε4 carrier status.

RESULTS: Sex differences in FAFWcorr in projection tracts and APOE ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced.

DISCUSSION: There are prominent differences in white matter microstructure by sex and APOE ε4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted.

KEYWORDS

aging, Alzheimer’s disease, sex differences, white matter disease

Highlights

∙ Sex and apolipoprotein E (APOE) ε4 carrier status relate to white matter microstruc tural integrity.

∙ Females generally have lower free water–corrected fractional anisotropy compared to males.

∙ APOE ε4 carriers tended to have higher free water than non-carriers.