Sex, racial, and APOE-ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease

Amalia Peterson; Aditi Sathe; Dimitrios Zaras; Yisu Yang; Alaina Durant; Kacie D Deters; Niranjana Shashikumar; Kimberly R Pechman; Michael E Kim; Chenyu Gao; Nazirah Mohd Khairi; Zhiyuan Li; Tianyuan Yao; Yuankai Huo; Logan Dumitrescu; Katherine A Gifford; Jo Ellen Wilson; Francis Cambronero; Shannon L Risacher; Lori L Beason-Held; Yang An; Konstantinos Arfanakis; Guray Erus; Christos Davatzikos; Duygu Tosun; Arthur W Toga; Paul M Thompson; Elizabeth C Mormino; Panpan Zhang; Kurt Schilling; Alzheimer’s Disease Neuroimaging Initiative (ADNI); BIOCARD Study Team; Alzheimer’s Disease Sequencing Project (ADSP); Marilyn Albert; Walter Kukull; Sarah A Biber; Bennett A Landman; Sterling C Johnson; Julie Schneider; Lisa L Barnes; David A Bennett; Angela L Jefferson; Susan M Resnick; Andrew J Saykin; Timothy J Hohman; Derek B Archer

doi:10.1101/2024.06.10.598357

Sex, racial, and APOE-ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease

bioRxiv [Preprint]. 2024 Jun 12:2024.06.10.598357. doi: 10.1101/2024.06.10.598357.

Authors

Amalia Peterson^{1

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 Huo^{4

5}, Logan Dumitrescu^{1

2

6

7}, Katherine A Gifford^{1

2}, Jo Ellen Wilson^{1

8

9}, Francis Cambronero¹, Shannon L Risacher^{10

11}, Lori L Beason-Held¹², Yang An¹², Konstantinos Arfanakis^{13

14

15}, Guray Erus¹⁶, Christos Davatzikos¹⁶, Duygu Tosun¹⁷, Arthur W Toga¹⁸, Paul M Thompson¹⁹, Elizabeth C Mormino²⁰, Panpan Zhang^{1

21}, Kurt Schilling^{22

23}; Alzheimer’s Disease Neuroimaging Initiative (ADNI); BIOCARD Study Team; Alzheimer’s Disease Sequencing Project (ADSP); Marilyn Albert²⁴, Walter Kukull²⁵, Sarah A Biber²⁵, Bennett A Landman^{2

4

5

7

22

23

26}, Sterling C Johnson^{27

28}, Julie Schneider¹⁴, Lisa L Barnes¹⁴, David A Bennett¹⁴, Angela L Jefferson^{1

2

4}, Susan M Resnick¹², Andrew J Saykin^{10

11}, Timothy J Hohman^{1

2

6

7}, Derek B Archer^{1

2

6

7}

Affiliations

¹ Vanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, TN.
² Department of Neurology, Vanderbilt University Medical Center, Nashville, TN.
³ Department of Integrative Biology and Physiology, University of California, Los Angeles.
⁴ Department of Computer Science, Vanderbilt University, Nashville, TN.
⁵ Department of Electrical and Computer Engineering, Vanderbilt University, Nashville, TN.
⁶ Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN.
⁷ Vanderbilt Brain Institute, Vanderbilt University Medical Center, Nashville, TN.
⁸ Center for Cognitive Medicine, Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN.
⁹ Veteran's Affairs, Geriatric Research, Education and Clinical Center, Tennessee Valley Healthcare System.
¹⁰ Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN.
¹¹ Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN.
¹² Laboratory for Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD.
¹³ Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL.
¹⁴ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL.
¹⁵ Department of Diagnostic Radiology, Rush University Medical Center, Chicago, IL.
¹⁶ Department of Radiology, University of Pennsylvania, Philadelphia, PA.
¹⁷ Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA.
¹⁸ Laboratory of Neuroimaging, USC Stevens Institute of Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Los Angeles, CA.
¹⁹ Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, CA.
²⁰ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA.
²¹ Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN.
²² Department of Radiology & Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN2.
²³ Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN.
²⁴ Department of Neurology, Johns Hopkins School of Medicine Baltimore, MD.
²⁵ National Alzheimer's Coordinating Center, University of Washington, Seattle, WA.
²⁶ Department of Biomedical Engineering, Vanderbilt University, Nashville, TN.
²⁷ Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI.
²⁸ Wisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin, Madison, WI.

Abstract

Introduction: The effects of sex, race, and Apolipoprotein E (APOE) - Alzheimer's disease (AD) risk factors - on white matter integrity are not well characterized.

Methods: Diffusion MRI data from nine well-established longitudinal cohorts of aging were free-water (FW)-corrected and harmonized. This dataset included 4,702 participants (age=73.06 ± 9.75) with 9,671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FA_FWcorr) were used to assess differences in white matter microstructure by sex, race, and APOE-ε4 carrier status.

Results: Sex differences in FA_FWcorr in association and projection tracts, racial differences in FA_FWcorr 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, race, 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.

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Preprint

Abstract

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