Sex differences in white matter microstructure in aging and Alzheimer’s disease: A multi‐site free‐water imaging study

Medientyp: E-Artikel
Titel: Sex differences in white matter microstructure in aging and Alzheimer’s disease: A multi‐site free‐water imaging study
Beteiligte: Archer, Derek B; Shashikumar, Niranjana; Jasodanand, Varuna; Moore, Elizabeth E.; Pechman, Kimberly R.; Bilgel, Murat; Beason‐Held, Lori L; An, Yang; Shafer, Andrea T; Risacher, Shannon L.; Landman, Bennett A.; Jefferson, Angela L.; Saykin, Andrew J.; Resnick, Susan M.; Hohman, Timothy J.
Erschienen: Wiley, 2022
Erschienen in: Alzheimer's & Dementia
Sprache: Englisch
DOI: 10.1002/alz.066752
ISSN: 1552-5260; 1552-5279
Schlagwörter: Psychiatry and Mental health ; Cellular and Molecular Neuroscience ; Geriatrics and Gerontology ; Neurology (clinical) ; Developmental Neuroscience ; Health Policy ; Epidemiology
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Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Sex differences in gray matter alterations in aging and AD have been reported, but there have been few large‐scale studies evaluating white matter microstructure. The goal of this study is to leverage multi‐site harmonized diffusion MRI data in tandem with free‐water (FW) imaging to determine the association between sex and white matter microstructure in aging and AD.</jats:p></jats:sec><jats:sec><jats:title>Method</jats:title><jats:p>The dataset used in this study leveraged cross‐sectional data from several cohorts of aging [Alzheimer’s Neuroimaging Initiative (ADNI), Baltimore Longitudinal Study of Aging (BLSA), Vanderbilt Memory & Aging Project (VMAP)]. This dataset included 1,898 participants (72±9 years, 59% female). Data was processed using standard preprocessing techniques and followed up with FW postprocessing. FW and FW‐corrected intracellular metrics of fractional anisotropy (FA<jats:sub>T</jats:sub>), radial diffusivity (RD<jats:sub>T</jats:sub>), and axial diffusivity (AD<jats:sub>T</jats:sub>) were then quantified within seven white matter tractography templates (see <jats:bold>Figure 1A</jats:bold>) and harmonized using the ComBat technique. The sex differences for each microstructural metric were then determined using a linear regression model covarying for age, diagnosis, education, and <jats:italic>APOE</jats:italic>‐ε4 carrier status. Secondary analyses were conducted to determine <jats:italic>sex x diagnosis</jats:italic> interactions on white matter microstructure.</jats:p></jats:sec><jats:sec><jats:title>Result</jats:title><jats:p>While we found no sex differences in FW, there were significant associations in all intracellular metrics. Females had significantly lower FA<jats:sub>T</jats:sub> in the association (p<jats:sub>FDR</jats:sub>=6.62x10<jats:sup>‐10</jats:sup>), limbic (p<jats:sub>FDR</jats:sub>=5.28x10<jats:sup>‐9</jats:sup>), motor transcallosal (TC) (p<jats:sub>FDR</jats:sub>=0.008), prefrontal TC (p<jats:sub>FDR</jats:sub>=6.34x10<jats:sup>‐6</jats:sup>), and projection (p<jats:sub>FDR</jats:sub>=4.74x10<jats:sup>‐20</jats:sup>) tracts and significantly lower AD<jats:sub>T</jats:sub> in the association (p<jats:sub>FDR</jats:sub>=5.23x10<jats:sup>‐10</jats:sup>), limbic (p<jats:sub>FDR</jats:sub>=1.84x10<jats:sup>‐6</jats:sup>), prefrontal TC (p<jats:sub>FDR</jats:sub>=4.41x10<jats:sup>‐11</jats:sup>), and projection (p<jats:sub>FDR</jats:sub>=5.29x10<jats:sup>‐17</jats:sup>) tracts. For RD<jats:sub>T</jats:sub>, females exhibited higher RD<jats:sub>T</jats:sub> in all tracts (p<jats:sub>FDR</jats:sub> range: 4.94x10<jats:sup>‐16</jats:sup> – 0.022). Illustrations of these results can be found in <jats:bold>Figure 1</jats:bold>. Sex differences were compared across cohorts and were similar (<jats:bold>Figure 2</jats:bold>). The only significant <jats:italic>sex x diagnosis</jats:italic> interaction was for the projection tract RD<jats:sub>T</jats:sub> measure (p<jats:sub>FDR</jats:sub>=0.043, <jats:bold>Figure 3</jats:bold>).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>This study suggests intracellular microstructural values (i.e., FA<jats:sub>T</jats:sub>, AD<jats:sub>T</jats:sub>, RD<jats:sub>T</jats:sub>) exhibit strong sex differences, whereby females have lower FA<jats:sub>T</jats:sub>/AD<jats:sub>T</jats:sub> and higher RD<jats:sub>T</jats:sub> compared to males. We also found a <jats:italic>sex x diagnosis</jats:italic> interaction for projection tract RD<jats:sub>T</jats:sub>, whereby females with AD exhibited lower RD<jats:sub>T</jats:sub>, but larger studies with more AD cases would be needed to further explore this finding.</jats:p></jats:sec>

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