Affiliations: [a] Neuroimaging Research, Barrow Neurological Institute, Phoenix, AZ, USA
| [b] School of Life Sciences, Arizona State University, Phoenix, AZ, USA
| [c] Mayo Clinic Arizona, Phoenix, AZ, USA
| [d] Muhammad Ali Parkinson Center at Barrow Neurological Institute, Phoenix, AZ, USA
Correspondence:
[*]
Correspondence to: Ashley M. Stokes, Barrow Neuroimaging Innovation Center, Barrow Neurological Institute / Saint Joseph’s Hospital and Medical Center, 350 West Thomas Road, Phoenix, AZ 85013, USA. Tel.: +1 602 406 8789; E-mail: ashley.stokes@barrowneuro.org.
Abstract: Background:Imaging biomarkers are increasingly used in Alzheimer’s disease (AD), and the identification of sex differences using neuroimaging may provide insight into disease heterogeneity, progression, and therapeutic targets. Objective:The purpose of this study was to investigate differences in grey matter (GM) volume and white matter (WM) microstructural disorganization between males and females with AD using voxel-based morphometry (VBM) and free-water-corrected diffusion tensor imaging (FW-DTI). Methods:Data were downloaded from the OASIS-3 database, including 158 healthy control (HC; 86 females) and 46 mild AD subjects (24 females). VBM and FW-DTI metrics (fractional anisotropy (FA), axial and radial diffusivities (AxD and RD, respectively), and FW index) were compared using effect size for the main effects of group, sex, and their interaction. Results:Significant group and sex differences were observed, with no significant interaction. Post-hoc comparisons showed that AD is associated with reduced GM volume, reduced FW-FA, and higher FW-RD/FW-index, consistent with neurodegeneration. Females in both groups exhibited higher GM volume than males, while FW-DTI metrics showed sex differences only in the AD group. Lower FW, lower FW-FA and higher FW-RD were observed in females relative to males in the AD group. Conclusion:The combination of VBM and DTI may reveal complementary sex-specific changes in GM and WM associated with AD and aging. Sex differences in GM volume were observed for both groups, while FW-DTI metrics only showed significant sex differences in the AD group, suggesting that WM tract disorganization may play a differential role in AD pathophysiology between females and males.
