Sex differences in white matter amplitude of low-frequency fluctuation associated with cognitive performance across the Alzheimer's disease continuum.

Journal: Journal of Alzheimer's disease : JAD
Published Date: Aug 5, 2025

Abstract

BackgroundSex differences in Alzheimer's disease (AD) progression offer insights into pathogenesis and clinical management. White matter (WM) amplitude of low-frequency fluctuation (ALFF), reflecting neural activity, represents a potential disease biomarker.ObjectiveTo explore whether there are sex differences in regional WM ALFF among AD patients, amnestic mild cognitive impairment (aMCI) patients, and healthy controls (HCs), how it is related to cognitive performance, and whether it can be used for disease classification.MethodsResting-state functional magnetic resonance images and cognitive assessments were obtained from 85 AD (36 female), 52 aMCI (23 female), and 78 HCs (43 female). Two-way ANOVA examined group × sex interactions for regional WM ALFF and cognitive scores. WM ALFF-cognition correlations and support vector machine diagnostic accuracy were evaluated.ResultsSex × group interaction effects on WM ALFF were detected in the right superior longitudinal fasciculus ( = 20.08,  < 0.001), left superior longitudinal fasciculus ( = 5.45,  < 0.001) and right inferior longitudinal fasciculus ( = 6.00,  = 0.001). These WM ALFF values positively correlated with different cognitive performance between sexes. The support vector machine learning best differentiated aMCI from AD in the full cohort and males (accuracy = 75%), and HCs from aMCI in females (accuracy = 93%).ConclusionsSex differences in regional WM ALFF during AD progression are associated with cognitive performance and can be utilized for disease classification.

Authors

  • Xiao Chen
  • Shanshan Zhou
    From the Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Rd, Chaoyang District, Beijing 100029, China (Z.Z., Y.G., N.Z., H.W., R.W., L.X.); School of Biomedical Engineering, Sun Yat-Sen University, Guangzhou, China (W.Z., Z.G., H.Z.); Keya Medical Company, Shenzhen, China (X.H.); Department of Cardiology, Chinese PLA General Hospital, Beijing, China (S.Z.); Department of Radiology, The First Hospital of China Medical University, Shenyang, China (X.D.); Cardiovascular Research Centre, Royal Brompton Hospital, London, UK (G.Y.); National Heart and Lung Institute, Imperial College London, London, UK (G.Y.); and Department of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, Calif (K.N.).
  • Wenrui Wang
    School of Electronic Engineering, Beijing University of Posts and Telecommunications, Beijing 100876, China.
  • Ziwen Gao
    Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
  • Wei Ye
    AliveX Biotech, Shanghai, China.
  • Wanqiu Zhu
    Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
  • Yun Lu
    Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou Province, China.
  • Ju Ma
    Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
  • Xiaohu Li
    Department of Radiology, The First Affiliated Hospital of Anhui Medical University, 230022, Hefei, Anhui, China.
  • Yongqiang Yu
    College of Electronic Engineering, National University of Defense Technology, Hefei 230037, China.
  • Xiaoshu Li
    Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

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