Observational study identifies sex differences in white matter fluctuations associated with cognitive performance in Alzheimer’s disease, suggesting implications for disease classification.
Background Sex 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. Objective To 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. Methods Resting-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. Results Sex × group interaction effects on WM ALFF were detected in the right superior longitudinal fasciculus ( F = 20.08, p FDR_corrected < 0.001), left superior longitudinal fasciculus ( F = 5.45, p GRF_corrected < 0.001) and right inferior longitudinal fasciculus ( F = 6.00, p GRF_corrected = 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%). Conclusions Sex differences in regional WM ALFF during AD progression are associated with cognitive performance and can be utilized for disease classification.
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Chen et al. (2025) studied this question.
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