Cognitive function changes and DTI-ALPS index in postmenopausal women

Background Cognitive decline in postmenopausal women is a growing public health concern, with estrogen deficiency linked to brain aging. However, the role of the brain's lymphatic-like system—assessed via the diffusion tensor imaging along the perivascular space (DTI-ALPS) index—in mediating estrogen-cognitive associations remains unclear. This study investigated whether the DTI-ALPS index mediates the relationship between estrogen levels and cognitive function in postmenopausal women. Methods Data from 55 women recruited from outpatient clinics were analyzed. A combination of traditional and advanced statistical methods was used. These included MANOVA, non-linear correlation analysis, structural equation modeling, and machine learning algorithms. Results Postmenopausal women exhibited lower right and mean ALPS indices ( P < 0.05) and worse cognitive performance on reaction time tasks ( P < 0.05). The mean ALPS index fully mediated the relationship between estrogen and cognitive accuracy (e.g., Stroop: r = 0.588, P < 0.01), with machine learning ranking ALPS index and estrogen as top predictors of cognitive function. Conclusions Reduced brain lymphatic function (lower ALPS index) is associated with cognitive decline in postmenopausal women, and this relationship is mediated by estrogen levels. The DTI-ALPS index may serve as a novel biomarker for menopause-related cognitive health.