# Cognitive function changes and DTI-ALPS index in postmenopausal women

**Authors:** Ningning Liu, Yue Zhang, Weiqing Fu, Huijun Liu

PMC · DOI: 10.3389/fnagi.2025.1593366 · Frontiers in Aging Neuroscience · 2025-06-24

## TL;DR

This study explores how estrogen levels and brain lymphatic function relate to cognitive changes in postmenopausal women.

## Contribution

The study introduces the DTI-ALPS index as a potential biomarker for menopause-related cognitive decline.

## Key findings

- Postmenopausal women had lower ALPS indices and worse cognitive performance.
- The mean ALPS index fully mediated the relationship between estrogen and cognitive accuracy.
- Machine learning identified ALPS index and estrogen as top predictors of cognitive function.

## Abstract

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.

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.

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.

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.

## Full-text entities

- **Diseases:** estrogen (MESH:D056828), Cognitive decline (MESH:D003072), ALPS (MESH:D056735)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12235314/full.md

## References

20 references — full list in the complete paper: https://tomesphere.com/paper/PMC12235314/full.md

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Source: https://tomesphere.com/paper/PMC12235314