Glymphatic system

Perivascular space

ALPS index

Diffusion weighted images The glymphatic system is responsible for clearing waste products and protein deposits from the brain, and its dysfunction—particularly within perivascular spaces (PVS)—has been implicated in the development of Alzheimer’s disease. This study aimed to investigate alterations in PVS characteristics and diffusion metrics in healthy individuals, patients with Alzheimer’s disease, and those with mild cognitive impairment.

Three datasets were analyzed: ADNI2, the Human Connectome Project (HCP), and ADNI4, including diffusion-weighted, T1-weighted, and T2-weighted images. Diffusion metrics were derived from ADNI2, while PVS mapping was performed across datasets. Because of differences in structural image resolution, preprocessing included normalization and bias field correction. Enhanced contrast was generated for HCP and ADNI4 images. Perivascular spaces within white matter were automatically segmented using the Frangi filter, and quantitative metrics were evaluated through statistical analyses and predictive modeling.

In ADNI2, patients with Alzheimer’s disease demonstrated a lower ALPS index than healthy controls (1.16 vs. 1.31). The mean PVS count was also significantly reduced in the Alzheimer’s group (84.60 vs. 112.20). In HCP, enhanced contrast improved PVS detectability, as supported by expert visual assessment. Partial correlations between automated and visual counts reached 0.75 for enhanced contrast and 0.44 for T2-weighted images. In ADNI4, although group differences did not reach statistical significance, PVS measures—including count, volume, and volume fraction—showed a trend toward lower values in Alzheimer’s patients. Enhanced contrast further facilitated PVS visualization and quantification.

Overall, diffusion-derived indices together with clinical variables contributed to detecting Alzheimer’s-related alterations. Given the limited sample size and image resolution, further investigations using larger and more homogeneous datasets are warranted.