Reconsideration of the DTI-ALPS index as a glymphatic surrogate: disease-specific findings in small vessel disease due to cerebral amyloid angiopathy or arteriolosclerosis.

OBJECTIVES

To explore the disease-specific performance of diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index in cerebral amyloid angiopathy (CAA) and arteriolosclerosis CSVD (aCSVD).

METHODS

We retrospectively enrolled probable CAA or aCSVD patients who underwent 5.0T MRI. Disease-specific DTI-ALPS characteristics and the correlations with clinical, imaging markers, and cognition were evaluated. Regression models were applied according to outcome distributions. Multiple comparisons were controlled using the Benjamini-Hochberg false discovery rate (FDR) procedure.

RESULTS

A total of 134 participants (56 probable CAA and 78 arteriolosclerosis, mean age 64.9 ± 10.0 years, 64.9% males) were enrolled. DTI-ALPS index was significantly lower in aCSVD than in CAA (p < 0.001). After adjustment for age and sex and FDR correction, no clinical factors remained significantly associated with DTI-ALPS index. In aCSVD, DTI-ALPS was significantly associated with cognitive performance, whereas these associations did not reach statistical significance in CAA. Across both groups, DTI-ALPS was significantly associated with white matter hyperintensity volume, skeletonized fractional anisotropy, skeletonized mean diffusivity, and peak width of skeletonized mean diffusivity (all FDR-adjusted p < 0.05). Associations with PVS burden and established CAA imaging markers did not reach statistical significance.

CONCLUSION

DTI-ALPS index is heterogenous across distinct angiopathies but consistently associated with white matter microstructural damage. These subtype-specific findings question the relevance of DTI-ALPS index and caution against using DTI-ALPS index as a universal glymphatic surrogate.