DTI-ALPS index and cognitive performance in temporal lobe epilepsy with and without hippocampal sclerosis: A cross-sectional study.

BACKGROUND

Temporal lobe epilepsy (TLE) often involves cognitive impairment, with hippocampal sclerosis (HS) as a key pathology. Although neuronal loss and proteinopathy are established mechanisms, the role of perivascular clearance pathways remains underexplored in TLE.

OBJECTIVE

This retrospective, single-centre cross-sectional study included 212 participants aged 24-71 years: 79 patients with TLE and visually identified unilateral hippocampal sclerosis, 57 patients with TLE without hippocampal sclerosis, and 76 healthy controls. We aimed to compare the DTI‑ALPS index-an indirect diffusion‑derived index that may be associated with perivascular‑related processes-and its association with cognition in TLE with and without HS.

RESULTS

After adjusting for age, sex, and education, the global ALPS index was significantly lower in TLE‑HS than in TLE‑non‑HS and HC (both p < 0.05), and also lower in TLE‑non‑HS than in HC ( p < 0.01). For right‑hemispheric ALPS, both patient groups were lower than HC ( p < 0.01), but TLE‑HS and TLE‑non‑HS did not differ significantly ( p = 0.12). Left‑hemispheric ALPS was lower in TLE‑HS than in the other two groups ( p < 0.05), whereas TLE‑non‑HS and HC did not differ (p = 0.08). Cognitive performance showed that TLE‑HS performed worse than both other groups on all measures (all p < 0.05); TLE‑non‑HS performed worse than HC on MoCA, AVLT, SDMT and SCWT ( p < 0.05) but not on TMT(B‑A) ( p = 0.08). Within‑group partial correlations with FDR correction (q < 0.05) revealed significant associations between the ALPS index and MoCA, SDMT, and TMT(B‑A) in the TLE‑HS group; with SCWT in the TLE‑non‑HS group; and with SDMT in the HC group.

CONCLUSIONS

The DTI‑ALPS index was lower in patients with TLE, particularly those with visually classified HS, and was associated with selected cognitive measures in a group‑specific manner. No formal statistical comparison of correlation strength across groups was performed. Because DTI‑ALPS is an indirect diffusion‑derived index and the study was cross‑sectional, these findings do not establish causality or a biological mechanism. Further longitudinal studies using direct measures of cerebrospinal fluid dynamics are required.