Association between glymphatic dysfunction and neurocognitive decline in patients with frontal lobe epilepsy

Background: The glymphatic system is essential for the maintenance of brain homeostasis. It may be impaired in patients with epilepsy, but its association with neurocognitive function remains unknown. In this study, we aimed to elucidate the association between changes in the glymphatic system and neurocognitive function in individuals diagnosed with frontal lobe epilepsy (FLE). Methods: This retrospective case-control research engaged a group of patients with FLE and age-, sex-, and education-matched healthy volunteers. All participants were subjected to extensive neurocognitive assessments, complemented by structural and diffusion-weighted imaging. The "diffusion tensor imaging analysis along the perivascular space" (DTI-ALPS) index was computed to ascertain differences in glymphatic system function between the groups. Univariate and multivariate analyses were conducted to explore associations between DTI-ALPS, clinical characteristics in patients with FLE, and the neurocognitive test outcomes for both groups. Results: Twenty-five patients mean age ± standard deviation (SD): 26.28±8.12 years, 10 females with FLE and 22 healthy control (HC) participants (average age ± SD: 25.86±6.15 years, 11 females) were included. The average ALPS-index in FLE group was significantly lower than that in HC group (1.387±0.127 vs. 1.468±0.114, P=0.026). Further, significant neurocognitive difference was noted in Trail Making Test (TMT), Stroop Color and Word Test (SCWT), Digit Span Test (DST) and similarity test (ST) between the two groups. ALPS-index scores exhibited a negative correlation with disease duration in patients with FLE (r=−0.415, P=0.039), and positive correlations with the Forward Digit Span Test (FDST, r=0.399, P=0.005) and Similarity Test (ST, r=0.395, P=0.006) in both groups. After adjusting for potential confounders, DTI-ALPS maintained a significant independent association with FDST and ST. Conclusions: The findings of the current study suggest a possible association between impairment in glymphatic function and FLE. Furthermore, results indicate that glymphatic dysfunction, as assessed via DTI-ALPS index, appears to be related to neurocognitive decline in FLE.