Association between glymphatic system function and cognitive impairment in elderly patients with late-onset epilepsy

Recent studies have shown that late-onset epilepsy (LOE) is accompanied with cognitive decline and increased risk of dementia, particularly Alzheimer's disease (AD). However, the pathophysiological mechanism underlying the cognitive decline in LOE remains unclear. The aim of current study was to evaluate the relationship between glymphatic system (GS) function and cognitive decline in LOE patients using the diffusion tensor imaging (DTI) analysis along the perivascular space (DTI-ALPS).

Medical records and neuro-imaging data were obtained from 21 LOE patients with cognitive decline, 14 LOE patients without cognitive decline, and 20 age- and sex-matched healthy controls (HCs). Plasma biomarkers including Aβ42 and Aβ40 were examined using single-molecule array (Simoa) assays. The DTI-ALPS parameter was calculated and correlated with the clinical characteristics of LOE, including age, seizure frequency, duration of epilepsy, Mini-Mental State Examination (MMSE), and Aβ42/40. Regression models were used to evaluate the influencing factors of DTI-ALPS index.

LOE patients exhibited a decreased ALPS index and Aβ42/40 compared with the HCs. Post-hoc analysis indicated that the DTI-ALPS index and Aβ42/40 in LOE patients with cognitive decline was significantly lower in relative to LOE patients without cognitive decline and HCs. Spearman correlations showed a negative correlation between DTI-ALPS index and age, seizure frequency and disease duration while a positive correlations between the DTI-ALPS index and Aβ42/40 and MMSE scores in LOE patients. Linear regression analysis suggested that the DTI-ALPS index was independently related to age, Aβ42/40 and MMSE score after correcting for gender, education, and vascular risk factors.

Our findings using DTI-ALPS method found a positive correlation between cognitive decline and GS dysfunction in LOE patients, and may indicate a potential internal link between age-related LOEU and dementia formation. Therefore, the DTI-ALPS index may serve as a potential imaging marker for diagnosing and monitoring the GS function in LOE patients.