Glymphatic System Dysfunction in Elderly Patients with Late-Onset Epilepsy and Comorbid Chronic Insomnia Revealed by Diffusion Tensor Imaging Along the Perivascular Space (DTI-ALPS)

Abstract

Purpose: This study assessed the influence of glymphatic system (GS) dysfunction on cognitive decline in patients with late-onset epilepsy (LOE) and comorbid chronic insomnia utilizing diffusion tensor imaging along the perivascular space (DTI-ALPS).

Methods: Clinical data were collected from 42 elderly LOE patients, 17 with and 25 without chronic insomnia, as well as from 22 healthy controls (HCs) matched for age and sex. Simoa assays were performed to quantify Aβ42 and Aβ40 as plasma biomarkers of age-related neuropathology, and associations between the DTI-ALPS index and age, seizure frequency and duration, Sleep Quality Index (PSQI), Hamilton Rating Scale for Depression (HAMD), Hamilton Rating Scale for Anxiety (HAMA), Mini-Mental State Examination (MMSE), and Aβ42:Aβ40 ratio (Aβ42/40) were assessed using Spearman correlation tests and multivariate logistic regression models.

Results: Both DTI-ALPS index and Aβ42/40 were significantly lower among LOE patients compared to HCs, and post-hoc analysis revealed even lower Aβ42/40 and DTI-ALPS index values among LOE patients with comorbid chronic insomnia compared to HCs and LOE patients without chronic insomnia. The DTI-ALPS index was negatively correlated with age, disease duration, PSQI score, and HAMA score, and positively correlated with Aβ42/40 and MMSE score among LOE patients according to Spearman's tests. Multivariate linear regression revealed independent associations of the DTI-ALPS index with age, MMSE score, Aβ42/40, and PSQI after adjusting for vascular risk factors, sex, and education.

Conclusion: These results suggest that the GS is dysfunctional in LOE and may exacerbate sleep disruption and cognitive impairments.

Keywords: DTI-ALPS; chronic insomnia; cognitive function; glymphatic system; late-onset epilepsy.

Figure 1

The process for obtaining DTI analysis along the perivascular space index. (A) Place the region of interests in the areas with projection and association fibers. (B) The direction of the paravascular space (gray columns) and the orientation of the three neural fiber tracts. (C) The directions of the projection fiber tracts (blue; z-axis), association fibers tracts (green, Y-axis), and subcortical fibers tracts (red, X-axis). (D) Flowchart illustrating the process of calculating DTI-ALPS index.

Figure 2

Linear correlation between DTI-Alps index and clinical indicators. (A) Negative correlation between the DTI-ALPS index and ages in all participants. (B) Positive correlation between the DTI-ALPS index and Aβ42/40 in LOE patients. (C) Positive correlation between DTI-ALPS index and MMSE scores in LOE patients. (D) Negative correlation between DTI-ALPS index and seizure duration in LOE patients. (E) Negative correlation between the DTI-ALPS index and HAMA scores. (F) Negative correlation between the DTI-ALPS index and PSQI scores.