# Cognitive Decline in Nasopharyngeal Carcinoma Survivors with Post-Radiation Epilepsy: A Prospective Cohort Study

## TL;DR

NPC survivors with epilepsy experience faster cognitive decline than those without, highlighting the importance of early seizure control.

## Contribution

This study identifies a faster rate of cognitive decline in NPC survivors with prevalent epilepsy compared to those without.

## Key findings

- NPC patients with prevalent epilepsy showed significantly faster cognitive decline than those without epilepsy.
- Cognitive decline rates were similar between incident epilepsy and non-epilepsy groups.
- Controlling seizures may help reduce cognitive deterioration in NPC survivors.

## Abstract

Epilepsy is a common complication after radiotherapy and may lead to accelerated cognitive ageing. However, it is unknown whether and how much faster NPC patients with epilepsy experience cognitive decline beyond the expected radiotherapy-related cognitive change. Here, we utilized clinical data from a prospective, registry-based cohort study to compare the rates of cognitive decline among NPC survivors with or without epilepsy. Our results found that Global cognitive function declined more rapidly in NPC patients with prevalent epilepsy compared with those without epilepsy. It indicated that early identification and control of seizure attack is extremely valuable to mitigate cognitive decline.

Purpose: Cognitive decline is a major concern for nasopharyngeal carcinoma (NPC) survivors after radiotherapy (RT). We assessed whether the rates of cognitive decline in NPC survivors differed depending on the presence of epilepsy. Methods: Based on an ongoing prospective cohort study (NCT03908502), we included consecutive NPC patients with a history of radiotherapy who underwent a baseline and follow-up cognition assessment between January 2005 and December 2023. Patients who had a confirmed diagnosis of epilepsy before radiotherapy, had intracranial brain metastasis during follow-up, lacked baseline major clinical data, or lacked follow-up cognitive assessment of longer than six months were excluded. The outcome was cognitive function assessed by the Chinese version of the Montreal Cognitive Assessment (MoCA), with assessments being performed every 6 months through face-to-face interviews. Linear mixed-effect models were used to analyze the progression rate of MoCA scores by epilepsy status (incident, prevalent, or no epilepsy). Results: A total of 521 patients with a median follow-up period of 3.96 years were included in our study. The rate of decline in MoCA was significantly faster in patients with prevalent epilepsy compared with no epilepsy after adjusting for demographics, health behaviors, tumor-related history, complications, anti-seizure medication, and inflammatory blood index (estimate: −1.407; 95%CI: −2.419, −0.412; p = 0.007). However, the cognitive decline rate was similar in the incident epilepsy group compared with that in the non-epilepsy group (p = 0.126). Subgroup analysis showed that there was no significant difference in the effect of epilepsy status on cognitive deterioration among subgroups stratified by the pre-planned covariates. Conclusions: Global cognitive function declined more rapidly in NPC patients with prevalent epilepsy. The control of seizure attacks may be valuable to mitigate cognitive decline.