Longitudinal observation of radiation-induced cognitive impairment and emotional dysfunction: Based on animal model and clinical cohort

Abstract

Radiation-induced cognitive impairment (RICI) and emotional disorder (RIED) are comorbidities that seriously affect the quality of life in patients with radiation-induced brain injury (RIBI). A longitudinal study was conducted to observe the occurrence and development of RICI and RIED in an RIBI animal model and a clinical cohort following intensity modulated radiotherapy (IMRT). RIBI mice and sham controls were subjected to three cycles of behavior tests for cognitive and emotional function at post-irradiation 1 week (1w), 5 weeks (5w), and 9 weeks (9w) corresponding to early, middle and late stage after radiotherapy. Additionally, 139 patients who underwent IMRT after nasopharyngeal carcinoma and were firstly diagnosed with radiation-induced brain injury were enrolled. Pre-treatment and follow-up neuropsychological assessments of cognition, anxiety and depression were completed. Compared with control, significant declines in working memory, object recognition memory and social memory were observed in RIBI mice at post-irradiation 5w and 9w. Longitudinal observations revealed that memory impairment predominantly occurred in the middle stage and persisted into the late stage. Anxiety-like behaviors were only observed at post-irradiation 9w. In the clinical cohort, RICI exhibited a parallel cumulative incidence curve and a similar median onset to RIBI. RICI predominantly occurred 2–6 years post-IMRT 2–6 and progressively deteriorated beyond 6 years while RIED gradually increased beyond 6 years after IMRT. During two-year follow-up visits, half of the patients with RICI combined with RIBI benefited from drug treatment, achieving stable or improved cognition, while the other half showed no response or experienced cognition aggravation. In summary, RICI predominantly occurred in the middle stage post-irradiation and progressed to the late stage while RIED mostly emerged in the late stage in RIBI. Consistency in the development process of RICI and RIED was observed in the animal model and the clinical cohort.