Longitudinal observation of radiation-induced cognitive impairment and emotional dysfunction combined with radiation-induced brain injury: Based on animal model and clinical cohort.

Abstract

Background: Radiation-induced cognitive impairment (RICI) and emotional disorder (RIED) are comorbidity which seriously affect the quality of life in radiation-induced brain injury (RIBI) patients.

Purpose: Longitudinal observation on occurrence and development process of RICI and RIED was made in RIBI animal model and RIBI clinical cohort after IMRT.

Methods: RIBI mice and sham control were subjected to three cycles of behavior tests for cognitive and emotional function at post-irradiation 1w, 5w, 9w which corresponded with early, middle and late stage after IMRT. And 139 patients who underwent IMRT after NPC and firstly diagnosed with radiation-induced brain injury were enrolled. Pre-treatment and follow-up neuropsychological assessment of cognition, anxiety and depression were completed.

Results: Compared with control, significant decline in working memory, object recognition memory and social memory was observed in RIBI mice at post-irradiation 5w (middle stage, p < 0.001, p < 0.05 and 0.0781) and post-irradiation 9w (late stage, all p < 0.01). From longitudinal observations, memory impairment mostly occurred at middle stage (both p < 0.05) and maintained to late stage. Anxiety-like behaviors were only observed at post-irradiation 9w (late stage, all p < 0.05). In the clinical cohort, RICI had parallel tendency of cumulative curve and close median onset compared with RIBI. RICI intensively occurred in post-IMRT 2-6 years and progressively deteriorated to post-IMRT > 6 years while RIED occurred and gradually increased at post-IMRT > 6 years. During two-year follow-up visits, half of patients with RICI combined with RIBI benefited from conventional treatment to obtain stable or improved cognition, while the other half of patients had no response or cognition aggravation.

Conclusions: RICI intensively occurred in post-irradiation middle stage and progressed to late stage while RIED occurred mostly in late stage in RIBI. Consistency of RICI and RIED development process was observed.