Pharmacological and therapeutic innovation to mitigate radiation-induced cognitive decline (RICD) in brain tumor patients

Radiation therapy is a key treatment modality in both primary and metastatic brain tumors. However, despite its efficacy, it often results in cognitive decline, particularly after whole brain RT (WBRT). Radiation-induced cognitive impairment, which affects memory, attention, and executive function, significantly affects Quality Of Life (QOL) and functional independence. Although white matter necrosis, a hallmark of conventional radiation techniques, has become less common with modern methods, cognitive deficits remain a persistent issue. Neuroinflammation is a key driver of this decline, along with disruptions in hippocampal neurogenesis and damage to regions of the brain. Radiation affects neural stem cells, mature neurons, and glial cells, particularly within the hippocampus, affecting cognition. Recent studies suggest that targeting neuroinflammation and other key Signaling pathways (NMDAR, RAAS, PARP, PPAR, etc.) can reduce cognitive impairment. This review examines the theme of radiation-induced cognitive decline and explores possible interventions to prevent or mitigate these outcomes.