Radiation-induced cognitive impairment-from bench to bedside

Abstract

Approximately 100,000 patients per year in the United States with primary and metastatic brain tumor survive long enough (>6 months) to develop radiation-induced brain injury. Before 1970, the human brain was thought to be radioresistant; the acute central nervous system (CNS) syndrome occurs after single doses of ≥ 30 Gy, and white matter necrosis can occur at fractionated doses of ≥ 60 Gy. Although white matter necrosis is uncommon with modern radiation therapy techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become increasingly important, having profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenic mechanisms involved in radiation-induced cognitive impairment. Although reductions in hippocampal neurogenesis and hippocampal-dependent cognitive function have been observed in rodent models, it is important to recognize that other brain regions are affected; non-hippocampal-dependent reductions in cognitive function occur. Neuroinflammation is viewed as playing a major role in radiation-induced cognitive impairment. During the past 5 years, several preclinical studies have demonstrated that interventional therapies aimed at modulating neuroinflammation can prevent/ameliorate radiation-induced cognitive impairment independent of changes in neurogenesis. Translating these exciting preclinical findings to the clinic offers the promise of improving the quality of life in patients with brain tumors who receive radiation therapy.

Cranial irradiation compromises neuronal architecture in the hippocampus

“…The capability of dendritic spines to rapidly respond to transmembrane signals, including those associated with behavior, hormonal status, and synaptic activity and various forms of stress, indicate their critical role in learning and memory (32,33). The fact that radiation exposure leads to reduced spine density and, in particular, inhibits the formation of immature filopodia, is consistent with the adverse neurocognitive sequlae documented in brain cancer survivors subjected to cranial radiotherapy (1,34). The persistence of these structural changes coincides with the protracted recovery of the irradiated CNS, and is again consistent with the progressive and irreversible nature of radiation-induced cognitive dysfunction (11,35).…”

The Current Utilization of Cognitive Tests in the Research of Radiation-Induced Cognitive Dysfunction in Rodent Models

“…It is characterized by decreased verbal memory, spatial memory, attention, and novel problem-solving ability [9,24]. Cognitive dysfunction progresses to dementia in approximately 2% to 5% of long-term survivors who have received WBI, including memory loss, ataxia, and urinary incontinence.…”

“…The mechanisms of radiation-induced cognitive dysfunction are not yet fully understood. According to the available knowledge, radiation-induced cognitive dysfunction is hypothesized to result from dynamic interactions between multiple cell types: vascular and glial clonogens, neurogenesis, neural function and neuroinflammation [8][9][10]. Therefore, studies into the mechanisms and preventive measures of radiation-induced cognitive dysfunction are of paramount importance to decrease the side effects of WBI and increase the quality of life of patients.…”

Post-Operative Cognitive Dysfunction in Cancer Patients: A Narrative Review

“…In addition, functional deficits like progressive impairments in memory, attention, and executive function may also occur. These structural and functional changes have been observed to have profound effects on quality of life (QOL) of cancer survivors [12].…”