Potential Pathways for Chemotherapy-Induced Cognitive Decline

Cognitive dysfunction is an adverse effect of antineoplastic agents. The number of cancer patient survivors is increasing nowadays, but along with this achievement, the side effects of chemotherapy are also developing simultaneously. One of the adverse effects, CICI (chemotherapy-induced cognitive impairment), also known as “chemofog” or “chemobrain,” brings huge challenges in front of cancer survivors after successful chemotherapy. Around 75% of patients experience CICI during the treatment and another 35% experience it after the treatment. Patients have symptoms such as impairments in visual-verbal memory, awareness, working ability, concentration, attention, executive functions, fatigue, and behavioral dysfunctions that adversely affect the quality of life of cancer survivors. Apart from this, clinical reports demonstrated associated mood disorders with vascular complications and seizures in some cases. Many mechanistic candidates have been studied, including disruption of the blood-brain barrier (BBB), suppressed hippocampal neurogenesis, neuronal growth, disruption, cell death, white matter abnormalities, inflammatory response, increased oxidative stress, and brain blood flow impairment. Oxidative stress is considered a vital mechanism since over 50% of FDA-approved anticancer drugs can generate reactive oxygen species (ROS) or reactive nitrogen species (RNS), which lead to neuronal death. Chemobrain pathology has been hypothesized as a multifactorial process causing cognitive dysfunction via the interaction of several mechanisms, as it is not a single mechanism that can be considered the reason for developing chemobrain. Here we will discuss in an overview some of CICI’s most possible underlying mechanisms.