An observational study to explore the involvement of inflammation and depression on the occurrence of chemotherapy-related cognitive impairment in lymphoma patients

Patients with cancer oftencomplain of cognitive problems during their treatment and chemotherapy-related cognitiveimpairment (CRCI)remains an important clinical issue in such patients. CRCI also known as ‘chemobrain’, occursin 17–75% of patients with various malignancies treatedwith chemotherapeutic agents that worsen the quality of life. Depression is one of the most prevalentpsychological symptoms perceived by cancer patients. It worsens during chemotherapy, persists for a long timeafter the end of chemotherapy, is also manifested in the recurrence of thedisease and finally consists an independent prognostic factor for mortality**.** Depression leads to a poorerquality of life (QOL) and compromises patient outcomes, with depressionresulting in higher rates of mortality in cancer.

Cytokinedysregulation is thought to play an important role in the pathogenesis of CRCI.Chemotherapy can induce an immune reaction that subsequently causes highlyelevated levels of various cytokines via a positive feedback loop betweencytokines and white blood cells. Small quantities of chemotherapeutic drugs cancross the blood-brain barrier and enter the brain, resulting in overproductionof pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosisfactor-α(TNF-α), and suppression of anti-inflammatory cytokines, such as IL-4and IL-10. Pro-inflammatory cytokines elicited by chemotherapy of peripheralnormal and tumor tissues also can cross the blood-brain barrier, damageneuronal cells in the brain, and disrupt the blood-brain barrier integrity andtransport mechanisms, further leading to the overflow of chemotherapeutic drugsinto the brain. Pro-inflammatory cytokines have considerable toxic effects onneuronal cells, particularly those in the hippocampus and the pre-frontalcortex associated with cognitive functions, as they are more susceptible toneurotoxin insults. Existing evidence suggests thatinflammatory cytokines increases during chemotherapy which plays anintermediary role in CRCI. Severalclinical studies have revealed that higher blood concentration of IL-6 isassociated with poorer cognitive performance, but the elevated level of IL-4 isprotective against chemobrain in breast cancer patients. A similar study conducted in our centre has alsodemonstrated the occurrence of cognitive impairment after chemotherapyadministration in lymphoma patients. These studies have led to thehypothesis that chemotherapy-induced cytokine dysregulation and disruptedneuroplasticity in related brain regions may lead to the development of CRCI. This intermediary roleof cytokines in CRCI is still controversial and requires further evaluation.

In view of the above observations the aim of thepresent study is to explore the involvement of inflammation and depression onthe occurrence of chemotherapy-related cognitive impairment in lymphomapatients.