Chemotherapy Induced Cognitive Impairment in Acute Lymphoblastic Leukemia Survivors: White Matter pathologies and interventions

Acute Lymphoblastic Leukemia (ALL) is the most common cancer type among children, affecting millions worldwide. Developments in cancer treatment raised its 5 year survival rate to its present 90%. However, some survivors of ALL experience neurocognitive impairment related to their chemotherapy exposure, even years after their treatment. These negative effects of chemotherapy on the brain and cognition are called Chemotherapy Induced Cognitive Impairment (CICI) and affect many cognitive domains, including memory, attention and executive functions. Even though CICI can be observed in survivors of many different cancer types, it is more likely to occur when the chemotherapy includes anti-metabolite drugs, such as methotrexate (MTX). The neurobiological mechanisms behind CICI are not completely understood. However, neuroimaging studies in ALL survivors report long-term White Matter (WM) abnormalities, indicating that WM defects and poor myelination may underlie CICI. The current project aims to investigate the changes in behavior, brain function and WM microstructure in a refined animal model that mimics late CICI in adult survivors of ALL. Moreover, it includes hypothesis-driven pharmacological and non-pharmacological experiments that could lead the way to an effective clinical intervention.