Brain-derived neurotrophic factor as a biomarker in cancer-related cognitive impairment among adolescent and young adult cancer patients

Abstract

Brain-derived neurotrophic factor (BDNF) improves cognitive function by stimulating neurogenesis and neuroplasticity. We hypothesize that higher plasma BDNF levels are protective against cognitive toxicity among adolescent and young adult cancer patients (15–39 years old). In a prospective, longitudinal study, we recruited 74 newly diagnosed cancer and 118 age-matched non-cancer controls who completed the Cambridge Neuropsychological Test Automated Battery (CANTAB), Functional Assessment of Cancer Therapy-Cognitive Function questionnaire (FACT-Cog) and blood draws. Plasma BDNF was quantified using an enzyme-linked immunosorbent assay. Genomic DNA from buffy coat was genotyped for BDNF Val66Met. Most cancer participants were diagnosed with breast (24%) and head/neck (22%) cancers. After adjusting for sociodemographic variables (age, gender, race, marital status, education years), cancer participants had lower BDNF levels (ng/mL) at baseline (median: 10.7 vs 21.6, p < 0.001) and 6-months post-baseline (median: 8.2 vs 15.3, p = 0.001) compared to non-cancer controls. Through linear mixed modelling adjusted for sociodemographic variables, baseline cognition, fatigue, psychological distress, and time, we observed that among cancer participants, lower baseline BDNF levels were associated with worse attention (p = 0.029), memory (p = 0.018) and self-perceived cognitive abilities (p = 0.020) during cancer treatment. Met/Met was associated with enhanced executive function compared to Val/Val (p = 0.012). Plasma BDNF may serve as a predictive biomarker of cancer-related cognitive impairment.

Dynamin-1 is a potential mediator in Cancer-Related Cognitive Impairment

“…Subjective cognition is arguably a more accurate reflection of how cognitive changes can affect daily functioning compared to objective cognition which is often criticized for the lack of ecological validity 32,33 . While subjective and objective cognitive function may not match for individual patients [34][35][36] , biomarkers of CRCI, such as pro-inflammatory IL-6 and TNFα, as well as neurogenesis factor BDNF have found consistent directional correlations in studies utilizing both types of cognitive measures 12,30,37 Our breast cancer chemobrain animal model data has added new dimensions of preliminary data that validated the downregulation of hippocampal DNM1 levels exposed to chemotherapy. We found the most drastic reductions in the DNM1 immunoreactivity in the breast cancer-bearing mice (Py230) brains treated with adjuvant chemotherapy (ADR-CYP).…”

“…Subjective cognition is arguably a more accurate reflection of how cognitive changes can affect daily functioning compared to objective cognition which is often criticized for the lack of ecological validity 32,33 . While subjective and objective cognitive function may not match for individual patients 34–36 , biomarkers of CRCI, such as pro-inflammatory IL-6 and TNFα, as well as neurogenesis factor BDNF have found consistent directional correlations in studies utilizing both types of cognitive measures 12,30,37 . The biological underpinnings of both dimensions of cognition might be more similar than expected.…”

“…All participants completed questionnaires for evaluating perceived cognitive function (FACT-Cog) and neuropsychiatric symptoms (MFSI-SF and RSCL) and provided blood samples at all time points. Sociodemographic and cancer-related characteristics were collected from baseline surveys and medical records 11,12 .…”