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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.
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1 University of California Irvine, Department of Clinical Pharmacy Practice, Irvine, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243)
2 National University of Singapore, Department of Pharmacy, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431)
3 KK Women and Children’s Hospital, Department of Pharmacy, Singapore, Singapore (GRID:grid.414963.d) (ISNI:0000 0000 8958 3388)
4 Flinders University, Caring Futures Institutes, College of Nursing and Health Sciences, Adelaide, Australia (GRID:grid.1014.4) (ISNI:0000 0004 0367 2697)
5 National University of Singapore, Department of Pharmacy, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431); National Cancer Centre Singapore, Department of Pharmacy, Singapore, Singapore (GRID:grid.410724.4) (ISNI:0000 0004 0620 9745)
6 National Cancer Centre Singapore, Division of Medical Oncology, Singapore, Singapore (GRID:grid.410724.4) (ISNI:0000 0004 0620 9745)
7 University of California Irvine, Department of Clinical Pharmacy Practice, Irvine, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243); National Cancer Centre Singapore, Department of Pharmacy, Singapore, Singapore (GRID:grid.410724.4) (ISNI:0000 0004 0620 9745)