Neurotrophic-Inflammatory Imbalance and Cognitive Decline After Adjuvant Chemotherapy in Colon Cancer: A Prospective Cohort Study.

BACKGROUND

Cancer-related cognitive impairment (CRCI) is a prevalent yet underrecognized complication among colon cancer survivors that adversely affects quality of life and psychological well-being. Emerging evidence suggests that neurotrophic dysregulation and systemic inflammation may contribute to chemotherapy-related neurotoxicity; however, longitudinal biomarker-based data remain limited.

METHODS

In this prospective cohort study, 127 patients with resected colon cancer were evaluated at baseline and at the 6-month follow-up. Of these, 83 received adjuvant chemotherapy and 44 underwent postoperative surveillance alone. Cognitive performance (MoCA), depressive symptoms (HADS-D), and peripheral neuropathy (CIPN20) were assessed alongside serum brain-derived neurotrophic factor (BDNF) levels and systemic inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein-to-albumin ratio (CAR). Linear mixed model and logistic regression analyses were performed to identify factors associated with cognitive decline.

RESULTS

Adjuvant chemotherapy was associated with significant reductions in MoCA scores and serum BDNF levels (both p < 0.001), particularly among patients receiving the oxaliplatin-based XELOX regimen. Greater longitudinal reductions in BDNF (ΔBDNF) were independently associated with higher odds of CRCI (OR = 0.749 per 10 ng/mL increase in ΔBDNF, 95% CI: 0.658-0.854, p < 0.001). The model including ΔBDNF showed higher apparent discrimination than the corresponding model without ΔBDNF (AUC = 0.929 vs. 0.812).

CONCLUSION

Longitudinal reductions in serum BDNF were independently associated with CRCI among patients receiving adjuvant chemotherapy. These findings support a potential role for neurotrophic dysregulation in chemotherapy-related cognitive decline and highlight the need for further validation studies evaluating BDNF as a candidate biomarker for CRCI.