Effect of Chemotherapy and Radiotherapy on Cognitive Function in Colorectal Cancer: Evidence from National Representative Longitudinal Database

Objectives We aimed to assess the risk of chemotherapy- and radiotherapy-related cognitive impairment in colorectal cancer patients. Methods Medical use data of colorectal cancer patients were obtained from Korean National Health Insurance Database (NHID), 2004-2018. We randomly selected 40% of colorectal cancer patients (N=148,848). Cognitive impairment cases were defined as having one or more ICD-10 diagnostic codes for dementia or mild cognitive impairment. Patients aged 18 or younger, patients diagnosed with cognitive impairment before colorectal cancer diagnosis (N=8,225) and those who did not receive primary resection (N=45,320) were excluded. The effects of each chemotherapy regimen on cognitive impairment were estimated. We additionally estimated the effect of radiotherapy in rectal cancer patients. Time-dependent competing risk Cox regression was conducted to estimate overall and age-specific hazard ratios (HR) separately for colon and rectal cancer. Landmark analyses with different lag times were conducted as sensitivity analyses. Results Chemotherapy did not increase the risk of cognitive impairment in colorectal cancer (colon cancer: HR=0.92, 95% CI 0.83-1.03; rectal cancer: HR=0.88, 95% CI 0.75-1.04). Radiotherapy was negatively associated with cognitive impairment in rectal cancer (HR=0.01, 95% CI 0.84-0.99). Heterogeneous direction of association by regimen combination was detected. Adverse cognitive effect of certain chemotherapy regimen was more prominent in elderly patients. Conclusion Chemotherapy and radiotherapy did not increase the risk of cognitive impairment. Elderly patients with low cognitive reserve could be affected by adverse cognitive effects of chemotherapy. Folate administration showed protective effect against possible cognitive impairment.