Neural mechanisms of impaired executive function in untreated colorectal cancer patients.

Abstract

e24170 Background: Cancer-related cognitive impairment (CRCI) affects 45% of colorectal cancer (CRC) patients prior to treatment. This study aimed to explore the neural mechanisms of CRCI in this severely understudied population by using a combination of neuropsychological and cognitive neurophysiology assessments. Methods: Newly diagnosed Stage I-IV CRC patients were recruited at a Midwestern tertiary medical center. Enrollment criteria included normal or corrected to normal vision and no prior cancer within 3 years. Healthy comparisons were recruited and demographically-matched to Stage III/IV patients scheduled to receive chemotherapy. Participants completed neuropsychological measures of processing speed, psychomotor speed, executive function, and verbal memory at study baseline. We recorded scalp electroencephalography while participants performed a computer-based cognitive task designed to measure control over spatial attention. Two event-related potentials were measured following presentation of a task-irrelevant spatial cue: (1) N2, a neural correlate of stimulus selection emerging approximately 160 milliseconds after stimulus presentation; and (2) N2pc, a neural correlate of spatial attention allocation emerging approximately 200 milliseconds after stimulus presentation. Results: CRC patients were enrolled within 4-8 weeks following surgery for Stage I (11%), II (31%), and III (35%) CRC; Stage IV patients (23%) started chemotherapy without surgery. Patients (n = 26) and controls (n = 14) were matched on age and gender; patients were trending toward lower education than controls (p = .06). Patients performed worse than controls on executive function assessments (Trials B: p = .049; Stroop: p = .025). N2 amplitudes were smaller in patients than controls (p = 0.032. N2pc amplitudes were larger in patients than controls (p = .092). N2 amplitudes were associated with Stroop interference scores (r = 0.50, p = .068). Conclusions: CRC patients demonstrated impaired executive function performance at baseline. Neurophysiological data suggest impairments may emerge from limited neural resources available for stimulus selection and poor control over spatial attention. Correlations between neurophysiological data and executive function performance suggest participants better able to overcome task-irrelevant interference had relatively more neural resources available for stimulus selection. Overall, these results suggest patients may be limited in their ability to focus their attention on caregiver and health care team instructions. Clinical trial information: NCT03683004 .