Cognitive Function in Patients With Colorectal Cancer Who Do and Do Not Receive Chemotherapy: A Prospective, Longitudinal, Controlled Study

Abstract

Purpose: Cognitive dysfunction is reported in people with cancer. Therefore, we evaluated longitudinal changes in cognitive function and underlying mechanisms in people with colorectal cancer (CRC) and healthy controls (HCs).

Patients and methods: Participants completed cognitive assessments and questionnaires reporting cognitive symptoms, fatigue, quality of life, and anxiety/depression at baseline (before chemotherapy, if given) and 6, 12, and 24 months. Blood tests included cytokines, clotting factors, apolipoprotein E genotype, and sex hormones. Primary end point was overall cognitive function measured by the Global Deficit Score at 12 months.

Results: We recruited 289 patients with localized CRC (173 received chemotherapy; median age, 59 years; 63% male), 73 patients with limited metastatic/recurrent CRC, and 72 HCs. Cognitive impairment was more frequent in patients with localized CRC than HCs at baseline (43% v 15%, respectively; P < .001) and 12 months (46% v 13%, respectively; P < .001), with no significant effect of chemotherapy. Attention/working memory, verbal learning/memory, and complex processing speed were most affected. Cognitive impairment was similar in patients with localized and metastatic CRC. Cytokine levels were elevated in patients with CRC compared with HCs. There was no association between overall cognitive function and fatigue, quality of life, anxiety/depression, or any blood test. Cognitive symptoms at 12 months were reported in 25% of patients with localized CRC versus 17% of HCs (P = .19). More participants who received chemotherapy had cognitive symptoms at 6 months (32%) versus those who did not (16%; P = .007), with no significant difference at 12 months (29% v 21%, respectively; P = .19). Objective cognitive function was only weakly associated with cognitive symptoms.

Conclusion: Patients with CRC had substantially more cognitive impairment at every assessment than HCs, with no significant added effect of chemotherapy. Mechanisms of cognitive impairment remain unknown.

Fig 1.

CONSORT diagram. CRC, colorectal cancer; CTh+, received adjuvant chemotherapy; CTh–, did not receive adjuvant chemotherapy.

Fig 2.

Prevalence of overall neuropsychological impairment (NPI) by study group and visit. (A) Global Deficit Score (GDS) on clinical neuropsychological tests (the primary end point). (B) International Cancer and Cognition Task Force (ICCTF) criteria on clinical neuropsychological tests. (C) GDS on Cambridge Neuropsychological Test Automated Battery tests. NPI is defined as GDS greater than 0.5, and GDS is adjusted for practice effect at 6-, 12-, and 24-month visits. ICCTF criteria are defined as T score less than 1.5 standard deviations (SDs) below the mean (T < 35) on two tests or T score less than 2 SDs (T < 30) on one test. CRC, colorectal cancer; CTh+, received adjuvant chemotherapy; CTh–, did not receive adjuvant chemotherapy.

Fig 3.

Change in neuropsychological functioning from baseline using 5% (top and bottom) of regression-based summary scores. CRC, colorectal cancer; CTh+, received adjuvant chemotherapy; CTh–, did not receive adjuvant chemotherapy.