Longitudinal Changes in Cognitive Function in a Nationwide Cohort Study of Patients with Lymphoma Treated with Chemotherapy

J Natl Cancer Inst. 2021 Jul 13;djab133. doi: 10.1093/jnci/djab133. Online ahead of print.


Background: Cancer-related cognitive decline (CRCD) is an important clinical problem but limited research exists on assessment of cognitive function in patients with lymphoma.

Methods: The overall objective of this nationwide, prospective, observational study conducted in the NCI Community Clinical Oncology Research Program (NCORP) was to assess changes in memory, attention, and executive function in patients with lymphoma from pre- (A1) to post-chemotherapy (A2) and to six months post-chemotherapy (A3). Individuals without cancer served as non-cancer controls, paired to patients by age and gender, and were assessed at the same time-equivalent points. Longitudinal mixed models (LMM) including A1, A2, and A3 and adjusting for age, education, race, gender, cognitive reserve score, baseline anxiety and depressive symptoms were fit. We assessed changes in patients compared to controls and assessed differences in cognitive function in those patients with Hodgkins vs. Non-Hodgkins disease, and by disease subtype. All statistical tests were 2-sided.

Results: Patients with lymphoma (n = 248) and controls (n = 212) were recruited from 19 NCORP sites. From pre- to post-chemotherapy, and from pre-chemotherapy to 6 months follow-up, patients reported more cognitive problems over time compared to controls (FACT-Cog PCI Effect Size (ES) = 0.83 and 0.84 for A1 to A2 and A1 to A3, respectively; p < .001; single item cognitive symptoms ES = 0.55 and 0.70 for A1 to A2 and A1 to A3, respectively; p < .001); the complaints were more pronounced in women with lymphoma compared to men with lymphoma (FACT-Cog PCI Group x Time x Gender interaction p = .007). Patients with lymphoma also performed statistically significantly less well on tests of verbal memory and delayed recall, attention and executive function, and telephone-based category fluency.

Conclusion: Patients with lymphoma experience worse patient-reported and objectively assessed cognitive function from pre-chemotherapy to 6-month follow-up compared to age- and gender-paired controls assessed at similar time intervals.