Cognitive Decline Observed Six Months After Chemotherapy in Patients With Lymphoma

Patients with lymphoma tend to report and show signs of worsening cognitive function at six months after chemotherapy compared with healthy controls, according to study findings recently published in the Journal of the National Care Institute.

Corresponding study author Michelle C. Janelsins, PhD, of the James P. Wilmot Cancer Institute in Rochester, New York, told ASH Clinical News that cognitive problems appear to be “something for clinicians treating patients with lymphoma to be aware of and monitor during treatment,” given the potential impact of cancer-related cognitive decline on quality of life and treatment outcomes.

Dr. Janelsins and colleagues assessed longitudinal changes in memory, attention, and executive function in men and women with lymphoma (n=248; 62.5% male) prior to and six months after initiation of chemotherapy. Standardized cognitive assessments and self-reported measures were used to evaluate cognition during the study.

A group of age- and sex-matched people without cancer was used as a control arm (n=212; 59% male). In addition to the comparison of cognitive changes between patients and controls, the researchers also examined differences in cognitive function between men and women, between patients with Hodgkin lymphoma versus non-Hodgkin lymphoma (n=186), and by disease subtype.

Cognitive assessments were performed at the following intervals:

  • baseline (A1): within 7 days of the first chemotherapy session
  • post-chemotherapy (A2): within 1 month after the last chemotherapy session
  • follow-up (A3): at 6 months after the last chemotherapy session

At baseline, patients with lymphoma self-reported significantly more issues on the FACT-Cog scale (perceived cognitive impairment [PCI] and total scores) compared with sex-matched controls (p<0.05). In addition, patients with lymphoma reported significantly more attentional difficulty (p=0.01) and significantly greater PCI from A1 to A2, as well as from A1 to A3 (p<0.03).

There was no difference in baseline objective memory test scores between patients with lymphoma and controls. From periods A1 to A2, however, patients performed worse than controls on tests of immediate recall (p=0.01). Patients also showed less improvement in immediate recall over time from periods A1 to A3 (p=0.02). Patients with lymphoma also had poorer performance from A1 to A2 and from A1 to A3 on a phone-based immediate and delayed recall test (p<0.001).

Patients with lymphoma also performed less well on tests for attention from A1 to A2 relative to controls (p=0.02). In tests of executive function, patients performed lower than controls (p=0.02). Patients with lymphoma also performed significantly less well from A1 to A2 as well as from A1 to A3 on the phone-based Digits Backward test (p<0.001 and p=0.01, respectively) and Category Fluency tests (all p<0.001).

In the subgroup analysis according to patient sex, the researchers observed that women with lymphoma had a higher perceived impairment in cognition than men with lymphoma, relative to controls, from A1 to A2 and from A1 to A3 (p=0.007).

Looking specifically at the female study population, 51.3% of women with lymphoma reported a perceived decline in FACT-Cog PCI scores compared with only 14.5% of women in the control group (p<0.001). At six-month follow-up, a higher proportion of women with lymphoma reported decline in FACT-Cog scores compared with women in the control arm (54.8% vs. 11.7%; p<0.001). In the male population, more men with lymphoma reported declines in FACT-Cog scores at six months following chemotherapy compared with controls (37.8% vs. 15.1%; p<0.001). The researchers noted that women with lymphoma reported statistically significantly more perceived impairment compared to men with lymphoma and controls.

Limitations of this study included its relatively small sample sizes for subgroups, which the researchers suggest may have led to a lack of difference in cognitive function outcomes between patients by treatment regimen or lymphoma type. Additionally, the study is limited by its short follow-up period. “Future studies should be designed to address differences of the impact of disease subtypes and treatment on cognitive function, including those receiving more targeted therapies and immunotherapy,” the authors concluded.

The authors report no relevant conflicts of interest.


Janelsins MC, Mohamed M, Peppone LJ, et al. Longitudinal changes in cognitive function in a nationwide cohort study of patients with lymphoma treated with chemotherapy [published online ahead of print, 2021 Jul 13]. J Natl Cancer Inst. doi: 10.1093/jnci/djab133.