Subjective cognition and mood in persistent chemotherapy-related cognitive impairment

Abstract

Purpose: Persistent chemotherapy-related cognitive impairment (CRCI) is commonly reported following cancer treatment and negatively affects quality of life. While past research has focused on potential pathophysiological mechanisms underlying this relationship, the role of psychological factors, such as mood, stress, and anxiety, in the development of persistent CRCI has received less attention. As an additional analysis of data from a trial investigating the effects of transdermal nicotine patches on cognitive performance in patients with persistent CRCI, we examined whether change in mood was associated with changes in subjective and objective cognitive functioning.

Methods: Participants were randomized to either placebo (n = 11) or transdermal nicotine (n = 11) for 6 weeks, followed by 2 weeks of treatment withdrawal for a total of 8 weeks. Participants were assessed using behavioral, subjective, and objective measures of cognitive functioning and mood at five visits before, during, and after treatment.

Results: Although we did not detect an effect of treatment assignment on mood, over the course of the study, we observed a significant improvement on measures of mood that correlated with improvement in subjective and objective cognitive performance.

Conclusions: We observed improvement in objective and subjective cognitive performance measures. These changes were associated with improvement in subsyndromal mood symptoms, likely resulting from participation in the trial itself.

Implications for cancer survivors: These results suggest that women with persistent CRCI may benefit from support and validation of their cognitive complaints, cognitive rehabilitation/therapies into their post-cancer care.

Trial registration: The study was registered with clinicaltrials.gov (trial registration: NCT02312943).

Keywords: Breast cancer; Chemotherapy-related cognitive impairment; Cognitive impairment; Survivorship.

Fig. 1

Participants enrollment. a Overall pCRCI study design. The study consisted of two phases, a double-blind portion and an optional open-label portion. In the double-blind portion of the study, participants were first screened to determine study eligibility. Once cleared for the study, participants completed a baseline visit (Visit 2) and were then randomized (50/50) to receive either transdermal nicotine or placebo patches. Participants then repeated their baseline cognitive assessment at Visits 3 and 4 following 3 and 6 weeks on patches, respectively. After completing 6 weeks on patches, participants went off patches for 2 weeks and then repeated their baseline cognitive testing at their final double-blind study visit (Visit 5). b Participant enrollment. Of the 106 people pre-screened for the study, 37 were screened at Visit 1. Of the 37 screened at Visit 1, 25 people passed screening criteria and were randomized to treatment after completing Visit 2. Twelve were randomized to nicotine treatment (9 completers, 11 with usable data), and 13 were randomized to placebo treatment (11 completers) (figure adapted from Vega et al., 2019)

Fig. 2

POMS change from baseline scores. a POMS Total Mood Disturbance (TMD) change from baseline scores. Treatment groups are distinguished by the following colors: nicotine (black triangles) and placebo (white circles). The grey dashed lines indicate that participants were off patches between Visits 4 and 5. Negative TMD change scores indicate improved mood. b POMS Total Mood Disturbance (TMD) change from baseline scores for combined groups. Negative TMD change scores indicate improved mood. c POMS-Depression change from baseline scores; negative change scores indicate improvement in mood. d POMS-Fatigue change from baseline scores; negative change scores indicate improvement in mood e POMS-Confusion change from baseline scores; negative change scores indicate improvement in mood. f POMS-Vigor/Activity change from baseline scores; positive change scores indicate improvement in mood. Purple square markers indicate combined nicotine and placebo group data. The grey dashed lines indicate that participants were off patches between Visits 4 and 5. For all graphs, error bars indicate SE. Asterisks indicate significant pairwise differences between visits, *p < 0.05. All post-hoc pairwise comparisons are Sidak corrected for multiple comparisons

Fig. 3

Scatterplots for significant correlations between FACT-Cog subscales and Profile of Mood States (POMS)-Confusion percent change scores. a Correlation between FACT-Cog Perceived Cognitive Impairment (PCI) percent change score and POMS-Confusion percent change score. b Correlation between FACT-Cog Perceived Cognitive Abilities (PCA) percent change score and POMS-Confusion percent change score. c Correlation between FACT-Cog Quality of Life (QOL) percent change score and POMS-Confusion percent change score. d Correlation between FACT-Cog Total percent change score and POMS-Confusion percent change score. Treatment groups are distinguished by the following colors: nicotine (black triangles) and placebo (white circles). For all graphs, lower FACT-Cog scores were associated with higher POMS-Confusion scores. Higher FACT-Cog PCI scores indicate better subjective cognition. Lower POMS-Confusion scores indicate better mood

Fig. 4

Scatterplots for significant correlations between Profile of Mood States (POMS)-Confusion percent change scores and objective testing. a Correlation between POMS-Fatigue percent change score and CRT Recognition Time percent change score. b Correlation between POMS-Fatigue percent change score and ID Task percent change score. c Correlation between POMS-Fatigue percent change score and Detection Task percent change score. d Correlation between POMS-Confusion percent change score and CRT Total Reaction Time percent change score. Treatment groups are distinguished by the following colors: nicotine (black triangles) and placebo (white circles). Lower objective test scores indicate better performance. Lower POMS scores indicate improved mood