Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: impact of age and cognitive reserve

Abstract

Purpose: To examine the impact of age and cognitive reserve on cognitive functioning in patients with breast cancer who are receiving adjuvant treatments.

Patients and methods: Patients with breast cancer exposed to chemotherapy (n = 60; mean age, 51.7 years) were evaluated with a battery of neuropsychological and psychological tests before treatment and at 1, 6, and 18 months after treatment. Patients not exposed to chemotherapy (n = 72; mean age, 56.6 years) and healthy controls (n = 45; mean age, 52.9 years) were assessed at matched intervals.

Results: Mixed-effects modeling revealed significant effects for the Processing Speed and Verbal Ability domains. For Processing Speed, a three-way interaction among treatment group, age, and baseline cognitive reserve (P < .001) revealed that older patients with lower baseline cognitive reserve who were exposed to chemotherapy had lower performance on Processing Speed compared with patients not exposed to chemotherapy (P = .003) and controls (P < .001). A significant group by time interaction for Verbal Ability (P = .01) suggested that the healthy controls and no chemotherapy groups improved over time. The chemotherapy group failed to improve at 1 month after treatment but improved during the last two follow-up assessments. Exploratory analyses suggested a negative effect of tamoxifen on Processing Speed (P = .036) and Verbal Memory (P = .05) in the no-chemotherapy group.

Conclusion: These data demonstrated that age and pretreatment cognitive reserve were related to post-treatment decline in Processing Speed in women exposed to chemotherapy and that chemotherapy had a short-term impact on Verbal Ability. Exploratory analysis of the impact of tamoxifen suggests that this pattern of results may be due to a combination of chemotherapy and tamoxifen.

Fig 1.

Pre- to post-treatment change in processing speed by treatment, age groups, and level of cognitive reserve. (A) Wide Range Achievement Test (WRAT-3) below median; (B) WRAT-3 above median. High and low pretreatment cognitive reserve were defined by a median split on the WRAT-3 reading score of less than 0.0 or of greater than or equal to 0.0. The bar heights represent the observed post-treatment averages pooled across three assessment time points. The error bars represent the estimated standard errors of the averages accounting for repeated assessments from the same individuals.

Fig 2.

Adjusted verbal ability scores (z-scale) by group across time. Tx, treatment; M, months.