The Impact of Using Different Reference Populations on Measurement of Breast Cancer-Related Cognitive Impairment Rates

Document Type


Publication Date



Cancer, Oncology, Cognition, Methods, Measurement

Digital Object Identifier (DOI)



Objective: To evaluate how use of different reference populations affects estimates of breast cancer-related cognitive impairment rates. Methods: Patients aged ≥60 years with stage 0–3 breast cancer (n = 371) and matched non-cancer controls (n = 370) completed 13 neuropsychological tests prior to systemic therapy or at enrollment (controls). The tests captured three domains: attention, processing speed and executive function; learning and memory; and visual-spatial function. Domain-specific impairment was defined as having one test score 2 SD below or two or more test scores 1.5 SD below the reference population means. Different reference populations were used to define impairment: published normative data, study-specific controls, age and education-stratified controls, and age and education-adjusted controls. The associations between the resultant impairment rates and breast cancer (vs. control) were evaluated using chi-square tests and logistic regression models. Cohen’s kappa coefficients were used to evaluate agreement of impairment rates between study-specific control performance and the other reference population groups. Results: The patients and controls were aged 68.0 (SD 6.0) and 67.9 (SD 7.0) years, respectively. The association of breast cancer-control status with impairment did not differ based on reference group. Cognitive impairment based on published normative data yielded less agreement on impairment rates (κ = 0.22–0.89) than study-specific age and education-stratified control performance (κ = 0.62–1.00). Conclusion: The choice of reference populations did not affect conclusions about the association of cognition with breast cancer. However, while study-specific reference populations provided greater internal consistency in defining cognitive impairment, benchmarking against published normative data will enhance the ability to compare results across studies.

Was this content written or created while at USF?


Citation / Publisher Attribution

Archives of Clinical Neuropsychology, v. 33, issue 8, p. 956-963