Cytokines as mediators of chemotherapy-associated cognitive changes: current evidence, limitations and directions for future research.

OBJECTIVES: While various clinical and pharmacological determinants for chemotherapy-associated cognitive impairment have been identified, conflicting evidence suggests that cytokines might play an intermediary role. The objective of this systematic review was to evaluate the current evidence pertaining to the associations among chemotherapy, cytokines induction and cognitive impairment in cancer patients. METHODS: A literature search with PubMed and SciVerse Scopus was conducted in March 2013 to gather relevant articles and abstracts that fulfilled the inclusion and exclusion criteria. This review included studies that had performed objective and/or subjective cognitive assessments and cytokine measurements on defined populations of cancer patients who received chemotherapy. RESULTS: High methodological heterogeneity existed among the selected studies which differed in cancer populations, subject characteristics, cognitive endpoints, types of cytokines tested and their measurement methods. Weak to moderate correlations were observed between IL-1ß, IL-6, TNF-α levels, and different degrees of cognitive impairment. Different types of chemotherapy treatments might lead to varying presentations and severities of cytokine-induced cognitive impairment. Notably, the time concordance between the onset of cytokine induction and occurrence of cognitive impairment was not well elucidated. A number of confounding factors was identified to interfere with the expression levels of cytokines; these confounders included subjects' cancer types, ages, genders, genetics and psychosocial characteristics such as anxiety, depression and fatigue. CONCLUSION: Although existing studies observed cognitive impairment and cytokine dysregulation in patients who receive chemotherapy, our results suggest that the intermediary role of cytokines in post-chemotherapy cognitive impairment is still controversial and requires further evaluation. A list of methodological recommendations is proposed to harmonize future studies of this subject matter.

Psychometric properties and measurement equivalence of the English and Chinese versions of the functional assessment of cancer therapy-cognitive in Asian patients with breast cancer.

OBJECTIVE: This study was designed to examine the psychometric properties and measurement equivalence of the English and Chinese versions of the Functional Assessment of Cancer Therapy-Cognitive Function (Version 3) (FACT-Cog) in multiethnic Asian patients with breast cancer. METHODS: This prospective study involved patients with breast cancer from the National Cancer Centre Singapore. The concurrent validity of the FACT-Cog was assessed according to its strength of correlation with the validated European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 cognitive functioning scale, and its association with fatigue, global health status, and anxiety. The known-group validity was assessed on the basis of receipt of chemotherapy. Factor analysis was conducted to ascertain the one-factor structure of each cognitive domain. The reliability was evaluated by using Cronbach's alpha and intraclass correlation coefficient within the cognitive domains. Multiple regression analyses were performed to compare the total scores between the two language versions, adjusting for covariates. RESULTS: A total of 185 English-speaking and 143 Chinese-speaking patients were recruited. Both the English and Chinese FACT-Cog total scores correlated strongly with the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 cognitive functioning scale scores (r = 0.725 and 0.646), whereas correlations with fatigue, anxiety, and global health status were weak to moderate (|r| = 0.376-0.589). Regarding the known-group validity, more severe perceived cognitive disturbance was observed among patients receiving chemotherapy than among those who were not for both versions (P = .010 and .008, respectively). Internal consistencies within the cognitive domains were high (Cronbach's α 0.707-0.929), and test-retest reliability was satisfactory for both versions (intraclass correlation coefficient 0.762 and 0.697). The measurement equivalence between the English and Chinese versions was established for all domains except the multitasking domain. CONCLUSION: The English and Chinese versions of the FACT-Cog are valid, reliable, and equivalent for clinical and research use.