title: Neuromarkers of fatigue and cognitive complaints following chemotherapy for breast cancer: a prospective fMRI investigation.
abstract: The aim of this study is to use functional magnetic resonance imaging (fMRI) to prospectively examine pre-treatment predictors of post-treatment fatigue and cognitive dysfunction in women treated with adjuvant chemotherapy for breast cancer. Fatigue and cognitive dysfunction often co-occur in women treated for breast cancer. We hypothesized that pre-treatment factors, unrelated to chemotherapy per se, might increase vulnerability to post-treatment fatigue and cognitive dysfunction. Patients treated with (n = 28) or without chemotherapy (n = 37) and healthy controls (n = 32) were scanned coincident with pre- and one-month post-chemotherapy during a verbal working memory task (VWMT) and assessed for fatigue, worry, and cognitive dysfunction. fMRI activity measures in the frontoparietal executive network were used in multiple linear regression to predict post-treatment fatigue and cognitive function. The chemotherapy group reported greater pre-treatment fatigue than controls and showed compromised neural response, characterized by higher spatial variance in executive network activity, than the non-chemotherapy group. Also, the chemotherapy group reported greater post-treatment fatigue than the other groups. Linear regression indicated that pre-treatment spatial variance in executive network activation predicted post-treatment fatigue severity and cognitive complaints, while treatment group, age, hemoglobin, worry, and mean executive network activity levels did not predict these outcomes. Pre-treatment neural inefficiency (indexed by high spatial variance) in the executive network, which supports attention and working memory, was a better predictor of post-treatment cognitive and fatigue complaints than exposure to chemotherapy per se. This executive network compromise could be a pre-treatment neuromarker of risk, indicating patients most likely to benefit from early intervention for fatigue and cognitive dysfunction.
authors.affiliation: Integrated Brain Imaging Center, Department of Radiology, University of Washington, Seattle, USA, askren@uw.edu.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Askren
authors.forename: Misook
authors.initials: M
authors.lastname: Jung
authors.forename: Marc G
authors.initials: MG
authors.lastname: Berman
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Barbara
authors.initials: B
authors.lastname: Therrien
authors.forename: Scott
authors.initials: S
authors.lastname: Peltier
authors.forename: Lynn
authors.initials: L
authors.lastname: Ossher
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hayes
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Reuter-Lorenz
authors.forename: Bernadine
authors.initials: B
authors.lastname: Cimprich
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced* / Q000175:diagnosis; D005221:Fatigue / Q000139:chemically induced* / Q000175:diagnosis; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008570:Memory, Short-Term / Q000187:drug effects; D008875:Middle Aged; D009483:Neuropsychological Tests; D011446:Prospective Studies
chemical_list: D015415:Biomarkers