title: Cerebral hyporesponsiveness and cognitive impairment 10 years after chemotherapy for breast cancer.
abstract: Chemotherapy is associated with cognitive impairment in a subgroup of breast cancer survivors, but the neural circuitry underlying this side effect is largely unknown. Moreover, long-term impairment has not been studied well. In the present study, functional magnetic resonance imaging (fMRI) and neuropsychological testing were performed in breast cancer survivors almost 10 years after high-dose adjuvant chemotherapy (chemo group, n = 19) and in breast cancer survivors for whom chemotherapy had not been indicated (control group, n = 15). BOLD activation and performance were measured during an executive function task involving planning abilities (Tower of London) and a paired associates task for assessment of episodic memory. For the chemo group versus the control group, we found hyporesponsiveness of dorsolateral prefrontal cortex in the Tower of London, and of parahippocampal gyrus in the paired associates task. Also, the chemo group showed significantly impaired planning performance and borderline significantly impaired recognition memory as compared to findings in the control group. Whole-brain analyses demonstrated hyporesponsiveness of the chemo versus the control group in very similar regions of bilateral posterior parietal cortex during both the Tower of London and the paired associates task. Neuropsychological testing showed a relatively stable pattern of cognitive impairment in the chemo group over time. These results indicate that high-dose adjuvant chemotherapy is associated with long-term cognitive impairments. These impairments are underpinned by (a) task-specific hyporesponsiveness of dorsolateral prefrontal cortex and parahippocampal gyrus, and (b) a generalized hyporesponsiveness of lateral posterior parietal cortex encompassing attentional processing.
authors.affiliation: Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, The Netherlands. mbderuiter@gmail.com
authors.forename: Michiel B
authors.initials: MB
authors.lastname: de Ruiter
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Reneman
authors.forename: Willem
authors.initials: W
authors.lastname: Boogerd
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.forename: Frits S A M
authors.initials: FS
authors.lastname: van Dam
authors.forename: Aart J
authors.initials: AJ
authors.lastname: Nederveen
authors.forename: Epie
authors.initials: E
authors.lastname: Boven
authors.forename: Sanne B
authors.initials: SB
authors.lastname: Schagen
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects*; D001931:Brain Mapping; D001943:Breast Neoplasms / Q000188:drug therapy*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced*; D016208:Databases, Factual; D056344:Executive Function / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D011939:Mental Recall / Q000187:drug effects; D008875:Middle Aged; D009483:Neuropsychological Tests
chemical_list: D000970:Antineoplastic Agents