title: Longitudinal assessment of chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning.
abstract: OBJECTIVE
  To uncover the neural substrate of cognitive impairment related to adjuvant chemotherapy, we studied cerebral white matter (WM) integrity before and after chemotherapy by using magnetic resonance diffusion tensor imaging (DTI) in combination with detailed cognitive assessment.
  
  
  METHODS
  Thirty-four young premenopausal women with early-stage breast cancer who were exposed to chemotherapy underwent neuropsychologic testing and DTI before the start of chemotherapy (t1) and 3 to 4 months after treatment (t2). Sixteen patients not exposed to chemotherapy and 19 age-matched healthy controls underwent the same assessment at matched intervals. In all groups, we used paired t tests to study changes in neuropsychologic test scores and whole-brain voxel-based paired t tests to study changes in WM fractional anisotropy (FA; a DTI measure that reflects WM tissue organization), with depression scores and intelligence quotient as included covariates. We correlated changes of neuropsychologic test scores with the mean change of FA for regions that survived the paired t tests in patients treated with chemotherapy.
  
  
  RESULTS
  In contrast to controls, the chemotherapy-treated group performed significantly worse on attention tests, psychomotor speed, and memory at t2 compared with t1 (P < .05). In the chemotherapy-treated group, we found significant decreases of FA in frontal, parietal, and occipital WM tracts after treatment (familywise error P < .05), whereas for both control groups, FA values were the same between t1 and t2. Furthermore, performance changes in attention and verbal memory correlated with mean regional FA changes in chemotherapy-treated patients (P < .05).
  
  
  CONCLUSIONS
  We report evidence of longitudinal changes in cognitive functioning and cerebral WM integrity after chemotherapy as well as an association between both.
authors.affiliation: University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Herestraat 49, B-3000 Leuven, Belgium.
authors.forename: Sabine
authors.initials: S
authors.lastname: Deprez
authors.forename: Frederic
authors.initials: F
authors.lastname: Amant
authors.forename: Ann
authors.initials: A
authors.lastname: Smeets
authors.forename: Ronald
authors.initials: R
authors.lastname: Peeters
authors.forename: Alexander
authors.initials: A
authors.lastname: Leemans
authors.forename: Wim
authors.initials: W
authors.lastname: Van Hecke
authors.forename: Judith S
authors.initials: JS
authors.lastname: Verhoeven
authors.forename: Marie-Rose
authors.initials: MR
authors.lastname: Christiaens
authors.forename: Joris
authors.initials: J
authors.lastname: Vandenberghe
authors.forename: Mathieu
authors.initials: M
authors.lastname: Vandenbulcke
authors.forename: Stefan
authors.initials: S
authors.lastname: Sunaert
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003072:Cognition Disorders / Q000139:chemically induced* / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009483:Neuropsychological Tests
chemical_list: D000970:Antineoplastic Agents