title: Radiotherapeutic effects on brain function: double dissociation of memory systems.
abstract: OBJECTIVE
  The neurocognitive sequelae of therapeutic cranial irradiation are not well characterized in adults with primary brain tumors. To address this problem, we prospectively examined neuropsychological findings during two phases of radiation effects.
  
  
  BACKGROUND
  Investigations of radiation effects have revealed variable outcomes that range from no radiation-associated morbidity to severe cognitive impairment, but have relied on case reports or retrospective studies of late-delayed changes in white matter or in cognition. No reliable radiographic or neurocognitive tools exist to describe the multiple phases of radiation effects.
  
  
  METHODS
  Twenty adult patients (median age, 39 years) from a university hospital were treated with radiotherapy (RT) for low-grade primary brain tumors. Prospective longitudinal neuropsychological studies were compared at baseline (after surgery and before irradiation) and at 3, 6, and 12 months after RT to examine early-delayed effects, including verbal memory changes in 20 patients and visual memory changes in 11 patients. We also examined cognitive changes during the late-delayed phase for up to 3 years after RT and determined whether early-delayed memory deficit predicted late-delayed memory deficit in a small subset of patients. A comprehensive neuropsychological battery was used, including verbal and visual memory tests designed to compare learning, storage, and retrieval.
  
  
  RESULTS
  Patients demonstrated normal verbal memory at baseline, decrement, and then rebound in verbal retrieval. Deficit at baseline and recovery up to 1 year after RT defined visual memory. Together, these observations constitute a double dissociation of memory functions. No changes over time were observed in other neurocognitive tests or in fatigue or mood measures. Time-dependent patterns of each long-term memory test were examined in relation to lesion site in individual patients.
  
  
  CONCLUSIONS
  The double dissociation of memory functions after RT may provide markers for the damaging and facilitative early-delayed effects of RT. Late-delayed effects were not predicted based on early-delayed changes in a small sample.
authors.affiliation: Department of Neurology, University of Pennsylvania Medical School and Children's Hospital of Philadelphia, 19104-4399, USA. armstrong@email.chop.edu
authors.forename: C L
authors.initials: CL
authors.lastname: Armstrong
authors.forename: B W
authors.initials: BW
authors.lastname: Corn
authors.forename: J E
authors.initials: JE
authors.lastname: Ruffer
authors.forename: A A
authors.initials: AA
authors.lastname: Pruitt
authors.forename: J E
authors.initials: JE
authors.lastname: Mollman
authors.forename: P C
authors.initials: PC
authors.lastname: Phillips
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000503:physiopathology / Q000528:radiation effects*; D001932:Brain Neoplasms / Q000532:radiotherapy*; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D005500:Follow-Up Studies; D005556:Form Perception / Q000502:physiology; D006801:Humans; D008569:Memory Disorders / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data*; D011446:Prospective Studies; D011878:Radiotherapy / Q000009:adverse effects*; D012660:Semantics; D014706:Verbal Learning / Q000502:physiology