title: Evaluation of memory impairment in aging adult survivors of childhood acute lymphoblastic leukemia treated with cranial radiotherapy.
abstract: BACKGROUND
  Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood cancer and may increase risk for mild cognitive impairment and dementia in adulthood.
  
  
  METHODS
  We performed a cross-sectional evaluation of survivors of childhood acute lymphoblastic leukemia (ALL) treated with 18 Gy (n = 127) or 24 Gy (n = 138) CRT. Impairment (age-adjusted score >1 standard deviation below expected mean, two-sided exact binomial test) on the Wechsler Memory Scale IV (WMS-IV) was measured. A subset of survivors (n = 85) completed structural and functional neuroimaging.
  
  
  RESULTS
  Survivors who received 24 Gy, but not 18 Gy, CRT had impairment in immediate (impairment rate = 33.8%, 95% confidence interval [CI] = 25.9% to 42.4%; P < .001) and delayed memory (impairment rate = 30.2%, 95% CI = 22.6% to 38.6%; P < .001). The mean score for long-term narrative memory among survivors who received 24 Gy CRT was equivalent to that for individuals older than 69 years. Impaired immediate memory was associated with smaller right (P = .02) and left (P = .008) temporal lobe volumes, and impaired delayed memory was associated with thinner parietal and frontal cortices. Lower hippocampal volumes and increased functional magnetic resonance imaging activation were observed with memory impairment. Reduced cognitive status (Brief Cognitive Status Exam from the WMS-IV) was identified after 24 Gy (18.5%, 95% CI = 12.4% to 26.1%; P < .001), but not 18 Gy (8.7%, 95% CI = 4.4% to 15.0%; P = .11), CRT, suggesting a dose-response effect. Employment rates were equivalent (63.8% for 24 Gy CRT and 63.0% for 18 Gy CRT).
  
  
  CONCLUSIONS
  Adult survivors who received 24 Gy CRT had reduced cognitive status and memory, with reduced integrity in neuroanatomical regions essential in memory formation, consistent with early onset mild cognitive impairment.
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. greg.armstrong@stjude.org
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Armstrong
authors.forename: Wilburn E
authors.initials: WE
authors.lastname: Reddick
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.forename: Aimee
authors.initials: A
authors.lastname: Santucci
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Deokumar
authors.initials: D
authors.lastname: Srivastava
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ogg
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Hillenbrand
authors.forename: Noah
authors.initials: N
authors.lastname: Sabin
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Krasin
authors.forename: Larry
authors.initials: L
authors.lastname: Kun
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Hudson
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Krull
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology*; D002648:Child; D003071:Cognition / Q000528:radiation effects*; D060825:Cognitive Dysfunction / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D003430:Cross-Sectional Studies; D003704:Dementia / Q000175:diagnosis / Q000209:etiology; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D005625:Frontal Lobe / Q000473:pathology; D059907:Functional Neuroimaging; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000528:radiation effects*; D008569:Memory Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D008875:Middle Aged; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000532:radiotherapy*; D011878:Radiotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D017741:Survivors / Q000523:psychology / Q000706:statistics & numerical data; D014481:United States / Q000453:epidemiology