title: Neurocognitive function and CNS integrity in adult survivors of childhood hodgkin lymphoma.
abstract: OBJECTIVE
  Long-term survivors of childhood Hodgkin lymphoma (HL) are at risk for cardiopulmonary complications and CNS stroke, although neurocognitive function has not been previously examined. The aim of this study was to examine neurocognitive and brain imaging outcomes in adult survivors of childhood HL.
  
  
  METHODS
  In all, 62 adult survivors (mean age, 42.2 years; standard deviation [SD], 4.77; mean age at diagnosis, 15.1 years; SD, 3.30) were identified by stratified random selection from a large cohort treated with either high-dose (≥ 30 Gy) thoracic radiation (n = 38) or lower-dose (< 30 Gy) thoracic radiation combined with anthracycline (n = 24). Patients underwent neurocognitive evaluations, brain magnetic resonance imaging (MRI), echocardiograms, pulmonary function tests, and physical examinations.
  
  
  RESULTS
  Compared with national age-adjusted norms, HL survivors demonstrated lower performance on sustained attention (P = .004), short-term memory (P = .001), long-term memory (P = .006), working memory (P < .001), naming speed (P < .001), and cognitive fluency (P = .007). MRI revealed leukoencephalopathy in 53% of survivors, and 37% had evidence of cerebrovascular injury. Higher thoracic radiation dose was associated with impaired cardiac diastolic function (E/E'; ratio of peak mitral flow velocity of early rapid filling [E] to early diastolic velocity of the mitral annulus [E']; P = .003), impaired pulmonary function (diffusing capacity of lungs for carbon monoxide [DL(co)(corr); P = .04), and leukoencephalopathy (P = .02). Survivors with leukoencephalopathy demonstrated reduced cognitive fluency (P = .001). Working memory impairment was associated with E/E', although impaired sustained attention and naming speed were associated with DL(co)(corr). Neurocognitive performance was associated with academic and vocational functioning.
  
  
  CONCLUSIONS
  These results suggest that adult long-term survivors of childhood HL are at risk for neurocognitive impairment, which is associated with radiologic indices suggestive of reduced brain integrity and which occurs in the presence of symptoms of cardiopulmonary dysfunction.
authors.affiliation: Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, 262 Danny Thomas Place, MS 735, Memphis, TN 38105-3678, USA. kevin.krull@stjude.org
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Krull
authors.forename: Noah D
authors.initials: ND
authors.lastname: Sabin
authors.forename: Wilburn E
authors.initials: WE
authors.lastname: Reddick
authors.forename: Liang
authors.initials: L
authors.lastname: Zhu
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Armstrong
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Green
authors.forename: Alejandro R
authors.initials: AR
authors.lastname: Arevalo
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Krasin
authors.forename: Deo Kumar
authors.initials: DK
authors.lastname: Srivastava
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Hudson
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D018943:Anthracyclines / Q000009:adverse effects / Q000627:therapeutic use; D002493:Central Nervous System Diseases / Q000209:etiology* / Q000503:physiopathology; D059248:Chemoradiotherapy / Q000009:adverse effects* / Q000379:methods; D002648:Child; D003072:Cognition Disorders / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D006689:Hodgkin Disease / Q000175:diagnosis / Q000523:psychology / Q000628:therapy*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D018570:Risk Assessment; D012737:Sex Factors; D017741:Survivors / Q000523:psychology*; D013997:Time Factors
chemical_list: D018943:Anthracyclines