title: Uric Acid and Neurocognitive Function in Survivors of Childhood Acute Lymphoblastic Leukemia Treated with Chemotherapy Only.
abstract: Hyperuricemia is implicated in cardiovascular and cerebrovascular diseases. This study evaluated associations between uric acid (UA), cardiovascular health, and neurocognitive function in adolescent and adult survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only.
  
  
  
  126 adolescent [mean (SD) age 14.6 (5.0); 7.8 (1.7) years postdiagnosis] and 226 adult survivors [age 25.4 (4.2) years; 18.1 (4.4) years postdiagnosis] completed comprehensive neurocognitive testing. Concurrent UA measurements were conducted for both groups. For adult survivors, cardiovascular risk factors were assessed, and UA measurements during adolescence [12.3 (4.0) years before neurocognitive testing] were also collected. UA levels were categorized into quartiles for age- and gender-based ranking, and associations with neurocognitive outcomes were examined.
  
  
  
  Survivors demonstrated worse attention, processing speed, and executive functions than population norms (P values < 0.05). Adolescent survivors with elevated UA had poorer attention (P = 0.04), visual-processing speed (P = 0.03), and cognitive flexibility (P = 0.02). UA was not associated with neurocognitive outcomes in adult survivors. Adult survivors developed dyslipidemia (46%), hypertension (32%), and abdominal obesity (26%), and high UA during adolescence was associated with these cardiovascular risk factors as adults (all P values < 0.01). Fine-motor processing speed was slower in adult survivors with dyslipidemia (P = 0.04) and abdominal obesity (P = 0.04). Poorer attention was marginally associated with hypertension (P = 0.06).
  
  
  
  Elevated UA is associated with neurocognitive performance in adolescent survivors. In adult survivors, relative elevation of UA during adolescence was predictive of cardiovascular health, which was associated with poorer neurocognitive outcomes.
  
  
  
  Future studies should evaluate the mediating role of chronic cardiovascular health conditions between elevated UA and subsequent neurocognitive impairment in survivors. Cancer Epidemiol Biomarkers Prev; 25(8); 1259-67. ©2016 AACR.
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Yin Ting
authors.initials: YT
authors.lastname: Cheung
authors.affiliation: Department of Psychology, University of Denver, Denver, Colorado.
authors.forename: Michelle N
authors.initials: MN
authors.lastname: Edelmann
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Mulrooney
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Green
authors.affiliation: Department of Endocrinology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Wassim
authors.initials: W
authors.lastname: Chemaitilly
authors.affiliation: University of Alabama, Birmingham, Alabama.
authors.forename: Neena
authors.initials: N
authors.lastname: John
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Hudson
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee. Department of Psychology, St. Jude Children's Research Hospital, Memphis, Tennessee. kevin.krull@stjude.org.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Krull
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D000073116:Cancer Survivors / Q000523:psychology / Q000706:statistics & numerical data; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000453:epidemiology; D003072:Cognition Disorders / Q000453:epidemiology* / Q000209:etiology; D015331:Cohort Studies; D050171:Dyslipidemias / Q000139:chemically induced; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D009483:Neuropsychological Tests; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D014527:Uric Acid