Uric Acid and Neurocognitive Function in Survivors of Childhood Acute Lymphoblastic Leukemia Treated with Chemotherapy Only.

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Impact: 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.