Dataset Information

Childhood Neurotoxicity and Brain Resilience to Adverse Events during Adulthood.

ABSTRACT:

Objective

This study used childhood cancer survivors as a novel model to study whether children who experience central nervous system (CNS) injury are at higher risk for neurocognitive impairment associated with subsequent late onset chronic health conditions (CHCs).

Methods

Adult survivors of childhood cancer (n = 2,859, ≥10 years from diagnosis, ≥18 years old) completed a comprehensive neurocognitive battery and clinical examination. Neurocognitive impairment was defined as age-adjusted z score < 10th percentile. Participants impaired on ≥3 tests had global impairment. CHCs were graded using the Common Terminology Criteria for Adverse Events v4.3 (grade 1, mild; 2, moderate; 3, severe/disabling; 4, life-threatening) and were combined into a severity/burden score by frequency and grade (none/low, medium, high, and very high). A total of 1,598 survivors received CNS-directed therapy including cranial radiation, intrathecal methotrexate, or neurosurgery. Logistic regression estimated the odds of neurocognitive impairment associated with severity/burden score and grade 2 to 4 conditions, stratified by CNS treatment.

Results

CNS-treated survivors performed worse than non-CNS-treated survivors on all neurocognitive tests and were more likely to have global neurocognitive impairment (46.9% vs 35.3%, p < 0.001). After adjusting for demographic and treatment factors, there was a dose-response association between severity/burden score and global neurocognitive impairment, but only among CNS-treated survivors (high odds ratio [OR] = 2.24, 95% confidence interval [CI] = 1.42-3.53; very high OR = 4.07, 95% CI = 2.30-7.17). Cardiovascular and pulmonary conditions were associated with processing speed, executive function, and memory impairments in CNS-treated but not non-CNS-treated survivors who were impacted by neurologic conditions.

Interpretation

Reduced cognitive/brain reserve associated with CNS-directed therapy during childhood may make survivors vulnerable to adverse cognitive effects of cardiopulmonary conditions during adulthood. ANN NEUROL 2021;89:534-545.

SUBMITTER: Williams AM

PROVIDER: S-EPMC7897299 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Childhood Neurotoxicity and Brain Resilience to Adverse Events during Adulthood.

Williams AnnaLynn M AM Cheung Yin Ting YT Hyun Geehong G Liu Wei W Ness Kirsten K KK Ehrhardt Matthew J MJ Mulrooney Daniel A DA Bhakta Nickhill N Banerjee Pia P Brinkman Tara M TM Green Daniel M DM Chemaitilly Wassim W Huang I-Chan IC Srivastava Deokumar D Hudson Melissa M MM Robison Leslie L LL Krull Kevin R KR

Annals of neurology 20201231 3

<h4>Objective</h4>This study used childhood cancer survivors as a novel model to study whether children who experience central nervous system (CNS) injury are at higher risk for neurocognitive impairment associated with subsequent late onset chronic health conditions (CHCs).<h4>Methods</h4>Adult survivors of childhood cancer (n = 2,859, ≥10 years from diagnosis, ≥18 years old) completed a comprehensive neurocognitive battery and clinical examination. Neurocognitive impairment was defined as age- ...[more]

PMID: 33274777

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Dataset Information

Childhood Neurotoxicity and Brain Resilience to Adverse Events during Adulthood.

Objective

Methods

Results

Interpretation

Publications

Childhood Neurotoxicity and Brain Resilience to Adverse Events during Adulthood.

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