Using neurocognitive phenotypes to inform interventions for adult survivors of childhood cancer

Author:

Banerjee Pia1,Phillips Nicholas S2ORCID,Liu Wei3,Ehrhardt Matthew J14,Bhakta Nickhill15,Brinkman Tara M12,Williams Annalynn M1,Yasui Yutaka1ORCID,Khan Raja B6,Srivastava Deokumar3,Ness Kirsten K1,Robison Leslie L1,Hudson Melissa M14,Krull Kevin R2

Affiliation:

1. Department of Epidemiology and Cancer Control, St Jude Children’s Research Hospital , Memphis, TN, USA

2. Department of Psychology and Biobehavioral Science, St Jude Children’s Research Hospital , Memphis, TN, USA

3. Department of Biostatistics, St Jude Children’s Research Hospital , Memphis, TN, USA

4. Department of Oncology, St Jude Children’s Research Hospital , Memphis, TN, USA

5. Department of Global Pediatric Medicine, St Jude Children’s Research Hospital , Memphis, TN, USA

6. Department of Pediatric Medicine, Division of Neurology, St Jude Children’s Research Hospital , Memphis, TN, USA

Abstract

Abstract Background Neurocognitive impairments are sequelae of childhood cancer treatment, however little guidance is given to clinicians on common phenotypes of impairment or modifiable risk factors that could lead to personalized interventions in survivorship. Methods Standardized clinical testing of neurocognitive function was conducted in 2958 (74.1%) eligible survivors, who were at least 5 years postdiagnosis and aged older than 18 years, and 477 community controls. Impairment was examined across 20 measures, and phenotypes were determined by latent class analysis. Multinomial logistic regression was used to estimate risk for phenotype, predicted by cancer diagnosis and treatment exposures, chronic health conditions, and lifestyle, adjusted for sex and age. Associations between phenotypes and social attainment were examined. Results Five neurocognitive phenotypes were identified in survivors (global impairment 3.7%, impaired attention 5.0%, memory impairment 7.2%, processing speed and executive function impairment 9.3%, no impairment 74.8%). Risk of global impairment was associated with severe chronic health condition burden (odds ratio [OR] = 20.17, 95% confidence interval [CI] = 11.41 to 35.63) including cerebrovascular disease (OR = 14.5, 95% CI = 5.47 to 38.44) and cerebrovascular accident (OR = 14.7, 95% CI = 7.50 to 26.40). Modifiable risk factors, such as quitting smoking, reduced risk for global impairment (OR = 0.21, 95% CI = 0.06 to 0.66). Low physical activity increased risk for global impairment (OR = 4.54, 95% CI = 2.86 to 7.21), attention impairment (OR = 2.01, 95% CI = 1.41 to 2.87), processing speed and executive function impairment (OR = 1.90, 95% CI = 1.46 to 2.48), and memory impairment (OR = 2.09, 95% CI = 1.54 to 2.82). Conclusions Results support the clinical utility of neurocognitive phenotyping to develop risk profiles and personalized clinical interventions, such as preventing cerebrovascular disease in anthracycline-treated survivors by preventing hypercholesterolemia, smoking, and sedentary lifestyle, to reduce the risk for global impairment.

Funder

National Cancer Institute

Publisher

Oxford University Press (OUP)

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