Among young adults who survived childhood cancer, those who met criteria for frailty had greater declines in cognitive domains that are associated with dementia and Alzheimer’s disease, according to a study published in the Journal of Clinical Oncology.

Approximately 8% of young adult survivors of childhood cancer meet the criteria for frailty, according to the study authors. This prospective study was intended to characterize the link between frailty and neurocognitive impairment in young adult survivors of childhood cancer.

The study enrolled 845 survivors who were, on average, 29.7 years old and 21.7 years from cancer diagnosis.

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At enrollment, 18.2% of survivors were prefrail, and 6.1% were frail. Patients were categorized as prefrail if they had 2 of the following characteristics and frail if they had 3 or more of the following characteristics: low mean muscle mass, exhaustion, low energy expenditure, slowness, and weakness.

The participants completed neuropsychological assessments at enrollment (January 2008-June 2013) and 5 years later.

When compared with nonfrail survivors, frail survivors had significantly greater declines in the following domains:

  • Short-term verbal recall (b =-.76; 95% CI, -1.19 to -0.33; P =.002)
  • Visual-motor processing speed (b =-.40; 95% CI, -0.67 to -0.12; P =.010)
  • Cognitive flexibility (b =-.62; 95% CI, -1.02 to -0.22; P =.009)
  • Verbal fluency (b =-.23; 95% CI, -0.41 to -0.05; P =.026).

Both prefrail and frail survivors exhibited significantly greater declines in focused attention compared with nonfrail survivors (prefrail, b =-.35; 95% CI, -0.53 to -0.17; P =.001/ frail, b =-.48; 95% CI, -0.83 to -0.12; P =.034).

“Prefrail and frail survivors experienced significant declines in neurocognitive domains commonly associated with dementia and Alzheimer’s disease,” the study authors wrote. “These data suggest interventions that have a global impact, designed to target the mechanistic underpinnings of frailty, may also mitigate or prevent neurocognitive decline.”

Disclosures: This research was supported by the National Cancer Institute and the American Lebanese Syrian Associated Charities. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Williams AM, Krull KR, Howell CR, et al. Physiologic frailty and neurocognitive decline among young-adult childhood cancer survivors: a prospective study from the St Jude Lifetime Cohort. J Clin Oncol. Published online July 20, 2021. doi:10.1200/JCO.21.00194