Association Between Frailty and Cognitive Decline Noted in Young-Adult Cancer Survivors


Young-adult cancer survivors who met criteria for being prefrail and frail were more likely to experience a cognitive decline compared with those considered to be nonfrail.

Meeting criteria for being prefrail and frail compared with nonfrail in young adults who were cancer survivors was associated with greater decline in cognitive domains that are associated with aging and dementia, according to a study published in the Journal of Clinical Oncology.

Patients who were frail had declines in short term recall (standard deviation [SD], 0.54; 95% CI, –0.93 to –0.15) whereas nonfrail survivors did not (β, .22; difference of β, –.76; 95% CI, –1.19 to –0.33).

“This prospective study of clinically evaluated survivors of childhood cancer provides novel data demonstrating that physiologic frailty is associated both cross-sectionally with neurocognitive impairment and longitudinally with neurocognitive decline in young-adult survivors of childhood cancer,” wrote the study investigators who were led by AnnLynn M. Williams, PhD.

This analysis included 845 survivors who were an average of 29.7 years old and 21.7 years from diagnosis. Patients who were eligible for the study were more frequently White and had a higher-than-average rate of treatment exposures directed at the central nervous system. At enrollment, 6.1% were considered prefrail and 18.2% were frail. From enrollment to follow-up, 70.9% of patients did not change frailty status; however, 17.6% of patients worsened, and 11.5% improved in frailty status from enrollment to follow-up.

Regardless of frailty status, patients in this sample performed worse on neurocognitive assessments compared with population norms. Patients who were prefrail and frail had higher neurocognitive impairment such as attention variability, processing speed, motor processing speed, verbal learning, short- and long-term recall, cognitive flexibility, and verbal fluency compared with those who were nonfrail.

Decline in short-term recall was 0.76 SD greater in frail versus nonfrail patients (P-adjusted = .002). Decline in attention variability in frail survivors (SD, 0.41; 95% CI, –0.70 to –0.12) was greater than nonfrail survivors, but was not significant after adjusting for multiple testing (β, –.33; 95% CI, –0.63 to –0.02; P-adjusted = .079). Declines in visual-motor processing speed (SD, 0.21; 95% CI, -0.46 to 0.05), cognitive flexibility (SD, 0.13; 95% CI, –0.52 to –0.26), and verbal fluency (SD, 0.11; 95% CI, –0.28 to 0.06) were also noted for frail survivors and all of these declines were greater than those seen among nonfrail survivors.

Decline on focused attention was statistically significant among prefrail (β = –.35; 95% CI, –0.53 to –0.17, P-adjusted = .001) and frail (β = –.48; 95% CI, –0.83 to –0.12, P-adjusted = .034) compared with nonfrail survivors.

Investigators used a sensitivity analysis that had a 9-level frailty variable that allowed for every combination of status at enrollment and follow-up. This analysis showed similar results for prefrail and frail focused attention and verbal fluency. In those who received central nervous system–directed therapy, there were associations found between frailty level and decline in visual motor processing speed, short-term verbal recall, cognitive flexibility, and verbal fluency that were similar to primary findings, with the exception of short-term recall.

Investigators also found associations between individual frailty and neurocognitive decline. Additionally, impaired grip strength was associated with declines in each domain, while declines in visual-motor processing speed, short-term recall, and verbal fluency were associated with exhaustion and slow walking speed.

“This decline was much larger than that seen among nonfrail survivors and is considered clinically meaningful given the short time frame and young age of the [St. Jude Lifetime Cohort] SJLIFE survivor population (mean age 29 years). Childhood cancer survivors experience rates of frailty similar to those 3 decades older, consistent with an accelerated aging phenotype and biomarkers of aging,” concluded investigators.


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

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