In a prospective study from the St. Jude Lifetime Cohort reported in the Journal of Clinical Oncology, Williams et al found that prefrailty and frailty among young adult childhood cancer survivors were associated with neurocognitive decline vs nonfrail counterparts, mirroring the association between frailty and neurocognitive decline in the elderly general population.
Study Details
In the study, childhood cancer survivors aged 18 to 45 years and 10 or more years from diagnosis were assessed for prefrailty or frailty, respectively defined as at least two or at least three of the following criteria:
- Muscle wasting
- Muscle weakness
- Low energy expenditure
- Slow walking speed
- Exhaustion (Fried criteria)
- Completed neurocognitive assessments at enrollment (January 2008–June 2013) and 5 years later.
Differences in neurocognitive decline in prefrail and frail vs nonfrail survivors were compared using weighted linear regression with inverse of sampling probability estimates as weights; analyses were adjusted for diagnosis age, sex, race, central nervous system–directed therapy, and baseline neurocognitive performance.
Key Findings
A total of 845 survivors who completed both enrollment and follow-up neurocognitive examination were included in analyses. Of these, 6.1% and 18.2% were frail and prefrail, respectively, at enrollment. The average age was 29.7 years, and the average time from diagnosis was 21.7 years.
Over approximately 5 years, prefrail and frail young adult survivors had greater declines in cognitive domains associated with aging and dementia compared with nonfrail survivors.— Williams et al
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Compared with nonfrail survivors, those with frailty had significant declines in short-term recall (0.76 standard deviation difference; β = −0.76, adjusted P = .002), visual-motor processing speed (β = −0.40, P = .010), cognitive flexibility (β = −0.62, P = .009), focused attention (β = −0.48, P = .034), and verbal fluency (β = −0.23, P = .026). A decline in attention variability was also observed but was no longer significant after adjustment for multiple comparisons (β = −0.33, P = .079). Comparative numeric declines were observed for: verbal and nonverbal reasoning; word reading and mathematics; sustained attention; motor processing speed; verbal learning and long-term verbal recall; and perseveration and working memory (executive function domain).
Compared with nonfrail survivors, those with prefrailty had a significant decline in focused attention (β = −0.35, P = .001). Comparative numeric declines were observed for: verbal and nonverbal reasoning; word reading; commissions (attention domain); visual-motor and motor processing speed; short-term memory, verbal learning, and short- and long-term verbal recall; and working memory, cognitive flexibility, and verbal fluency (executive function domain).
The investigators concluded, “Over approximately 5 years, prefrail and frail young adult survivors had greater declines in cognitive domains associated with aging and dementia compared with nonfrail survivors. Interventions that have global impact, designed to target the mechanistic underpinnings of frailty, may also mitigate or prevent neurocognitive decline.”
Kirsten K. Ness, PhD, PT, of the Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by National Cancer Institute grants and the American Lebanese Syrian Associated Charities. For full disclosures of the study authors, visit ascopubs.org.
