Research shows that long-term survivors of pediatric Hodgkin lymphoma are at an elevated risk for a variety of health conditions, including cardiopulmonary morbidity, cognitive impairment, and premature death, and could also be at heightened risk for the premature onset of dementia.
A new study of adult survivors of childhood Hodgkin lymphoma by investigators at St. Jude Children’s Research Hospital has found that these survivors experience accelerated cognitive aging and decline that are associated with deficits in visual-motor processing speed, short- and long-term memory, and verbal fluency. Epigenetic age acceleration may be a useful biomarker to identify survivors at risk for the problem and gauge preclinical response to interventions designed to improve cognitive function. The study by Williams et al was presented during the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 902).
Study Methodology
The researchers analyzed data from 215 survivors of pediatric Hodgkin lymphoma. The survivors were 50% female; the mean age was 39 years, and they were a mean of 25 years away from their initial diagnosis. The study also included 282 community controls (51% female, mean age = 36 years) of European ancestry enrolled in the St. Jude Lifetime Cohort Study.
The study participants completed a comprehensive neuropsychological battery of tests and provided a blood sample. Genome-wide methylation data were generated with peripheral blood mononuclear cell-derived DNA using Infinium Methylation EPIC BeadChip arrays. Epigenetic age was calculated using an epigenetic clock to measure biological age; epigenetic age acceleration (EAA) was defined as the residual from regressing the epigenetic age on chronologic age (higher EAA suggested older biological age relative to chronological age). Linear regression, adjusted for sex, compared EAA in the Hodgkin lymphoma survivors and controls, and compared neurocognitive z-score in those in the third or second tertile of EAA to the first tertile, adjusted for sex, age at diagnosis, and previous treatment with high-dose methotrexate.
Results
The researchers found that the Hodgkin lymphoma survivors had significantly greater EAA compared to community controls (P < .001). Among the cancer survivors, EAA was associated with worse visual-motor processing speed, with those in the second tertile performing, on average, 0.42 standard deviations worse (P = .005) and those in the third tertile performing 0.55 standard deviations worse (P < .001) than the Hodgkin lymphoma survivors in the first tertile.
Those in the second and third tertiles also performed worse in terms of short-term memory compared to those in the first tertile. The third tertile of EAA was also associated with worse performance in verbal learning (P = .007) and long-term verbal recall (P = .005). Lastly, those in the second or third tertiles performed 0.4 standard deviations worse, on average, than the first tertile on a measure of executive function (verbal fluency; P = .035 and P = .036, respectively).
“Survivors of pediatric Hodgkin lymphoma experience significant EAA that is associated with deficits in visual-motor processing speed, short- and long-term memory, and verbal fluency. Epigenetic age acceleration may be a useful biomarker to not only identify survivors at risk for accelerated cognitive aging, but also to gauge preclinical response to interventions designed to improve cognitive function,” concluded the study authors.
Disclosure: For full disclosures of the study authors, visit ash.confex.com.
