Grant Details
Grant Number: |
3U01CA195547-07S1 Interpret this number |
Primary Investigator: |
Hudson, Melissa |
Organization: |
St. Jude Children'S Research Hospital |
Project Title: |
Brain Age in Adult Survivors of Childhood Leukemia and Cns Tumor |
Fiscal Year: |
2021 |
Abstract
Abstract
Long-term survivors of childhood cancer may be at increased risk for accelerated aging and early-onset
dementia, particularly survivors of leukemia and central nervous system (CNS) tumor survivors who are treated
with neurotoxic therapies. We recently demonstrated shorter telomere length in leukemia and CNS tumors more
frequently than community controls and other types of childhood cancer. We have also identified that survivors
of leukemia and CNS tumors are at greatest risk for progressive memory decline during the interval of 25 to 40
years following cancer diagnosis. Adult survivors of childhood leukemia and CNS tumor have lower brain white
and grey matter volume and smaller hippocampi, consistent with a dementia profile. Compared to non-cancer
controls, these survivors demonstrate a lower ratio of hippocampi to cranial vault volume, suggesting loss of
brain tissue volume after peak development of the cranium. This lower ratio is associated with memory problems
and may indicate accelerated brain aging and early onset dementia. CNS-directed cancer treatment at a young
age can limit development of cognitive and brain reserve (i.e., resilience to future brain injury) and reduced
reserve is associated with increased risk for dementia in the general population. However, comprehensive
assessment of brain aging in adult survivors of childhood cancer has not been reported. We propose to calculate
the brain age of a large sample of adult survivors of childhood cancer and community controls. To date, brain
imaging scans have already been collected on 793 adult survivors of childhood leukemia, 197 survivors of CNS
tumor and 250 community controls matched on age, sex and race. We will compare discrepancies between brain
age and chronological age in the survivors and controls and examine associations between brain age
discrepancies with treatment, health, functional status and biomarker measures, including cell free mitochondrial
DNA, collected in the SJLIFE cohort. This will be the first study to directly examine accelerated cognitive and
brain aging in a cohort of adult survivors of childhood cancer treated with neurotoxic therapies as children. These
survivors present with symptoms of memory impairment, consistent with dementia and/or Alzheimer's disease.
The comprehensive longitudinal data available to us will inform dementia onset and progression, as we follow
the survivors in our cohort for the remainder of their life's. Estimates of accelerated brain aging have been shown
to predict dementia and mortality in the general population and thus, this metric may serve as a useful biomarker
for early detection of dementia and/or Alzheimer's disease in cancer survivors. Results of this study will have
major implications for understanding the pathology of dementia and Alzheimer's disease in chronic disease, and
will provide invaluable information concerning risk prediction and intervention development.
Publications
None. See parent grant details.