Acute lymphoblastic leukemia (ALL) is one of the most frequent types of cancer in children. Although childhood ALL is typically curable, the chemotherapeutic agents used in most treatment regimens are neurotoxic, and between 40-70% of children treated for ALL exhibit measurable deficits in cognitive functioning. However, the specific processing deficits contributing to poor cognitive functioning in survivors of childhood ALL and the implications for ongoing brain development are poorly understood. 

We use a combination of behavioral, electrophysiological, and neuroimaging measures to demonstrate the impact on neurocognitive function, brain activity, and brain development following chemotherapy compared to healthy, matched controls. A preliminary study in our lab indicated deficiencies in all cognitive domains for survivors compared to age-matched controls (Brace et al. 2019). We are further investigating treatment-related effects on brain functions, identifying abnormal patterns of neural connectivity, and assessing the chronic effects of chemotherapy treatment on the development of cognitive skills in childhood survivors. Defining the loci of neurocognitive dysfunction caused by ALL treatment will guide the development of novel preventive, treatment, and intervention strategies.

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Related papers: Brace, K.M., Lee, W.W., Cole, P.D., & Sussman E.S. (2019). Childhood leukemia survivors exhibit deficiencies in sensory and cognitive processes, as reflected by event-related brain potentials after completion of curative chemotherapy: A preliminary investigation. Journal of Clinical and Experimental Neuropsychology, 41(8):814-831. doi: 10.1080/13803395.2019.1623865. PMID: 31156064. (Brace et al. 2019).

Cole PD, Vijayanathan V, Ali NF, Wagshul ME, Tanenbaum EJ, Price J, Dalal V, Gulinello ME. Memantine protects rats treated with intrathecal methotrexate from developing spatial memory deficits. Clin Cancer Res. 2013 Aug 15;19(16):4446-54. doi: 10.1158/1078-0432.CCR-13-1179. (Cole et al. 2013).

https://montefioreeinstein.org/nih-grant-to-fund-study-of-chemo-brain-among-children

https://www.healthimaging.com/topics/healthcare-economics/nih-46m-chemo-brain-children

https://www.prnewswire.com/news-releases/understanding-chemo-brain-in-children-researchers-secure-4-6-million-nih-grant-to-identify-those-at-risk-301110097.html

Androgen deprivation therapy (ADT) is a hormone treatment for prostate cancer that reduces testosterone levels to slow tumor growth. However, it is theorized that treatment sometimes has the side effect of diminishing cognitive ability. 

In our lab, we are using advanced brain imaging techniques to identify which cognitive abilities are most affected, in which individuals, and which specific brain regions or pathways are affected by ADT therapy. Our collaborators in Dr. Tiago Goncalves’ lab are uncovering the mechanisms responsible for these changes in an animal model and testing intervention therapies that will lead to future clinical trials in humans. 

The longer-term goal of our work is to help guide survivorship care by developing neurocognitive assessments and by making remedial interventions possible. Our results will also increase our understanding of the effects on brain functions associated with ADT therapy and facilitate our ability to make appropriate recommendations for improving cognition after therapy has ended.