The incidence of chemotherapy-related cognitive impairment (CRCI) is approximately 60% but its etiology remains unclear. There is significant overlap between chemotherapy actions and physiologic processes involved in Alzheimer?s Disease (AD)-related neurodegeneration. AD and CRCI share a genetic risk (i.e. APOE e4 genotype) and previous studies suggest that chemotherapy may accelerate the aging processes. We have consistently shown that patients with CRCI have lower brain network (?connectome?) organization. We also have preliminary evidence that chemotherapy-treated patients with a certain profile of connectome organization have higher predicted probability of Alzheimer?s Disease and its related dementias (AD/ADRD) even after controlling for apolipoprotein (APOE) genotype. It is also unknown what molecular mechanisms might contribute to this increased AD probability. Major neurodegenerative processes in AD include amyloid-beta accumulation, tau hyperphosphorylation and inflammation. CRCI has been associated with chronically elevated pro-inflammatory cytokines but few studies have evaluated cytokine levels longitudinally and none have examined the contribution of tau, amyloid-beta or their interaction with cytokine elevation in CRCI. Our preliminary work suggests peripheral tau elevation associated with CRCI. We have already collected the fMRI, medical and self-report data from our cohort of 105 participants (35 cancer patients who underwent chemotherapy treatment, 35 cancer patients who did not receive chemotherapy and 35 healthy controls) pre, post and 1 year after cancer treatments (or relevant yoked intervals). Our newly funded renewal R01 offers a unique opportunity to collect further longitudinal data on this cohort as they reach very long-term survivorship (up to 10+ years post- treatment) and begin to reach advanced age when pathologic neurodegeneration becomes more likely. This supplement will allow us address several important questions directly relevant to ADRD and will likely stimulate additional activity leading to progress on ADRD by examining longitudinal predicted probability of ADRD from pre-treatment to up to 10+ years post-treatment. Additionally, we will be able to examine the effects of chemotherapy on biomarkers of AD- related neurodegeneration.
. Alzheimer?s Disease (AD) is prevalent and degenerative disease without known treatment or prevention strategy. Chemotherapy causes cancer related cognitive impairment (CRCI). CRCI and AD share common brain network organization and biomarkers. Therefore, examining the effects of chemotherapy on mechanisms involved in AD might provide unique insights regarding the etiology of CRCI and further our understanding of AD.
|Henneghan, Ashley M; Palesh, Oxana; Harrison, Michelle et al. (2018) Identifying cytokine predictors of cognitive functioning in breast cancer survivors up to 10?years post chemotherapy using machine learning. J Neuroimmunol 320:38-47|
|Kesler, Shelli R; Adams, Marjorie; Packer, Melissa et al. (2017) Disrupted brain network functional dynamics and hyper-correlation of structural and functional connectome topology in patients with breast cancer prior to treatment. Brain Behav 7:e00643|
|Kesler, Shelli R; Noll, Kyle; Cahill, Daniel P et al. (2017) The effect of IDH1 mutation on the structural connectome in malignant astrocytoma. J Neurooncol 131:565-574|
|Kesler, Shelli R; Rao, Arvind; Blayney, Douglas W et al. (2017) Predicting Long-Term Cognitive Outcome Following Breast Cancer with Pre-Treatment Resting State fMRI and Random Forest Machine Learning. Front Hum Neurosci 11:555|
|Kesler, Shelli R; Rao, Vikram; Ray, William J et al. (2017) Probability of Alzheimer's disease in breast cancer survivors based on gray-matter structural network efficiency. Alzheimers Dement (Amst) 9:67-75|
|Hosseini, S M Hadi; Pritchard-Berman, Mika; Sosa, Natasha et al. (2016) Task-based neurofeedback training: A novel approach toward training executive functions. Neuroimage 134:153-159|
|Kesler, Shelli R; Blayney, Douglas W (2016) Neurotoxic Effects of Anthracycline- vs Nonanthracycline-Based Chemotherapy on Cognition in Breast Cancer Survivors. JAMA Oncol 2:185-92|
|Saggar, Manish; Hosseini, S M Hadi; Bruno, Jennifer L et al. (2015) Estimating individual contribution from group-based structural correlation networks. Neuroimage 120:274-84|
|Kesler, Shelli R; Watson, Christa L; Blayney, Douglas W (2015) Brain network alterations and vulnerability to simulated neurodegeneration in breast cancer. Neurobiol Aging 36:2429-42|
|Wefel, Jeffrey S; Kesler, Shelli R; Noll, Kyle R et al. (2015) Clinical characteristics, pathophysiology, and management of noncentral nervous system cancer-related cognitive impairment in adults. CA Cancer J Clin 65:123-38|
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