Impact of Taxane Chemotherapy on Gait Performance in Older Women: Does Executive Function Matter?
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ABSTRACT Chemotherapy causes neurotoxic damage to the peripheral (PNS) and central nervous systems (CNS) in older, taxane-treated female breast cancer survivors (OTTBCS). However, the literature has primarily attributed chemotherapy’s significant mobility disability to changes in the PNS through chemotherapy-induced peripheral neuropathy (CIPN) without accounting for the role of the CNS. There is an urgent need to understand the combined contributions of the PNS and CNS to gait in this vulnerable population since the CNS could offer a novel target for rehabilitation. My long-term goal is to become an independent physician scientist who develops mobility interventions tailored for the needs of aging cancer survivors. The proposal’s objectives are to investigate the relationships between measures of CNS function (executive function, prefrontal hemodynamics) and walking performance in OTTBCS and to provide proof-of-concept that transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (dlPFC) can improve walking within this patient population. The central hypothesis is that chemotherapy increases reliance on executive function for walking control by inducing PNS dysfunction, but in these patients the capacity of executive function to compensate may be compromised due to additional CNS damage. Thus, compared to their cancer-free peers, taxane-treated breast cancer survivors will have worse gait performance, particularly while dual task walking (e.g., talking while walking) because of both PNS and CNS dysfunction. The specific aims are to compare OTTBCS to controls in 1) executive function’s role in dual task cost to gait performance, 2) prefrontal cortex activation during dual task walking, and 3) the acute effects of a single exposure to tDCS targeting the left dlPFC on gait performance. In Aims 1 and 2, the study will use a well characterized data set of older, cancer-free women as a control group and compare them to a group of OTTBCS. The NIH cognitive toolbox and dual task walking paradigms recording both gait performance and hemodynamic response via functional near infrared spectroscopy (fNIRS) will be used. For Aim 3, a blinded, randomized, crossover trial will evaluate a single exposure to tDCS to the dlPFC versus sham on dual task gait performance in OTTBCS. The training objectives include developing expertise in 1) study design and analysis, 2) understanding CNS gait control with cognitive tests, fNIRS, and gait assessment, and 3) tDCS neuromodulation. The proposal is significant and innovative, because it will improve the understanding of gait in OTTBCS by moving beyond CIPN to include executive function and the prefrontal cortex and it will assess whether these are modifiable via non- invasive brain stimulation. Ultimately, understanding the contributions of executive function and the prefrontal cortex to gait may impact rehabilitation by adding executive-gait control as a target for mobility interventions.
