BACKGROUND: Gait impairments present while dual-tasking in older adults with multiple sclerosis (MS) have been associated with an increased risk of falls. Prior studies have examined prefrontal cortex (PFC) activity using functional near infrared spectroscopy (fNIRS) while dual-tasking in older adults with and without cognitive impairment. While the benefits of partial body weight support (PBWS) on gait have been clearly outlined in the literature, the potential use of PBWS to improve the ability to dual task in older adults with and without MS has not been examined. The aim of this study was to examine the effects of PBWS on the PFC activation while dual-tasking in older adults with and without MS. METHODS: Ten individuals with MS (mean 56.2 ± 5.1 yrs., 8 females) and 12 healthy older adults (HOA) (mean 63.1 ± 4.4 yrs., 9 females) participated in this study. PFC activation (i.e., oxygenated hemoglobin-HbO) was measured using fNIRS. Assessments were done under two treadmill walking conditions: no body weight support (NBWS) and PBWS. Under each condition, participants were asked to walk at a comfortable speed (W) or walk and talk (WT). Linear mixed models were used to test for differences between cohorts, conditions, and tasks. RESULTS: HbO levels differed significantly between task (p < .001), cohort (p < .001), and BWS (p = .02). HbO levels increased under higher cognitive demands (i.e., W vs WT), in individuals with MS, and under different conditions (i.e., NBWS vs PBWS). Post-hoc analysis demonstrated a significant difference between cohorts during the WT and NBWS condition (p = .05). When examining the relative change in HbO levels during each task, a significant interaction between task, BWS, and cohort across time was observed (p < 0.01). While HOA increased PFC activation across time, MS exhibited a maintenance of PFC activation patterns during the WT under PBWS condition. CONCLUSIONS: This study establishes the potential impact of PBWS on PFC activation patterns under dual-tasking conditions and sheds light on the ability for PBWS to be used as a therapeutic tool in individuals with neurological conditions to decrease cognitive demands while dual-tasking and thus decrease the risk of falls.