Abstract Age is the major risk factor for AD, which affects ~5.8 million Americans. Increasing physical activity (PA) could decrease the prevalence of Alzheimer’s Disease (AD) and AD Related Dementias by 11%. Yet, the majority of older adults (54%) remain physically inactive. Traditional PA interventions do not reduce excessive sitting in older adults. In particular, sitting continuously for 20 min or longer (i.e., prolonged sitting) can acutely reduce frontoparietal brain function and attentional control. Thus, habitually high levels of prolonged sitting in older adults (5 h/day) may contribute to the declining efficiency of the frontoparietal brain function with age, negatively affecting attentional control and consolidation of episodic memories. Accordingly, PA interventions to enhance frontoparietal and cognitive function in older adults should also target reducing prolonged sitting. However, no effective PA interventions designed to reduce prolonged sitting and improve frontoparietal brain function, attentional control, and episodic memory exist. To be effective such interventions should target the mechanisms underlying PA effects on brain function. A single bout of PA is thought to enhance frontoparietal brain function by stimulating phasic release of cerebral norepinephrine from the locus coeruleus. Specifically, PA stimulates vagus nerve in the periphery by increasing levels of peripheral catecholamines. Capitalizing on PA intensity as the major limiting factor in peripheral catecholamine increase, we propose a pilot randomized crossover feasibility trial to compare 2 conditions lasting 3.5 h each: sitting interrupted by 6-min HIIT every 30 min (HIIT Breaks), and sitting interrupted by 6-min social interactions (SIT) to address 3 aims: (i) to assess feasibility, acceptability, fidelity, and safety of HIIT Breaks to improve neurocognitive function; (ii) to quantify the differences between conditions in the change in P3b amplitude and latency; (iii) to explore the differences between conditions in attentional control, episodic memory, and functional connectivity (FC) of the frontoparietal and default mode networks. We will administer the conditions in a counterbalanced order to 54 older adults (60-75 years). We will use the P3b component of an event-related potential as a primary outcome because it is a known marker of frontoparietal brain function, and an index of phasic shifts (e.g., in response to PA) in cerebral norepinephrine release. It is also reliably modulated by exercise. Next, we will measure FC in the frontoparietal and default mode brain networks because they are modulated by cerebral norepinephrine, and support attentional control and episodic memory, respectively. Furthermore, FC in these networks can be improved with a single bout of PA but declines with age. These results will reveal if short bouts of HIIT can be used as a model to regularly enhance brain function and cognition, by probing cerebral norepinephrine release in...