Time-efficient, high-resistance inspiratory muscle strength training increases cerebrovascular reactivity in midlife and older adults.

Aging is associated with increased risk for cognitive decline and dementia due in part to increases in systolic blood pressure (SBP) and cerebrovascular dysfunction. High-resistance inspiratory muscle strength training (IMST) is a time-efficient, intensive respiratory training protocol (30 resisted inspirations/day) that lowers SBP and improves peripheral vascular function in midlife/older adults with above-normal SBP. However, if, and by what mechanisms, IMST can improve cerebrovascular function is unknown. We hypothesized IMST would increase cerebrovascular reactivity to hypercapnia (CVR to CO2 ), which would coincide with changes to the plasma milieu that improve brain endothelial cell function and enhanced cognitive performance (NIH Toolbox). We conducted a 6-week, double-blind, randomized, controlled clinical trial investigating high-resistance IMST (75% maximal inspiratory pressure [PIMAX ]; 6x/week; 4F/5M) vs. low-resistance Sham training (15% PIMAX ; 6x/week; 2F/5M) in midlife/older adults (age 50-79 years) with initial above-normal SBP. Human brain endothelial cells (HBECs) were exposed to participant plasma and assessed for acetylcholine-stimulated nitric oxide (NO) production. CVR to CO2 increased after high-resistance IMST (pre: 1.38±0.66 cm/s/mmHg, post: 2.31±1.02 cm/s/mmHg, p=0.020). Acetylcholine-stimulated NO production increased in HBECs exposed to plasma from after vs. before the IMST intervention (pre: 1.49±0.33 au, post: 1.73±0.35 au; p<0.001). Episodic memory increased modestly after the IMST intervention (pre: 95±13 au, post: 103±17 au; p=0.045). Cerebrovascular and cognitive function were unchanged in the Sham control group. High-resistance IMST may be a promising strategy to improve cerebrovascular and cognitive function in midlife/older adults with above-normal SBP, a population at risk for future cognitive decline and dementia.