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

Abstract

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, whether, and by what mechanisms, IMST can improve cerebrovascular function is unknown. We hypothesized that 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 enhance cognitive performance (NIH Toolbox). We conducted a 6-wk double-blind, randomized, controlled clinical trial investigating high-resistance IMST [75% maximal inspiratory pressure (PI_max); 6×/wk; 4 females, 5 males] vs. low-resistance sham training (15% PI_max; 6×/wk; 2 females, 5 males) in midlife/older adults (age 50-79 yr) 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; post: 1.73 ± 0.35 arbitrary units (AU); P < 0.001]. Episodic memory increased modestly after the IMST intervention (pre: 95 ± 13; 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.NEW & NOTEWORTHY Midlife/older adults with above-normal blood pressure are at increased risk of developing cognitive decline and dementia. Our findings suggest that high-resistance inspiratory muscle strength training (IMST), a novel, time-efficient (5-10 min/day) form of physical training, may increase cerebrovascular reactivity to CO₂ and episodic memory in midlife/older adults with initial above-normal blood pressure.

Keywords: cerebrovasculature; cognitive function; exercise training; nitric oxide.

Graphical abstract

Figure 1.

A and B: cerebrovascular reactivity to hypercapnia (CVR to CO₂; A) and cerebrovascular conductance index reactivity (CVCiR; B) to hypercapnia before and after 6 wk of low-resistance sham training (n = 7) or high-resistance inspiratory muscle strength training (IMST) (n = 9). C: fold change in acetylcholine (ACh)-stimulated nitric oxide (NO) production of cultured human brain endothelial cells exposed to plasma obtained from participants before and after 6 wk of low-resistance sham training (n = 7) or high-resistance IMST (n = 8). Each plasma sample was tested using 3 experimental replicates and averaged. Dark gray circles indicate individual data at baseline, and gold circles indicate individual data at posttesting. Statistics are 2-way repeated-measures ANOVA with Fisher’s least significant difference post hoc analysis.