Assessment of Cerebrovascular Reactivity during Resting State Breathing and Its Correlation with Cognitive Function in Hypertension

Abstract

<b><i>Background:</i></b> Hypertension is associated with cognitive deficits, particularly executive function, and decreased cerebral microvascular responsiveness to CO<sub>2</sub> (CO<sub>2</sub> vasoreactivity). The relation between CO<sub>2</sub> vasoreactivity and executive function is not known. Protocols to assess CO<sub>2</sub> vasoreactivity are cumbersome and require inhaling a CO<sub>2</sub>-enriched gas. We explored the ability to measure CO<sub>2</sub> vasoreactivity using end-tidal CO<sub>2</sub> fluctuations during normal breathing and the association of this measure with cognitive function in hypertension. <b><i>Methods:</i></b> Executive function (Trail-Making Test parts A/B), memory, attention and blood flow velocity (BFV) in the middle cerebral artery using transcranial Doppler were measured in hypertensive subjects who were tapered off their treatment for 3 weeks. BFV was measured while sitting and normally breathing for 5 min, followed by breathing 5% CO<sub>2</sub> gas and hyperventilation for 2 min each. We calculated CO<sub>2</sub> vasoreactivity as the rate of BFV change from hypoventilation to hyperventilation, and as a model-derived measure using the normal breathing data. The latter was derived using nonlinear principal dynamic modes (PDM), which modelled the dynamic effect of fluctuations in end-tidal CO<sub>2</sub> and blood pressure upon BFV during normal room-air respiration. Multiple regression analyses were used to correlate cerebral hemodynamics with cognitive measures. <b><i>Results:</i></b> Data were collected from 41 individuals with hypertension (mean age 71 years, 24% African Americans, 61% women, off antihypertensive therapy). Lower CO<sub>2</sub> vasoreactivity was associated with a worse executive function test score using both calculation methods: p value using the hyper/hypoventilation data was 0.04 and from the PDM analysis was 0.009. PDM calculations showed a stronger correlation with executive function (0.41 vs. 0.21 using the hyper/hypoventilation data). There were no associations with memory or attention measures. There was a weak but statistically significant correlation between the two calculation methods of CO<sub>2</sub> vasoreactivity (R<sup>2</sup> = 14%, p = 0.02). <b><i>Conclusion:</i></b> This study suggests that the decrease in CO<sub>2</sub> vasoreactivity in hypertension is associated with lower executive function. This may offer new insight into the vascular underpinning of cognitive decline in hypertension. We demonstrate that calculating CO<sub>2</sub> vasoreactivity is possible during normal breathing. If replicated in future studies, this may offer a more convenient clinical way to assess CO<sub>2</sub> vasoreactivity in hypertension and cognitive disorders.