Assessment of cerebrovascular reactivity during resting state breathing and its correlation with cognitive function in hypertension.

Background: Hypertension is associated with cognitive deficits, particularly executive function, and decreased cerebral microvascular responsiveness to CO2 (CO2 vasoreactivity). The relation between CO2 vasoreactivity and executive function is not known. Protocols to assess CO2 vasoreactivity are cumbersome and require inhaling a CO2-enriched gas. We explored the ability to measure CO2 vasoreactivity using end-tidal CO2 fluctuations during normal breathing and the association of this measure with cognitive function in hypertension.

Methods: 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% CO2 gas and hyperventilation for 2 min each. We calculated CO2 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 CO2 and blood pressure upon BFV during normal room-air respiration. Multiple regression analyses were used to correlate cerebral hemodynamics with cognitive measures.

Results: Data were collected from 41 individuals with hypertension (mean age 71 years, 24% African Americans, 61% women, off antihypertensive therapy). Lower CO2 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 CO2 vasoreactivity (R(2) = 14%, p = 0.02).

Conclusion: This study suggests that the decrease in CO2 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 CO2 vasoreactivity is possible during normal breathing. If replicated in future studies, this may offer a more convenient clinical way to assess CO2 vasoreactivity in hypertension and cognitive disorders.