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

• Type of Material: Article
• Authors: Ihab Hajjar, Emory University; Vasilis Marmerelis, University of Southern California; Dae C. Shin, University of Southern California; Helena Chui, University of Southern California
• Language: English
• Date: 2014-09-01
• Publisher: Karger Publishers
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 S. Karger AG, Basel.
• Final Published Version (URL): http://dx.doi.org/10.1159/000365349
• Title of Journal or Parent Work: Cerebrovascular Diseases
• ISSN: 1015-9770
• Volume: 38
• Issue: 1
• Start Page: 10
• End Page: 16
• Grant/Funding Information: Dr. Hajjar and the AVEC trial are supported by grant 1 K23 AG030057 from the National Institute on Aging.; This work was supported in part by the Biomedical Simulations Resource at the University of Southern California under NIH/NIBIB grant P41-EB001978.
• Keywords: Life Sciences & Biomedicine; Science & Technology; Clinical Neurology; HEMODYNAMICS; AUTOREGULATION; Trail-Making Test; Cerebral blood flow; ARTERIAL-PRESSURE; RISK; Neurosciences & Neurology; TRAIL; Hypertension; CEREBRAL-BLOOD-FLOW; HEALTHY HUMANS; Cardiovascular System & Cardiology; IMPAIRMENT; STROKE; Peripheral Vascular Disease
• Research Categories: Psychology, Cognitive; Biology, Neuroscience

Abstract

Background: Hypertension is associated with cognitive deficits, particularly executive function, and decreased cerebral microvascular responsiveness to CO<inf>2</inf> (CO<inf>2</inf> vasoreactivity). The relation between CO<inf>2</inf> vasoreactivity and executive function is not known. Protocols to assess CO<inf>2</inf> vasoreactivity are cumbersome and require inhaling a CO<inf>2</inf> -enriched gas. We explored the ability to measure CO<inf>2</inf> vasoreactivity using endtidal CO<inf>2</inf> 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% CO<inf>2</inf> gas and hyperventilation for 2 min each. We calculated CO<inf>2</inf> 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 non-linear principal dynamic modes (PDM), which modelled the dynamic effect of fluctuations in end-tidal CO<inf>2</inf> 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 CO<inf>2</inf> 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<inf>2</inf> vasoreactivity (R 2 = 14%, p = 0.02). Conclusion: This study suggests that the decrease in CO<inf>2</inf> 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<inf>2</inf> vasoreactivity is possible during normal breathing. If replicated in future studies, this may offer a more convenient clinical way to assess CO<inf>2</inf> vasoreactivity in hypertension and cognitive disorders.