Brain Blood Flow: Age and Gender

Healthy Clinical Trial

Official title:

Brain Blood Flow Response to Hypercapnia in Healthy Adults: The Effect of Age and Sex

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02840851
• Other study ID #: 2016-0403
• Secondary ID: A176000EDUC/KINE
• Status: Completed
• Start date: November 2016
• Est. completion date: September 2018

Study information

• Verified date: December 2019
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Baseline cerebral blood flow through the middle cerebral artery (MCA) and cerebral vasodilator response of the MCA to inhaled carbon dioxide (CO2) will be measured in young women, young men, older women, and older men using Magnetic Resonance (MR) imaging and transcranial Doppler ultrasound (TCD). Data collection techniques will be compared.

Description:

The investigators have recently shown that cerebral blood flow responses to chemical stimuli are reduced in healthy older adults. The investigators also have preliminary data suggesting that sex differences in cerebrovascular regulation exist. The overall goal of this application is to extend on the investigators previous studies by employing advanced neuroimaging techniques to enhance the investigators understanding of neurovascular coupling in healthy aging. This study will collect clinically significant data with implications for the future risk of cognitive decline and Alzheimer's disease.

The research aims are:

1. To determine the effect of age and sex on baseline cerebral blood flow through the middle cerebral artery (MCA).

2. To determine the effect of age and sex on cerebral vasodilator responses.

3. To determine if the cerebrovascular responses measured by transcranial Doppler ultrasound (TCD) are associated with the cerebrovascular responses measured by Magnetic Resonance (MR) imaging.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: September 2018
• Est. primary completion date: September 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 64 Years

Eligibility

Inclusion Criteria:

• Between 20-34 or 50-69 years

• Body mass index <34 kg/m2

Exclusion Criteria:

• Current smoker

• History or evidence of: hepatic disease, renal disease, hematological disease, peripheral vascular disease, stroke/neurovascular disease, diabetes, hypertension

• Part of a vulnerable population (e.g. pregnant women, prisoner, individuals lacking capacity to consent, etc.)

• Older females only: subject is not post-menopausal

Related Conditions & MeSH terms

• Aging
• Healthy
• Hypercapnia

Intervention

Device:
• MRI
Participants will undergo a MRI scan while two stepwise CO2 elevations are applied to the participant by adding fractional concentration of inspired CO2 (FICO2) at 4% and 6% each time. The end tidal CO2 (PetCO2) will be elevated and maintained constant for a few minutes at each target level. Breath-by-breath changes in respiratory rate and PetCO2 will be measured.
• TCD
Participants will undergo a TCD scan while two stepwise CO2 elevations are applied to the participant by adding fractional concentration of inspired CO2 (FICO2) at 4% and 6% each time. The end tidal CO2 (PetCO2) will be elevated and maintained constant for a few minutes at each target level. Breath-by-breath changes in respiratory and PetCO2 will be measured.

Locations

Country	Name	City	State
United States	University of Wisconsin-Madison	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
University of Wisconsin, Madison

Country where clinical trial is conducted

United States, 

References & Publications (20)

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Barnes, JN, Taylor JL, Nicholson WT, and Joyner MJ. Sex differences in age-related changes in cerebral vasodilator responses. FASEB Journal. 2013.

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Ivancev V, Bakovic D, Obad A, Breskovic T, Palada I, Joyner MJ, Dujic Z. Effects of indomethacin on cerebrovascular response to hypercapnea and hypocapnea in breath-hold diving and obstructive sleep apnea. Respir Physiol Neurobiol. 2009 May 15;166(3):152-8. doi: 10.1016/j.resp.2009.03.001. Epub 2009 Mar 18. — View Citation

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Lipsitz LA, Mukai S, Hamner J, Gagnon M, Babikian V. Dynamic regulation of middle cerebral artery blood flow velocity in aging and hypertension. Stroke. 2000 Aug;31(8):1897-903. — View Citation

Lüscher TF, Diederich D, Siebenmann R, Lehmann K, Stulz P, von Segesser L, Yang ZH, Turina M, Grädel E, Weber E, et al. Difference between endothelium-dependent relaxation in arterial and in venous coronary bypass grafts. N Engl J Med. 1988 Aug 25;319(8):462-7. — View Citation

Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. N Engl J Med. 1999 Jun 10;340(23):1801-11. Review. — View Citation

Mitchell GF, van Buchem MA, Sigurdsson S, Gotal JD, Jonsdottir MK, Kjartansson Ó, Garcia M, Aspelund T, Harris TB, Gudnason V, Launer LJ. Arterial stiffness, pressure and flow pulsatility and brain structure and function: the Age, Gene/Environment Susceptibility--Reykjavik study. Brain. 2011 Nov;134(Pt 11):3398-407. doi: 10.1093/brain/awr253. — View Citation

Newell DW, Aaslid R, Lam A, Mayberg TS, Winn HR. Comparison of flow and velocity during dynamic autoregulation testing in humans. Stroke. 1994 Apr;25(4):793-7. — View Citation

Panza JA, Quyyumi AA, Brush JE Jr, Epstein SE. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med. 1990 Jul 5;323(1):22-7. — View Citation

Selim M, Jones R, Novak P, Zhao P, Novak V. The effects of body mass index on cerebral blood flow velocity. Clin Auton Res. 2008 Dec;18(6):331-8. doi: 10.1007/s10286-008-0490-z. Epub 2008 Aug 22. — View Citation

Smith EE, Greenberg SM. Beta-amyloid, blood vessels, and brain function. Stroke. 2009 Jul;40(7):2601-6. doi: 10.1161/STROKEAHA.108.536839. Epub 2009 May 14. Review. — View Citation

Xie A, Skatrud JB, Morgan B, Chenuel B, Khayat R, Reichmuth K, Lin J, Dempsey JA. Influence of cerebrovascular function on the hypercapnic ventilatory response in healthy humans. J Physiol. 2006 Nov 15;577(Pt 1):319-29. Epub 2006 Aug 24. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Middle Cerebral Artery Blood Flow Measurement	Utilize the TCD and MR imaging to measure middle cerebral artery blood flow in the brain while the participant is at rest.	75 minutes
Primary	Middle Cerebral Artery Blood Flow Reactivity to Hypercapnia	Utilize the TCD and MR imaging to measure middle cerebral artery blood flow reactivity to hypercapnic gas.	75 minutes