Blood Brain Flow and Exercise

Study Overview
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Brief Summary
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Cerebral vasodilator responses to CO2 will be measured in young healthy adults, healthy sedentary older adults, and healthy exercise trained older adults. This variable will be examined before and after administering the cyclooxygenase inhibitor indomethacin, which has been shown to blunt cerebral vasodilator responses. In addition, the investigators will examine these counter-regulatory hemodynamic mechanisms to hypoperfusion caused by indomethacin.

Detailed Description
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Normal aging reduces cerebral blood flow and cognitive function. Aging also appears to alter functional connectivity within the brain, which is associated with cognitive functioning. Observational studies suggest that regular physical activity is associated with higher cerebral blood flow and improved cognitive function. However, the mechanistic links among regular physical activity and cerebral blood flow with advancing age are unknown. In this context, it is unclear if aging or exercise training status alters the neurovascular coupling of blood flow in the brain. Thus, the overall goal of this study is to examine the age-related changes in cerebral vasodilatory capacity, an important homeostatic mechanism and marker for effective regulation of cerebral perfusion, in order to determine how it is mechanistically linked to cognition. Additionally, the investigators will explore the potential beneficial effect of physical activity on the relationships between cerebral vasodilation and cognition in humans. The research aims are: To determine if cerebral vasodilator responses are affected by age and exercise training status in healthy adults. To compare the effect of cyclooxygenase inhibition on cerebral vasodilator responses in healthy adults. To determine the neurovascular counter-regulatory response to cyclooxygenase inhibition in healthy adults.

Official Title
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Cerebral Vasodilator Responses in Sedentary and Exercise Trained Humans

Conditions
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Cerebrovascular Circulation

Intervention / Treatment
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* Other: Control
* Drug: Indomethacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Young subjects between 18-35 years old Older subjects between 55-75 years old Nonsmokers Physically active (exercise more than 3 times per week for at least 30 minutes) Sedentary (no formal exercise over 1 hour per week). Exclusion Criteria: Outside of the specified age range Present with history or evidence of hepatic, renal, or hematological disease; peripheral vascular disease; stroke/neurovascular disease; diabetes; hypertension Take medications that indicate hepatic, renal, hematological disease; cardiovascular disease, including hypertension; stroke/neurovascular disease; and diabetes Body mass index >34 kg/m2 Take physician-prescribed medications that may interact with indomethacin: 1) cardiovascular drugs (e.g. angiotensin-converting-enzyme inhibitor (ACE inhibitors), angiotensin II receptor blockers (ARB's), Diuretics); 2) drugs that would increase bleeding risk (e.g. warfarin, heparin, clopidogrel, rivaroxaban, other NSAIDs); or 3) drugs associated with increased renal toxicity (e.g. cyclosporin, tacrolimus) Vulnerable populations (i.e. pregnant women, prisoners, individuals lacking capacity to consent, etc.)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug<br>Control-Hypercapnic Trials: Three stepwise CO2 elevations will be applied to the patient by adding fractional concentration of inspired CO2 (FICO2) at 2%, 4%, and 6% each time, balanced with room air. The end tidal CO2 (PetCO2) will be elevated and maintained constant for three minutes at each target level. Breath-by-breath changes in minute ventilation (VE) and PetCO2 will be measured. Drug-Indomethacin: Healthy volunteers, indomethacin suspension will be orally administered at 1.2 mg/kg. After drug administration, the patient will rest quietly for 90 minutes. | Other: Control<br>* Transcranial Doppler Blood Pressure Heart Rate Oxygen Saturation<br>Drug: Indomethacin<br>* Transcranial Doppler Blood Pressure Heart Rate Oxygen Saturation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral Vasodilator Responses | Utilize a Transcranial Doppler to measure blood flow velocity in response to inhaled carbon dioxide. | Measurement at baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral Vasodilator Responses | Utilize a Transcranial Doppler to measure blood flow velocity in response to inhaled carbon dioxide. | Measurement beginning 60 minutes post drug and measured through 180 minutes | 
| Blood Pressure |  | Measurement at baseline and beginning 60 minutes post drug and measured through 180 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aging, Cerebral Vasodilator Function, White Matter Hyperintensity Volume, Default Mode Network Connectivity, Cognitive Function, Cardiorespiratory Fitness