Cerebrovascular Circulation
Conditions
Keywords
Cerebral Vasodilator Function, White Matter Hyperintensity Volume, Default Mode Network Connectivity, Cognitive Function, Cardiorespiratory Fitness, Aging
Brief summary
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
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: 1. To determine if cerebral vasodilator responses are affected by age and exercise training status in healthy adults. 2. To compare the effect of cyclooxygenase inhibition on cerebral vasodilator responses in healthy adults. 3. To determine the neurovascular counter-regulatory response to cyclooxygenase inhibition in healthy adults.
Interventions
OTHERControl
1. Transcranial Doppler 2. Blood Pressure 3. Heart Rate 4. Oxygen Saturation
DRUGIndomethacin
1. Transcranial Doppler 2. Blood Pressure 3. Heart Rate 4. Oxygen Saturation
Sponsors
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cerebral Vasodilator Responses | Measurement at baseline | Utilize a Transcranial Doppler to measure blood flow velocity in response to inhaled carbon dioxide. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cerebral Vasodilator Responses | Measurement beginning 60 minutes post drug and measured through 180 minutes | Utilize a Transcranial Doppler to measure blood flow velocity in response to inhaled carbon dioxide. |
| Blood Pressure | Measurement at baseline and beginning 60 minutes post drug and measured through 180 minutes | — |
Countries
United States
Outcome results
None listed