Blood Brain Flow and Exercise

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.

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.)