Brain Blood Vessel Responses to Changes in Blood Flow

Global cerebral blood flow (CBF) decreases with advancing age; however, some adults have accelerated declines in CBF, placing them at a greater risk of cognitive impairment. However, there is a lack of human studies that investigate the cause or consequence of altered blood flow regulation in the brain. This study will systematically address this gap in knowledge by examining cerebrovascular control in adults during acute physiological challenges (simulated postural change test and breathing increased carbon dioxide) that stimulate a change in CBF.

• MRI (Device): Participants will undergo an MRI scan while performing breathing and a simulated postural change task.
• Prazosin (Drug): A dose of prazosin will be administered based on body weight.
• Placebo (Drug): Oral placebo

Primary outcomes

• Change in blood flow [Two study visits, up to 240 minutes]: The change in intracranial blood flow during breathing and simulated postural change tasks will be measured with MRI
• Change in blood velocity [Two study visits, up to 240 minutes]: The change in blood velocity during breathing and simulated postural change tasks will be measured with MRI.

Sex: All, ages: 55 Years to 69 Years, accepts healthy volunteers

Inclusion Criteria:

* Between the ages of 55-69 years
* Have a BMI less than or equal to 34.5 kg/m2
* Nonsmoker
* are less than 72 in (182.88 cm) height
* Females must be postmenopausal

Exclusion Criteria:

* Diagnosis of Mild Cognitive Impairment (MCI) or Alzheimer's disease (AD)
* History or evidence of hepatic disease, hematological disease, or peripheral vascular disease; severe kidney injury requiring hemodialysis
* History of cardiovascular disease including: severe congestive heart failure, coronary artery disease, ischemic heart disease (stents, coronary artery bypass grafts) and tachycardia
* Uncontrolled hypertension
* History of clinically significant ischemic or hemorrhagic stroke, or significant cerebrovascular disease
* Severe untreated obstructive sleep apnea
* History of diabetes with HbA1c greater than 9.5%
* Major neurologic disorders other than dementia (e.g., MS, ALS, brain surgery, etc.)
* Current or recent (\<1 year) major psychiatric condition (Axis I) or addictive disorders
* Significant surgical history
* Other significant medical conditions at investigators' discretion
* Contraindications to MRI
* Prescribed medications that interfere with prazosin
* Lactose allergy
* lower body will not fit in lower body negative pressure (LBNP) chamber (regardless of overall height and BMI).

• Jill Barnes, PhD, Principal investigator, UW Madison

NIH grants: 1RF1NS117746-01