Aerobic Exercise and Cerebrovascular Function

To address the growing healthcare challenges of an aging Veteran population it is critical to understand effective rehabilitation techniques that mitigate age-related co-morbidity and improve quality of life. To date, exercise is one of a few proven interventions that attenuates age-related declines in brain health and function. A consistent but unexplained finding in many of these studies is a change in the cortical activation pattern during task, assessed using blood-oxygen-level dependent (BOLD) signal with fMRI that corresponds with improved task performance. Two key metrics of cerebrovascular health and functioning that are unexplored but may influence the documented changes in the BOLD response that is observed with post-aerobic activity are: 1) changes in resting or basal cerebral blood flow (perfusion) to key brain regions; and 2) changes in the ability of cerebrovasculature to dilate in the face of increased demand, termed cerebrovascular reactivity (CVR). The investigators' goal is to quantify the impact of aerobic exercise on cerebrovascular function and how both perfusion and CVR contributes to the BOLD signal during task-based fMRI. Consistent with the investigators' previous aging and exercise studies participants will complete one of two conditions; 1) an aerobic, interval-training intervention (Spin; n= 44), or 2) a non-aerobic, stretching control condition (Control; n=44). Cardiovascular fitness, arterial spin labeling for basal cerebral perfusion, CVR, task-based fMRI (cognitive-executive and motor), and behavioral outcomes will be assessed before and after the interventions. The specific aims will determine the effect of a 12-week aerobic exercise intervention on changes in cerebral perfusion and CVR in older Veterans. The investigators hypothesize that compared to the Control group, the aerobically-trained group will have increased basal perfusion and CVR in areas that demonstrate age-related decline and that have been demonstrated to be malleable to aerobic exercise (inferior frontal and motor cortices).

Research over the last few decades have driven the continual promotion of exercise as one of the most impactful interventions of central nervous system health and function. At the forefront of much of this research is the use of task-based fMRI BOLD to quantify beneficial changes in cortical function following aerobic exercise. While transformative, the true impact of this research is limited in scope until the investigators can define the influence of cerebrovascular function on the well-documented beneficial change in BOLD response. The investigators do know that older adults who are physically active have improved vascular health but do not know the full impact of an exercise intervention on cerebrovascular health. If the hypotheses of improved perfusion and CVR is supported it would inform current intervention strategies and would add important additional information about the potential of exercise to improve brain health in aging. This would have implications for aging Veterans at risk for neurodegenerative disease brought on by cerebrovascular dysfunction.

Inclusion criteria

• Adults aged 65-80 who do not regularly exercise

• defined as exercising less than 20 minutes twice per week
• Are willing and able to cooperate with assessments and interventions
• Participant will be quantified at or below the "poor" range for cardiovascular fitness as assessed by a volume of oxygen (VO2) test

• 26.0 ml/kg/min for males
• 21.0 ml/kg/min for females)
• 26 on the MoCA to meet the criteria for cognitively intact
• Participants will be free from diseases affecting cognition or that would interfere with their ability to engage in aerobic exercise - including but not limited to:

• chronic heart
• liver
• kidney disease
• Free from diseases/injuries directly affecting brain functions - including but not limited to:

• significant closed head injury
• open intracranial wounds
• stroke
• epilepsy
• degenerative diseases of the nervous system
• All subjects will speak English as a primary language and will have at minimum a high school diploma so that behavioral/cognitive measures reflect effects of aging and aerobic exercise and not unfamiliarity with the English language or a lack of education

Exclusion criteria

• Potential participants with major psychiatric disorder - including but not limited to:

• psychosis
• major depression
• bipolar disorder
• Individuals with ongoing drug or alcohol abuse and severe hypertension (systolic BP > 200 or diastolic BP > 110 mm Hg or subjects taking three or more antihypertensive medications
• Participants must not have conditions incompatible with MRI - including but not limited to:

• ferrous metal implants
• cardiac pacemakers or similar devices
• claustrophobia
• morbid obesity
• Persons engaging in significant skilled manual movements regularly will be excluded so that behavioral/motor measures reflect the effects of age and aerobic exercise and not the effects of frequent practice