While it is well established that physical inactivity is a modifiable risk factor for vascular disease and cognitive decline, the mechanism by which exercise exerts its protective effect on the cerebral circulation and cognition is unknown. This knowledge gap was recognized recently in the Centers for Disease Control & Prevention and the Alzheimer's Association document "National Public Health Road Map to Maintaining Cognitive Health". Our rationale for these studies is that the identification of physical exercise as a lifestyle factor able to improve cerebrovascular reserve and cognition would establish a strong scientific framework justifying design of a randomized clinical trial that could evaluate the role of physical activity in cerebrovascular health and function.

This research is based on data we obtained from a cross-sectional study that showed significant relations between physical fitness, vascular regulation and cognition. Cerebrovascular reserve and cognition were better maintained in women who were physically active but reduced in women who were sedentary. Our central hypothesis is that regular aerobic exercise mitigates age-related decreases in cerebrovascular reserve, which in turn imparts benefits in cognition. Further, we believe that these effects will persist after the structured aerobic exercise program is terminated.

Our 18 month study began with a 6-month baseline period, followed by a 6-month exercise intervention, and a 6-month follow-up period. In addition, there are 5-year and 10-year follow-up periods. Volunteers (men and women aged ≥ 55 years) from the community were recruited using a variety of recruitment methods including media and distribution lists. After the baseline (pre-training) measurements, participants underwent a six-month aerobic training program, following guidelines previously used by us and according to the new exercise guidelines for older adults established by American College of Sports Medicine and the American Heart Association. The study involves comprehensive assessments of physical fitness, cerebrovascular responses to carbon dioxide at rest and during sub-maximal exercise, and an extensive battery of cognitive function tests.

Inclusion Criteria:

• sedentary status (engages in less than 30 minutes of moderate exercise four days per week or 20 continuous minutes of vigorous exercise two days per week), the ability to walk independently outside or on stairs, body mass index (BMI) < 35 kg/m^2, women were at least 12 months postmenopausal on entry into the study

Exclusion Criteria:

• heart/chest pain upon physical exertion, fainting spells/dizziness, surgery or major trauma in the previous 6 months, known asthma or sleep apnea, history of myocardial infarction, angina, arrhythmia, valve disease, chronic heart failure, history of stroke, cardiovascular or cerebrovascular disease, history of chronic headache or migraines, history of blood clots/thrombosis, smokers (within last 12 months), currently taking medication (beta-blockers, anti-depressants, digitalis/digoxin, blood thinners (warfarin), evista (raloxifene), corticosteroids (e.g., prednisone), adrenaline/epinephrine, anti-arrhythmics (e.g., norpace)).