Participants

The study was approved by the ethical review board of the Texas Southwestern Medical Center at Dallas, University of Texas at Dallas and The Cooper Institute. All participants provided written informed consent before participating in the study. Participants (n = 137) were recruited from a database at The Cooper Institute, through flyers/advertisements placed in local newspapers and magazines, and our institutions' websites. Participants were included if their self-reported physical activity was described as participating in aerobic physical activity less than or equal to twice a week for 20 min for at least the preceding 3 months. This history was ascertained in the initial phone screen by The Cooper Institute and confirmed during the phone screen by the Center for BrainHealth, given the unreliable nature of self-reported physical activity. All levels of physical activity below this cut-point were considered for enrollment including those who were physically inactive.

All participants underwent the Telephone Interview of Cognitive Status-Modified (TICS-M) to screen for dementia (de Jager et al., 2003), the Montreal Cognitive Assessment (MoCA) to screen for cognitive impairment (Nasreddine et al., 2005), the Beck Depression Inventory 2nd edition (BDI-II) to screen for depressive symptoms (Beck and Brown, 1996), and complete medical, physical, and laboratory assessments by a physician to ensure good general health. The criteria for inclusion were no history of neurological or psychiatric conditions, normal IQ range, native English speakers, and minimum of high school diploma. Exclusionary criteria included: MR scanning contraindications, cognitive status (TICS-M < 28 and MoCA < 26), depression indication (BDI > 14), left-handedness, body mass (BMI > 40, mass(kg)height(m)2). The participant's BMI was limited to 40 to ensure participants' bodies and heads fit in the scanner and the head coil.

After passing the initial phone screens, individuals were further evaluated at The Cooper Institute for any medical history including medications and physical activity history and a physical examination including blood pressure, height/weight, BMI, and waist circumference. At this point, the participants underwent graded exercise stress testing to evaluate for obstructive coronary artery disease or other findings that would represent contraindications to exercise and for measurement of the cardiorespiratory fitness level (VO₂ Max). VO₂ Max is a measure of maximum capacity of the body to use and transport oxygen. Participants were tested utilizing a Lode—Excalibur Sport cycle ergometer, (Groningen, Netherlands) and a Jaeger Oxycon Pro, (Hoechberg, Germany), to assess VO₂ Max and exercise electrocardiogram. Maximum effort was strongly encouraged during the testing and all included participants had reached at least 85% of their maximum predicted heart rate to ensure that evaluation for ischemic findings was clinically acceptable. Blood pressure and ECG responses to exercise were monitored and ratings of perceived exertion (RPE) were obtained using the Borg scale: 6 (no exertion) to 20 (extremely difficult). Further exclusion criteria included abnormal electrocardiographic response, significant hypertensive blood pressure response to exercise, inability to reach 85% of maximum predicted heart rate for age or not completing maximal exercise effort/test.

Participants who met the above inclusion criteria (n = 67) were randomized using a block randomization schedule stratified by gender (ClinicalTrials.gov, NCT# 00977418) into one of three groups: cognitive training (n = 25), physical training (n = 21), or wait-listed control (n = 21) group. However, seven participants in cognitive training, three participants in physical training and two participants in control groups declined to participate in the study. Thus, the final participant numbers were: cognitive training (CT, n = 18), physical training (PT, n = 18), and control (CN, n = 19), see Figure S1. The present study included 36 cognitively normal adults (mean age = 63.5 ± 3.8; 56–75 years of age) who completed the cognitive or physical training programs. Participants were not compensated for their involvement in this study. Written informed consent was obtained from all subjects in accordance with the Institutional Review Board (IRB) of our academic institutions: The University of Texas at Dallas, The University of Texas Southwestern Medical Center and The Cooper Institute.