Material and Methods Participants The sample consisted of 52 participants with complete neuropsychological, medical, and demographic data (see Table ​Table1).1). This sample size was reduced from 95 due to missing data, however, those excluded were not significantly different in terms of age (t(92) = −0.99, P = 0.32), gender (χ2 (1, N = 95) = 0.55, P = 0.46),

education (t(83) = −1.70, P = 0.09), global cognitive status (t(64.97) = −0.99, P = 0.33), cardiac function (t(87) = −1.12, Inhibitors,research,lifescience,medical P = 0.27), or in terms of comorbid medical conditions such as diabetes (χ2 (1, N = 95) = 0.85, P = 0.36), though there was a trend for hypertension (χ2 (1, N = 95) = 3.83, P = 0.05). Participants were recruited from either outpatient cardiology offices or from advertisements in local papers. The inclusion criteria were

English-speaking and normal or corrected vision at the time of testing. Potential participants were excluded Inhibitors,research,lifescience,medical for significant neurological disease (e.g., history of stroke, multiple sclerosis), moderate or severe traumatic brain injury (with loss of consciousness), diagnosis of a current psychiatric illness, history of substance abuse with subsequent hospitalization, or any contraindications for magnetic resonance imaging (MRI; e.g., some metal implants). Participants were administered a comprehensive neuropsychological battery. Institutional Inhibitors,research,lifescience,medical Review Board approval

was granted and written Inhibitors,research,lifescience,medical informed consent was obtained from all participants prior to testing. Table 1 Demographic and medical characteristics (N = 52) Procedures Arterial spin labeling All scans were performed using a 3 T Siemens Tim Trio scanner (Siemens, Erlangen, Germany) located on the Brown University campus. A 32 channel head receive array was used with body resonator transmit coil, and participants were placed head first in the supine position. Foam pads were placed in the space around the head to limit motion, and participants were provided with Inhibitors,research,lifescience,medical hearing protection in the form of foam earplugs and headphones. Following acquisition of a three-axis localizer scan, a 3D T1-MPRAGE scan was acquired with 1 mm isotropic resolution. Drug_discovery This scan was acquired using parameters TR = 1900 msec, TE = 2.98 msec, TI = 900 msec, and readout flip angle = 9 to provide a 3D T1 image dataset for gray–white matter segmentation and morphometric analyses. ASL scans were acquired using PICORE-Q2TIPS (Wong et al. 1998; Luh et al. 1999), a Siemens product sequence that is distributed with their MRI scanners. This widely used pulsed ASL sequence has demonstrated reliability and validity (Jahng et al. 2005; Liu and Brown 2007; Noguchi et al. 2007; Petersen et al. 2010). In brief, differences between 71 pairs of tagged and control ASL volumes were averaged to create individual mean perfusion maps.