The study was approved by the Australian National University Ethics Committee and all participants provided written informed consent. Sociodemographic and health

measures Total years of education, heart problems (e.g., atrial fibrillation, angina, etc.), diabetes, stroke, anxiety and depression medication, and smoking were assessed by self-report. Hypertension was assessed Inhibitors,research,lifescience,medical using objective blood pressure measures (diastolic > 90; systolic > 140 on average of two seated measures) and self-reported antihypertensive medication use. APOE*E4 genotype was determined from DNA collected by cheek swab. Handedness measure Handedness was assessed by the Edinburgh Handedness Inventory (EHI; Oldfield 1971), a 10-item questionnaire surveying which hand is used to perform discrete tasks (e.g., “Which hand do

you use to hold a spoon?” and using a five-point scale (−2 always left, −1 mostly left, 0 either, +1 mostly right, +2 always right). A global handedness score ranging from −1 (extremely left handed) Inhibitors,research,lifescience,medical to +1 (extremely right handed) was computed by averaging all responses and dividing by two. This score was then used to produce two additional measures of handedness direction (< 0 = left; > 0 = right) and handedness strength Inhibitors,research,lifescience,medical (absolute value of the handedness score ranging from 0 to 1). MRI scan acquisition All participants were imaged with a 1.5 Tesla Philips Gyroscan ACS-NT scanner (Philips Medical Systems, Best, The LY2835219 manufacturer Netherlands) for T1-weighted 3D structural MRI. The T1-weighted MRI was acquired in coronal orientation using a fast-field Inhibitors,research,lifescience,medical echo sequence (FFE) with

the following parameters: Wave 1 repetition time (TR)/echo time (TE) = 28.05/2.64 ms, flip angle = 30°, matrix Inhibitors,research,lifescience,medical size = 256 × 256, field of view (FOV) = 260 × 260 mm, slice thickness = 2.0 mm, and mid-slice to mid-slice distance = 1.0 mm, yielding overcontiguous coronal slices; Wave 2 TR = 8.93 ms, TE = 3.57 ms, flip angle of 8°, matrix size = 256 × 256, slices 160, and FOV 256 × 256 mm. Slices were contiguous with slice thickness many of 1.5 mm. Image analysis Hippocampal and amygdalar volumes were determined by manually tracing the periphery of the Region of Interest (ROI) on each slice of a T1-weighted scan in coronal orientation using Analyze 5.0 (Brain Imaging Resource, Mayo Clinic, Rochester, MI; Fig. 1) by the same experienced tracers. The outlining of the hippocampus and amygdala always proceeded from anterior to posterior and was traced according to the protocol outlined by Watson and colleagues (Watson et al. 1997) with a modification suggested by Brierly et al. (2002). Volume estimations were repeated on 10 randomly selected scans and interclass correlations between raters ranged from 0.948 to 0.989 and 0.981 to 0.993 for the right and left hippocampus, and from 0.975 to 0.989 and 0.995 to 0.