The procedure for co-registration of the MRI and PiB PET images has been described.18 (link) Regions-of-interest (ROIs) were hand-drawn on a template that was a high-resolution MR image of a single elderly MCI subject.19 (link) The ROIs included five primary cortical areas [i.e., anterior cingulate (ACG), frontal cortex (FRC), lateral temporal cortex (LTC), parietal cortex (PAR), precuneus cortex (PRC) which comprised the Global-5 composite region], as well as medial temporal cortex (MTC), anterior ventral striatum (AVS), occipital cortex (OCC), occipital pole (OCP), sensorimotor cortex (SMC), thalamus (THL), subcortical white matter (SWM), pons (PON), and cerebellum (CER)]. PiB retention was measured using the standardized uptake value ratio (SUVR) over the 50-70 min scan (or SUV: scaled to injected dose and body mass) that is then normalized by the SUV of the CER reference region.
All statistical analyses were performed using SAS (version 9.2; SAS Institute Inc., Cary, NC, USA). All two-sample comparisons were evaluated using a Wilcoxon nonparametric test. In settings where the sample size was below 25 in any group, exact methods were used for the computation of the significance level. For the analysis of the neuropsychological outcomes, the significance levels for the two sample comparisons were computed from a linear regression model including age, gender, and education. Each model was evaluated using regression diagnostics to identify potentially influential observations. When a Cook's D value greater than 0.2 was observed, the corresponding model was recomputed with the observation removed from the data set. These instances are denoted in the tables and text.
A two-way ANOVA model was performed with diagnosis (NC and MCI) and PiB status (PiB-negative and PiB-positive) as grouping factors to determine voxel-wise gray matter differences. The interaction effect between diagnosis and PiB status, and the main effects were examined using appropriate contrasts. Analysis of covariance was also performed in SPM8 to determine voxel-wise gray matter differences between groups: PIB-negative NC > PIB-positive MCI and PIB-negative NC > PIB-negative MCI. These models included age and gender as covariates and were applied to gray matter maps with intensity threshold masking of 0.3. Thresholds of 0, 0.2 and 0.3 were examined but the latter was chosen because this provided a good compromise between inclusion of gray matter and exclusion of background instabilities. Significance levels were set to p<0.025, FDR corrected.
All statistical analyses were performed using SAS (version 9.2; SAS Institute Inc., Cary, NC, USA). All two-sample comparisons were evaluated using a Wilcoxon nonparametric test. In settings where the sample size was below 25 in any group, exact methods were used for the computation of the significance level. For the analysis of the neuropsychological outcomes, the significance levels for the two sample comparisons were computed from a linear regression model including age, gender, and education. Each model was evaluated using regression diagnostics to identify potentially influential observations. When a Cook's D value greater than 0.2 was observed, the corresponding model was recomputed with the observation removed from the data set. These instances are denoted in the tables and text.
A two-way ANOVA model was performed with diagnosis (NC and MCI) and PiB status (PiB-negative and PiB-positive) as grouping factors to determine voxel-wise gray matter differences. The interaction effect between diagnosis and PiB status, and the main effects were examined using appropriate contrasts. Analysis of covariance was also performed in SPM8 to determine voxel-wise gray matter differences between groups: PIB-negative NC > PIB-positive MCI and PIB-negative NC > PIB-negative MCI. These models included age and gender as covariates and were applied to gray matter maps with intensity threshold masking of 0.3. Thresholds of 0, 0.2 and 0.3 were examined but the latter was chosen because this provided a good compromise between inclusion of gray matter and exclusion of background instabilities. Significance levels were set to p<0.025, FDR corrected.
