Objective To examine feasibility and test-retest reliability of encoding-task useful MRI (fMRI) in gentle Alzheimer’s disease (Advertisement). and power estimations for hippocampal ROIs. Outcomes Task-tolerability and data produce had been TH-302 high (95 of 96 scans produce top quality data). Whole-brain maps had been stable. Best and remaining hippocampal ROI ICCs had been 0.59-0.87 and 0.67-0.74 respectively. To detect 25-50% changes in 0-12 week hippocampal activity using L/R-EXT or R-MAG with 80% power (2-sided-α=0.05) requires 14-51 subjects. Using L-MAG requires >125 subjects due to relatively small signals to variance ratios. Conclusions Encoding-task fMRI was successfully implemented in a single-site 24 AD RCT. Week 0-12 whole-brain t-maps were stable and test-retest reliability of hippocampal fMRI measures ranged from moderate to substantial. Right hippocampal-MAG may be the most promising of these candidate measures in a leveraged context. These initial estimates of test-retest reliability and power justify evaluation of encoding-task fMRI as a potential biomarker for “signal-of-effect” in exploratory and proof-of-concept trials in mild AD. Validation of the total outcomes with much larger test sizes and evaluation in multi-site research is warranted. anatomically-defined hippocampal ROIs28. For assessment secondary analyses had been performed on non-hippocampal anatomically-defined ROIs including bilateral precuneus and posterior cingulate cortices acquired in template space using the MarsBaR software (http://marsbar.sourceforge.net/) which have previously shown robust and selective task-related and spatio-temporally correlated activity with this fMRI paradigm1. Repeated-measures ANCOVAs evaluated changes in medical actions in the 12-weeks between T1-T3 fMRIs. Test-retest Dependability of fMRI Activations in dependability ROIs Test-retest dependability for EXT and MAG of N>R activity from baseline(T1) to week-12(T3) fMRIs had been evaluated using two complementary techniques: intraclass relationship coefficients (ICC) utilizing a variant of ICC evaluating agreement of rating values (not only relationship) for arbitrary effects models described by Shrout and Fleiss (1979) as “ICC(2 1 for dependability at an individual time and “ICC(2 k)” for your of the average rating TH-302 across k period factors29 (discover eMethods on-line) and power evaluation/test size dedication30. Since there is absolutely no standard or broadly accepted description for general adjectives that explain reliability actions/ICC ideals/runs we thought we would adopt traditional terminology by using the definition proposed by Shrout (1998)31 when qualitatively referring to ICCs values/ranges as follows: chosen thresholds of p=0.001 and 5-voxel extent. Figure 2 Mean +/? SEM MAG (percent signal change PSC) and EXT (percentage voxels active PVA) of N>R contrast BOLD fMRI signal in the left and right Hippocampal ROIs across the three T1 (baseline week 0) T2 (week 6) and T3 (week TH-302 12) scans. TH-302 … Intraclass Correlations Power and Sample Size Analysis Table 3 displays TH-302 hippocampal ICCs with and without adjustment for potential “Baseline CDR-sb by time” interactions which were found to be significant in repeated measures ANCOVA for the right hippocampus and estimated sample sizes required to detect 25% 50 and 75% mean changes from baseline on EXT and MAG fMRI Gata3 measures based on 80% power with a 2-sided-α=0.05. To provide greatest generalizability individual-ICCs (i.e. single-ICCs) were calculated using a random subjects term. Mean-ICCs (averaged across three scans) are also reported (see eMethods). Table 3 Intraclass Correlation Coefficients (ICCs) and Predicted Sample Size Estimates for Left and Right Hippocampal ROIs. For the right hippocampus higher baseline CDR-sb scores were associated with larger rates of decline in hippocampal activity (p<0.01 corrected for multiple comparisons). Adjusted ICCs which pre-removed variance due to CDR-sb by time interactions increased ICC estimates for right hippocampus only. For RH-EXT a raw individual-ICC of 0.33 yielded an adjusted individual-ICC of 0.59 while a raw mean-ICC of 0.5 yielded an adjusted mean-ICC of 0.75. For the RH-MAG a raw individual-ICC of 0.67 yielded an adjusted individual-ICC of 0.87 TH-302 while a raw mean-ICC of 0.8 yielded an adjusted mean-ICC.