To examine feasibility and test-retest reliability of encoding-task functional MRI (fMRI) in mild Alzheimer’s disease (AD).
Randomized, double-blind, placebo-controlled (RCT) study.
Memory clinical trials unit.
Twelve subjects with mild AD (MMSE 24.0±0.7, CDR 1), on >6 months stable donepezil, from the placebo-arm of a larger 24-week (n=24, four scans on weeks 0,6,12,24) study.
Placebo and three face-name paired-associate encoding, block-design BOLD-fMRI scans in 12 weeks.
Whole-brain t-maps (p<0.001, 5-contiguous voxels) and hippocampal regions-of-interest (ROI) analyses of extent (EXT, %voxels active) and magnitude (MAG, %signal change) for Novel-greater-than-Repeated (N>R) face-name contrasts. Calculation of Intraclass Correlations (ICC) and power estimates for hippocampal ROIs.
Task-tolerability and data yield were high (95 of 96 scans yield good quality data). Whole-brain maps were stable. Right and left hippocampal ROI ICCs were 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.
Encoding-task fMRI was successfully implemented in a single-site, 24-week, 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 these results with larger sample sizes and assessment in multi-site studies is warranted.