  INTRODUCTION: Heterogeneity in the progression of Alzheimer's disease makes
it challenging to predict the rate of cognitive and functional decline for
individual patients. Tools for short-term prediction could help enrich clinical
trial designs and focus prevention strategies on the most at-risk patients.
METHOD: We built a prognostic model using baseline cognitive scores and
MRI-based features to determine which subjects with mild cognitive impairment
remained stable and which functionally declined (measured by a two-point
increase in CDR-SB) over 2 and 3-year follow-up periods, periods typical of the
length of clinical trials. RESULTS: Combining both sets of features yields 77%
accuracy (81% sensitivity and 75% specificity) to predict cognitive decline at
2 years (74% accuracy at 3 years with 75% sensitivity and 73% specificity).
Using this tool to select trial participants yields a 3.8-fold decrease in the
required sample size for a 2-year study (2.8-fold decrease for a 3-year study)
for a hypothesized 25% treatment effect to reduce cognitive decline.
DISCUSSION: This cohort enrichment tool could accelerate treatment development
by increasing power in clinical trials.
