Enrichment and stratification for predementia Alzheimer disease clinical trials.

The difference in annual rate of decline for CDR-SB between the Aβ + Ptau + HCs and the controls approached significance: 0.25, CI = [0.04 to 0.45], vs. 0.04, CI = [0.01 to 0.07], p = 0.061.

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In Aβ – Ptau – individuals, atrophy rates are relatively small and fairly uniform across ROIs; in contrast, Aβ + Ptau – individuals show elevated atrophy rate for the hippocampus, with the difference between Aβ – Ptau – and Aβ + Ptau – individuals approaching significance (p = 0.075).

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Although all ROIs show a clear trend for higher atrophy rates in Aβ + Ptau + group as compared with controls, differences were small and significant only for the amygdala and parahippocampal gyrus, with the isthmus cingulate approaching significance (numerical values, with 95% CIs and p-values for the comparison between groups for each ROI, are shown in File S1 , Tables S2B).

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Interestingly, the hippocampus showed a trend for elevated atrophy rate earlier in the disease process, when evidence of Aβ pathology was present, but in the absence of ptau pathology.

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