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While the propor-tion of cognitively normal subjects with the AD signaturewas unexpectedly high, the APOE e4 allele frequency wasmarkedly increased in this subgroup of normal subjectswith the AD signature (De Meyer et al., 2010), suggest-ing that the signature was able to detect preclinical AD.A meta-analysis of the diagnostic and predictive utility ofCSF phosphorylated tau levels showed it was satisfactoryfor diagnosing MCI and predicting progression of MCIto dementia but was less capable of differentiating ADfrom other types of dementia (Mitchell, 2009). The treatment depends on theetiology (if it can be identifi ed). Campbelland Stanley also point out that this design may suffer from the “error of misplaced preci-sion” because careful data collection represents a wasted effort without the opportunity forcomparison of the posttest scores with control-group or pretest scores.

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