Methods of detecting the signature of Alzheimer's disease before the clinical onset of the disease are disclosed, such as methods of diagnosing Mild Cognitive Impairment (MCI), monitoring the progress of MCI, and predicting the time to clinical onset of AD dementia. The methods use a Biomarker Severity Score, which corresponds to output signals of one or more biomarkers chosen from AD Index, Morphometric Imaging, and PKC Epsilon Biomarkers. Also disclosed are methods of screening for a compound useful for treating MCI or for preventing the clinical onset of AD dementia, as well as methods of evaluating or monitoring the therapeutic benefit of an agent for treating MCI or preventing the clinical onset of AD dementia.
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