Clinical Prediction of Alzheimer Disease Dementia Across the Spectrum of Mild Cognitive Impairment

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Abstract
As putative disease-modifying therapies for Alzheimer disease (AD) enter clinical trials, interest is growing in identifying the disease at an early “prodromal” clinical phase prior to dementia, with the hope that therapeutic intervention can slow the progression of neuropathological features and symptoms.1-3 This transitional continuum, when patients are no longer clinically normal but do not yet have dementia, is most commonly referred to as mild cognitive impairment (MCI).4 At the more impaired end of this spectrum, when individuals are more likely to present for neurological or psychiatric evaluation and meet diagnostic criteria for MCI as implemented in clinical trials, substantial AD neuropathological features and neuronal loss may already be present.5-9 It would be ideal to intervene with disease-modifying therapies even earlier, when individuals are at the less impaired end of this spectrum and presumably have a lesser degree of pathological features.