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It has long been recognized that Alzheimer disease (AD), by nature a slowly progressive degenerative illness, must pass through a prodromal period during which symptoms are mild or barely detectable despite active disease. Prompted by insights into the molecular pathogenesis of AD that offer hope for treatment, techniques like neuropsychology and brain imaging have been refined to detect evidence of AD in mildly affected individuals in order to identify those who might benefit most from early intervention. This approach has culminated in the identification and definition of the syndrome of mild cognitive impairment (MCI).1,2 MCI has further been divided into amnestic syndromes (aMCI), generally believed to represent prodromal AD, and syndromes characterized by aphasic, dysexecutive, or other neurobehavioral profiles that might reflect early evidence of other disorders such as frontotemporal lobar degeneration or vascular dementia.3
A fundamental question in research on MCI is whether and how those who develop dementia are different from those who do not. Many studies follow subjects with aMCI in order to define factors that …
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