Abstract

Abstract: Mild cognitive impairment (MCI) is a syndromic label for people with informant-corroborated memory problems and evidence of memory impairment on formal testing in the absence of more pervasive deficits in cognition and functional abilities. It is often described as a “risk factor” for dementia though this is misleading; patients with the first signs of Alzheimer's disease (AD) will meet the criteria for MCI and as their illness progresses they will move to more traditional criteria for dementia (eg, DSM). Importantly though, they have not changed or “converted” from one disease to another. The problem with MCI clinically, and hence the reason why all such patients are not simply diagnosed with very mild AD is that as one moves closer to normal performance (ie, not clearly demented), the risk of patients who do not have AD (eg, so-called “worried well”; depression; alternate degenerative or non-degenerative pathology) being captured by the MCI syndrome increases. Furthermore, although the concept of MCI seems straightforward, “absence of dementia” or “intact cognition in domains other than memory” or even “objective evidence of memory impairment” varies according to the methods used to define each criterion. Nevertheless, with longitudinal follow-up to confirm that initial MCI status was due to incipient AD, this syndrome offers a important window to examine the earliest symptomatic stages of the disease. Emerging evidence from such studies have highlighted that incipient (MCI-stage) AD is underpinned by degeneration of an interconnected neural circuit including mesial temporal lobe, diencephalon and posterior cingulate regions—all of which, interestingly, have been implicated in memory processing from focal lesion studies in humans.