Mild cognitive impairment: Pathology and mechanisms

Document Type

Article

Abstract

Mild cognitive impairment (MCI) is rapidly becoming one of the most common clinical manifestations affecting the elderly. The pathologic and molecular substrate of people diagnosed with MCI is not well established. Since MCI is a human specific disorder and neither the clinical nor the neuropathological course appears to follow a direct linear path, it is imperative to characterize neuropathology changes in the brains of people who came to autopsy with a well-characterized clinical diagnosis of MCI. Herein, we discuss findings derived from clinical pathologic studies of autopsy cases who died with a clinical diagnosis of MCI. The heterogeneity of clinical MCI imparts significant challenges to any review of this subject. The pathologic substrate of MCI is equally complex and must take into account not only conventional plaque and tangle pathology but also a wide range of cellular, biochemical and molecular deficits, many of which relate to cognitive decline as well as compensatory responses to the progressive disease process. The multifaceted nature of the neuronal disconnection syndrome associated with MCI suggests that there is no single event which precipitates this prodromal stage of AD. In fact, it can be argued that neuronal degeneration initiated at different levels of the central nervous system drives cognitive decline as a final common pathway at this stage of the dementing disease process. © 2011 Springer-Verlag.

Keywords

Alzheimer's disease, Amyloid, Cholinergic, Dementia, MCI, Molecular, Neurofibrillary tangles, Neuropathology, Neurotrophins, Synapses

Publication Date

1-1-2012

Publication Title

Acta Neuropathologica

ISSN

00016322

E-ISSN

14320533

Volume

123

Issue

1

First Page

13

Last Page

30

PubMed ID

22101321

Digital Object Identifier (DOI)

10.1007/s00401-011-0884-1

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