title: Mild cognitive impairment: pathology and mechanisms.
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.
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, 1735 West Harrison St., Suite 300, Chicago, IL 60612, USA. emufson@rush.edu
authors.forename: Elliott J
authors.initials: EJ
authors.lastname: Mufson
authors.forename: Lester
authors.initials: L
authors.lastname: Binder
authors.forename: Scott E
authors.initials: SE
authors.lastname: Counts
authors.forename: Steven T
authors.initials: ST
authors.lastname: DeKosky
authors.forename: Leyla
authors.initials: L
authors.lastname: de Toledo-Morrell
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Ginsberg
authors.forename: Milos D
authors.initials: MD
authors.lastname: Ikonomovic
authors.forename: Sylvia E
authors.initials: SE
authors.lastname: Perez
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scheff
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000209:etiology / Q000473:pathology*; D018450:Disease Progression; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009414:Nerve Growth Factors / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology; D011950:Receptors, Cholinergic / Q000378:metabolism; D013569:Synapses / Q000648:ultrastructure
chemical_list: D009414:Nerve Growth Factors; D011950:Receptors, Cholinergic
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