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The neuropathological profile of mild cognitive impairment (MCI): a systematic review

Lookup NU author(s): Professor Bloss Stephan, Dr Mario Siervo, Professor Fiona MatthewsORCiD, Professor Carol Brayne


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Whether mild cognitive impairment (MCI) has a distinct neuropathological profile that reflects an intermediate state between no cognitive impairment and dementia is not clear. Identifying which biological events occur at the earliest stage of progressive disease and which are secondary to the neuropathological process is important for understating pathological pathways and for targeted disease prevention. Many studies have now reported on the neurobiology of this intermediate stage. In this systematic review, we synthesize current evidence on the neuropathological profile of MCI. A total of 162 studies were identified with varied definition of MCI, settings ranging from population to specialist clinics and a wide range of objectives. From these studies, it is clear that MCI is neuropathologically complex and cannot be understood within a single framework. Pathological changes identified include plaque and tangle formation, vascular pathologies, neurochemical deficits, cellular injury, inflammation, oxidative stress, mitochondrial changes, changes in genomic activity, synaptic dysfunction, disturbed protein metabolism and disrupted metabolic homeostasis. Determining which factors primarily drive neurodegeneration and dementia and which are secondary features of disease progression still requires further research. Standardization of the definition of MCI and reporting of pathology would greatly assist in building an integrated picture of the clinical and neuropathological profile of MCI.

Publication metadata

Author(s): Stephan BC, Hunter S, Harris D, Llewellyn DJ, Siervo M, Matthews FE, Brayne C

Publication type: Article

Publication status: Published

Journal: Molecular Psychiatry

Year: 2012

Volume: 17

Issue: 11

Pages: 1056-1076

Print publication date: 01/11/2012

Online publication date: 06/12/2011


DOI: 10.1038/mp.2011.147

PubMed id: 22143004


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