Identifying biological processes which occur at the earliest stage of progressive disease and those which are secondary to the neuropathological process is important for targeted disease prevention. Whether mild cognitive impairment (MCI) has a distinct neuropathological profile which constitutes an intermediate state between no cognitive impairment and dementia is not clear. In this review, Stephan and colleagues summarize current evidence and conclude that mild cognitive impairment is neuropathologically complex and cannot be understood within a single framework. Pathological changes identified in MCI include plaque and tangle formation, vascular pathologies, neurochemical deficits, cellular injury, inflammation, oxidative stress, mitochondrial and genomic activity changes, synaptic dysfunction, disturbed protein metabolism and disrupted metabolic homeostasis. Determining which factors primarily drive neurodegeneration and dementia and which are secondary in disease progression requires further research. They suggest that standardization of the definition of MCI and reporting of pathology is needed for building an integrated picture of the clinical and neuropathological profile of MCI.

Stephan BCM, Hunter S, Harris D, Llewellyn DJ, Siervo M, Matthews FE and Brayne C: The neuropathological profile of mild cognitive impairment (MCI): a systematic review. Molecular Psychiatry 17:1056-1076 (2012) | doi:10.1038/mp.2011.147

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