Skip to main content

Research Repository

Advanced Search

Neuropathological profile of mild cognitive impairment from a population perspective

Stephan, Blossom C.M.; Matthews, Fiona E.; Hunter, Sally; Savva, George M.; Bond, John; McKeith, Ian G.; Ince, Paul; Brayne, Carol


Blossom C.M. Stephan

Sally Hunter

George M. Savva

John Bond

Ian G. McKeith

Paul Ince

Carol Brayne


Whether the neuropathological profile of mild cognitive impairment (MCI) reflects an intermediate state between normal aging and dementia is not clear. Identifying which phenomena initiate disease and which occur secondary to the neuropathological process is important for targeted disease prevention. Current definitions of MCI include amnestic (aMCI), nonamnestic (nMCI), and multidomain (mMCI) subtypes. In an unbiased population-based cohort of brain donors, we have determined how many individuals fulfill these criteria in the period leading up to death [n=10 (5 multidomain MCI, 4 amnestic MCI, 1 nonamnestic MCI)]. All MCI cases were collapsed into 1 group and we tested whether their pathologic profile, including markers of Alzheimer disease (AD) and vascular disease (VD), is intermediate to individuals (matched for age, sex, and education) without cognitive impairment (n=20) or dementia (n=20). The main findings are of a significant linear trend in the odds of neuritic plaques (entorhinal/ hippocampus), atrophy (hippocampal and cortical), infarcts, and small vessel disease (SVD) with increased cognitive impairment. Neuropathologically, MCI is complex, with 10% of MCI brains classified as normal, 10% as VD, 10% as AD, and 40% as mixed AD/VD, with the remaining showing other pathologies. Rather than pure pathologic changes, several different factors seem to contribute to the impairment of MCI. In MCI, both AD and non-AD pathology should be considered as possible intervention targets. Copyright © 2012 by Lippincott Williams & Wilkins.


Stephan, B. C., Matthews, F. E., Hunter, S., Savva, G. M., Bond, J., McKeith, I. G., …Brayne, C. (2012). Neuropathological profile of mild cognitive impairment from a population perspective. Alzheimer Disease and Associated Disorders, 26(3), 205-212.

Journal Article Type Review
Publication Date Jul 1, 2012
Deposit Date Dec 8, 2023
Journal Alzheimer Disease and Associated Disorders
Print ISSN 0893-0341
Publisher Lippincott, Williams & Wilkins
Volume 26
Issue 3
Pages 205-212
Public URL