OBJECTIVE: To determine clinical and neuropathological outcomes following a clinical diagnosis of mild cognitive impairment (MCI).

METHODS: Data were drawn from a large autopsy series (N = 1,337) of individuals followed longitudinally from normal or MCI status to death, derived from 4 Alzheimer Disease (AD) Centers in the United States.

RESULTS: Mean follow‐up was 7.9 years. Of the 874 individuals ever diagnosed with MCI, final clinical diagnoses were varied: 39.2% died with an MCI diagnosis, 46.8% with a dementia diagnosis, and 13.9% with a diagnosis of intact cognition. The latter group had pathological features resembling those with a final clinical diagnosis of MCI. In terms of non‐AD pathologies, both primary age‐related tauopathy (p < 0.05) and brain arteriolosclerosis pathology (p < 0.001) were more severe in MCI than cognitively intact controls. Among the group that remained MCI until death, mixed AD neuropathologic changes (ADNC; ≥1 comorbid pathology) were more frequent than “pure” ADNC pathology (55% vs 22%); suspected non‐Alzheimer pathology comprised the remaining 22% of cases. A majority (74%) of subjects who died with MCI were without “high”‐level ADNC, Lewy body disease, or hippocampal sclerosis pathologies; this group was enriched in cerebrovascular pathologies. Subjects who died with dementia and were without severe neurodegenerative pathologies tended to have cerebrovascular pathology and carry the MCI diagnosis for a longer interval.

INTERPRETATION: MCI diagnosis usually was associated with comorbid neuropathologies; less than one-quarter of MCI cases showed "pure" AD at autopsy. Ann Neurol 2017;81:549-559.

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Notes/Citation Information

Published in Annals of Neurology, v. 81, issue 4.

© 2017 American Neurological Association

This is the peer reviewed version of the following article: Abner, E. L., Kryscio, R. J., Schmitt, F. A., Fardo, D. W., Moga, D. C., Ighodaro, E. T., Jicha, G. A., Yu, L., Dodge, H. H., Xiong, C., Woltjer, R. L., Schneider, J. A., Cairns, N. J., Bennett, D. A., & Nelson, P. T. (2017). Outcomes after diagnosis of mild cognitive impairment in a large autopsy series: Outcomes of MCI. Annals of Neurology, 81(4), 549–559, which has been published in final form at https://doi.org/10.1002/ana.24903. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Version.

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Funding Information

SMART is supported by NIA grant R01-AG038651 (R. Kryscio and F. Schmitt co-PIs). Cohort studies were supported by NIA grants P30-AG10161 and R01-AG15819 (ROS), R01-AG17917 (Rush MAP), P30-AG028383 (BRAiNS/UK-ADC), P50-AG005681 (Wash U MAP), P30-AG008017 (OBAS, KEAP, AADAPt). Additional support came from R01 NS014189.