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.
Digital Object Identifier (DOI)
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.
Abner, Erin L.; Kryscio, Richard J.; Schmitt, Frederick A.; Fardo, David W.; Moga, Daniela C.; Ighodaro, Eseosa T.; Jicha, Gregory A.; Yu, Lei; Dodge, Hiroko H.; Xiong, Chengjie; Woltjer, Randall L.; Schneider, Julie A.; Cairns, Nigel J.; Bennett, David A.; and Nelson, Peter T., "Outcomes after Diagnosis of Mild Cognitive Impairment in a Large Autopsy Series" (2017). Epidemiology Faculty Publications. 70.