Outcomes after diagnosis of mild cognitive impairment in a large autopsy series

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