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

• Published in: Annals of neurology 2017-04, Vol.81 (4), p.549-559
• Main Authors: 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., Nelson, Peter T.
• Format: Article
• Language: English
• Subjects: Age; Aged; Aged, 80 and over; Alzheimer Disease - pathology; Alzheimer's disease; Arteriolosclerosis - classification; Arteriolosclerosis - pathology; Autopsies; Autopsy; Brain; Cerebrovascular system; Cognition; Cognitive ability; Cognitive Dysfunction - classification; Cognitive Dysfunction - pathology; Comorbidity; Death; Dementia; Dementia - classification; Dementia - pathology; Dementia disorders; Diagnosis; Enrichment; Fatalities; Female; Follow-Up Studies; Hippocampus; Humans; Impairment; Intracranial Arteriosclerosis - classification; Intracranial Arteriosclerosis - pathology; Lewy bodies; Lewy body disease; Male; Mortality; Neurodegenerative diseases; Pathology; Sclerosis; Series (mathematics); Tau protein; Tauopathies - classification; Tauopathies - pathology
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.24903

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