title: Outcomes after diagnosis of mild cognitive impairment in a large autopsy series.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Epidemiology, University of Kentucky, Lexington, KY.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Abner
authors.affiliation: Department of Biostatistics, University of Kentucky, Lexington, KY.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kryscio
authors.affiliation: Department of Neurology, University of Kentucky, Lexington, KY.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Schmitt
authors.affiliation: Department of Biostatistics, University of Kentucky, Lexington, KY.
authors.forename: David W
authors.initials: DW
authors.lastname: Fardo
authors.affiliation: Department of Pharmacy Practice and Science, University of Kentucky, Lexington, KY.
authors.forename: Daniela C
authors.initials: DC
authors.lastname: Moga
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY.
authors.forename: Eseosa T
authors.initials: ET
authors.lastname: Ighodaro
authors.affiliation: Department of Neurology, University of Kentucky, Lexington, KY.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Jicha
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Neurology, Oregon Health & Science University, Portland, OR.
authors.forename: Hiroko H
authors.initials: HH
authors.lastname: Dodge
authors.affiliation: Division of Biostatistics, Washington University, St Louis, MO.
authors.forename: Chengjie
authors.initials: C
authors.lastname: Xiong
authors.affiliation: Department of Pathology, Oregon Health & Science University, Portland, OR.
authors.forename: Randall L
authors.initials: RL
authors.lastname: Woltjer
authors.affiliation: Department of Pathology, Rush University Medical Center, Chicago, IL.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Schneider
authors.affiliation: Department of Neurology, Washington University, St Louis, MO.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL.
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
authors.affiliation: Department of Pathology, University of Kentucky, Lexington, KY.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Nelson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology; D050379:Arteriolosclerosis / Q000145:classification / Q000473:pathology*; D001344:Autopsy; D060825:Cognitive Dysfunction / Q000145:classification / Q000473:pathology*; D003704:Dementia / Q000145:classification / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D002537:Intracranial Arteriosclerosis / Q000145:classification / Q000473:pathology*; D008297:Male; D024801:Tauopathies / Q000145:classification / Q000473:pathology*