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

Ann Neurol. 2017 Apr;81(4):549-559. doi: 10.1002/ana.24903. Epub 2017 Mar 22.

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.

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.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / pathology
  • Arteriolosclerosis / classification
  • Arteriolosclerosis / pathology*
  • Autopsy
  • Cognitive Dysfunction / classification
  • Cognitive Dysfunction / pathology*
  • Dementia / classification
  • Dementia / pathology*
  • Female
  • Follow-Up Studies
  • Humans
  • Intracranial Arteriosclerosis / classification
  • Intracranial Arteriosclerosis / pathology*
  • Male
  • Tauopathies / classification
  • Tauopathies / pathology*