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.
|Number of pages||11|
|Journal||Annals of Neurology|
|State||Published - Apr 2017|
Bibliographical noteFunding Information:
The Statistical Modeling of Aging and Risk of Transition study is supported by National Institute on Aging (NIA) grant R01-AG038651 (R.J.K. and F.A.S., co–principal investigators). Cohort studies were supported by NIA grants P30-AG10161 and R01-AG15819 (Religious Orders Study), R01-AG17917 (Rush Memory and Aging Project), P30-AG028383 (Biologically Resilient Adults in Neurological Studies), P50-AG005681 (Wash U Memory and Aging Project), and P30-AG008017 (Oregon Brain Aging Study, Klamath Exceptional Aging Project, African American Dementia Project). Additional support came from R01 NS014189. We thank our participants and their families; and R. Guariglia, E. Washington, and J. Gibbons for their assistance in preparing the SMART data.
© 2017 American Neurological Association
ASJC Scopus subject areas
- Clinical Neurology