Resistance to Alzheimer disease neuropathologic changes and apparent cognitive resilience in the Nun and Honolulu-Asia Aging Studies

Caitlin S. Latimer, C. Dirk Keene, Margaret E. Flanagan, Laura S. Hemmy, Kelvin O. Lim, Lon R. White, Kathleen S. Montine, Thomas J. Montine*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Two population-based studies key to advancing knowledge of brain aging are the Honolulu-Asia Aging Study (HAAS) and the Nun Study. Harmonization of their neuropathologic data allows cross comparison, with findings common to both studies likely generalizable, while distinct observations may point to aging brain changes that are dependent on sex, ethnicity, environment, or lifestyle factors. Here, we expanded the neuropathologic evaluation of these 2 studies using revised NIA-Alzheimer's Association guidelines and compared directly the neuropathologic features of resistance and apparent cognitive resilience. There were significant differences in prevalence of Alzheimer disease neuropathologic change, small vessel vascular brain injury, and Lewy body disease between these 2 studies, suggesting that sex, ethnicity, and lifestyle factors may significantly influence resistance to developing brain injury with age. In contrast, hippocampal sclerosis prevalence was very similar, but skewed to poorer cognitive performance, suggesting that hippocampal sclerosis could act sequentially with other diseases to impair cognitive function. Strikingly, despite these observed differences, the proportion of individuals resistant to all 4 diseases of brain or displaying apparent cognitive resilience was virtually identical between HAAS and Nun Study participants. Future in vivo validation of these results awaits comprehensive biomarkers of these 4 brain diseases.

Original languageEnglish (US)
Pages (from-to)458-466
Number of pages9
JournalJournal of neuropathology and experimental neurology
Volume76
Issue number6
DOIs
StatePublished - Jun 1 2017

Keywords

  • Alzheimer disease neuropathologic change
  • Cognitive resilience
  • NIA-AA guidelines
  • Population-based cohort

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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