Alzheimer disease pathology in subjects without dementia in 2 studies of aging: The nun study and the adult changes in thought study

Karen S. Santacruz, Joshua A. Sonnen, Maryam Kherad Pezhouh, Mark F. Desrosiers, Peter T. Nelson, Suzanne L. Tyas

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


Individuals with antemortem preservation of cognition who show autopsy evidence of at least moderate Alzheimer disease (AD) pathology suggest the possibility of brain reserve, that is, functional resistance to structural brain damage. This reserve would, however, only be relevant if the pathologic markers correlate well with dementia. Using data from the Nun Study (n = 498) and the Adult Changes in Thought (ACT) Study (n = 323), we show that Braak staging correlates strongly with dementia status. Moreover, participants with severe(Braak stage V-VI) AD pathology who remained not demented represent only 12% (Nun Study) and 8% (ACT study) of nondemented subjects. Comparison of these subjects to those who were demented revealed that the former group was often significantly memory-impaired despite not being classified as demented. Most of these nondemented participants showed only stage V neurofibrillary pathology and frontal tangle counts that were slightly lower than a comparable (Braak stage V) dementia group. In summary, these data indicate that, in individuals with AD-type pathology who do not meet criteria for dementia, neocortical neurofibrillary tangles are somewhat reduced and incipient cognitive decline is present. Our data provide a foundation for helping to define additional factors that may impair, or be protective of, cognition in older adults.

Original languageEnglish (US)
Pages (from-to)832-840
Number of pages9
JournalJournal of neuropathology and experimental neurology
Issue number10
StatePublished - Oct 2011
Externally publishedYes


  • Adult Changes in Thought study
  • Alzheimer disease
  • Brain reserve
  • Dementia
  • Nun Study
  • Preclinical
  • Presymptomatic

ASJC Scopus subject areas

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


Dive into the research topics of 'Alzheimer disease pathology in subjects without dementia in 2 studies of aging: The nun study and the adult changes in thought study'. Together they form a unique fingerprint.

Cite this