The Spectrum of Alzheimer-Type Pathology in Cognitively Normal Individuals

Jamie M. Walker, Shiva Kazempour Dehkordi, Jeff Schaffert, William Goette, Charles L. White, Timothy E. Richardson, Habil Zare

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Background: The strongest risk factor for the development of Alzheimer's disease (AD) is age. The progression of Braak stage and Thal phase with age has been demonstrated. However, prior studies did not include cognitive status. Objective: We set out to define normative values for Alzheimer-Type pathologic changes in individuals without cognitive decline, and then define levels that would qualify them to be resistant to or resilient against these changes. Methods: Utilizing neuropathology data obtained from the National Alzheimer's Coordinating Center (NACC), we demonstrate the age-related progression of Alzheimer-Type pathologic changes in cognitively normal individuals (CDR=0, n=542). With plots generated from these data, we establish standard lines that may be utilized to measure the extent to which an individual's Alzheimer-Type pathology varies from the estimated normal range of pathology. Results: Although Braak stage and Thal phase progressively increase with age in cognitively normal individuals, the Consortium to Establish a Registry for Alzheimer's Disease neuritic plaque score and Alzheimer's disease neuropathologic change remain at low levels. Conclusion: These findings suggest that an increasing burden of neuritic plaques is a strong predictor of cognitive decline, whereas, neurofibrillary degeneration and amyloid-β (diffuse) plaque deposition, both to some degree, are normal pathologic changes of aging that occur in almost all individuals regardless of cognitive status. Furthermore, we have defined the amount of neuropathologic change in cognitively normal individuals that would qualify them to be 'resilient' against the pathology (significantly above the normative values for age, but still cognitively normal) or 'resistant' to the development of pathology (significantly below the normative values for age).

Original languageEnglish (US)
Pages (from-to)683-695
Number of pages13
JournalJournal of Alzheimer's Disease
Volume91
Issue number2
DOIs
StatePublished - 2023

Keywords

  • Alzheimer's disease
  • Braak stage
  • CERAD neuritic plaque score
  • Thal phase
  • cognitively normal
  • resilience
  • resistance

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Clinical Psychology
  • General Neuroscience

Fingerprint

Dive into the research topics of 'The Spectrum of Alzheimer-Type Pathology in Cognitively Normal Individuals'. Together they form a unique fingerprint.

Cite this