Relationship between Amyloid-β Positivity and Progression to Mild Cognitive Impairment or Dementia over 8 Years in Cognitively Normal Older Adults

Christa Dang, Karra D. Harrington, Yen Ying Lim, David Ames, Jason Hassenstab, Simon M. Laws, Nawaf Yassi, Martha Hickey, Stephanie Rainey-Smith, Joanne Robertson, Hamid R. Sohrabi, Olivier Salvado, Michael Weinborn, Victor L. Villemagne, Christopher C. Rowe, Colin L. Masters, Paul Maruff

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Abstract

Background: Preclinical Alzheimer's disease (AD) is defined by cerebral amyloid-β positivity (A+β) in cognitively normal (CN) older adults. Objective: To estimate the risk of progression to the symptomatic stages of AD due to PET Aβ+ and the extent that progression was influenced by other demographic, genetic, and clinical characteristics in a large prospective study. Methods: Fine-Gray subdistribution modeling was used to examine the risk of progression from CN to MCI/dementia due to A+, APOE ϵ4 carriage, and their interaction in the Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging CN cohort (n = 599) over 8 years. Results: 17.7% A+ and 8.1% A-progressed over 8 years (OR: 2.43). Risk of progression for A+ was 65-104% greater than A-. A+ APOE ϵ4 carriers were at 348% greater risk than all other participants. Significant risk factors of progression in A+ were age (HR: 1.05), PET SUVR (HR: 2.49) and APOE ϵ4 carriage (HR: 2.63); only age was a significant risk factor in A-(HR: 1.09). A-progressors were not near the threshold for A+. These relationships were not moderated by hypertension, diabetes, obesity, or stroke/TIA. Conclusion: A+ is an important prognostic marker for progression from CN to MCI/dementia in older adults and APOE ϵ4 carriage provides further predictive value in the presence of A+. These data suggest that A-associated clinical progression is consistent with clinical-pathological models of AD, whereas progression in the absence of elevated A deposition may be the result of neuropathological processes other than AD that accumulate with age.

Original languageEnglish
Pages (from-to)1313-1325
Number of pages13
JournalJournal of Alzheimer's Disease
Volume65
Issue number4
DOIs
StatePublished - Jan 1 2018

Keywords

  • APOE ϵ4
  • Alzheimer's disease
  • biomarkers
  • dementia
  • mild cognitive impairment

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    Dang, C., Harrington, K. D., Lim, Y. Y., Ames, D., Hassenstab, J., Laws, S. M., Yassi, N., Hickey, M., Rainey-Smith, S., Robertson, J., Sohrabi, H. R., Salvado, O., Weinborn, M., Villemagne, V. L., Rowe, C. C., Masters, C. L., & Maruff, P. (2018). Relationship between Amyloid-β Positivity and Progression to Mild Cognitive Impairment or Dementia over 8 Years in Cognitively Normal Older Adults. Journal of Alzheimer's Disease, 65(4), 1313-1325. https://doi.org/10.3233/JAD-180507