Relationship between Amyloid-β positivity and progression to mild cognitive impairment or dementia over 8 years in cognitively nonrmal older adults
Authors
Christa Dang
Karra D Harrington
Yen Ying Lim
David Ames
Jason Hassenstab
Simon M. Laws, Edith Cowan UniversityFollow
Nawaf Yassi
Martha Hickey
Stephanie Rainey-Smith, Edith Cowan UniversityFollow
Joanne Robertson
Hamid R. Sohrabi, Edith Cowan UniversityFollow
Olivier Salvado
Michael Weinborn, Edith Cowan UniversityFollow
Victor L Villemagne
Christopher C Rowe
Colin L Masters
Paul Maruff
Document Type
Journal Article
Publication Title
Journal of Alzheimer's Disease
ISSN
1875-8908
Volume
65
Issue
4
First Page
1313
Last Page
1325
PubMed ID
30149452
Publisher
IOS Press
School
Centre of Excellence for Alzheimer's Disease Research and Care / School of Medical and Health Sciences
RAS ID
27293
Abstract
BACKGROUND: Preclinical Alzheimer's disease (AD) is defined by cerebral amyloid-β positivity (Aβ+) 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 Aβ+, APOEɛ4 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% Aβ+ and 8.1% Aβ-progressed over 8 years (OR: 2.43). Risk of progression for Aβ+ was 65-104% greater than Aβ-. Aβ+ APOEɛ4 carriers were at 348% greater risk than all other participants. Significant risk factors of progression in Aβ+ were age (HR: 1.05), PET SUVR (HR: 2.49) and APOE ɛ4 carriage (HR: 2.63); only age was a significant risk factor in Aβ-(HR: 1.09). Aβ-progressors were not near the threshold for Aβ+. These relationships were not moderated by hypertension, diabetes, obesity, or stroke/TIA.
CONCLUSION: Aβ+ is an important prognostic marker for progression from CN to MCI/dementia in older adults and APOEɛ4 carriage provides further predictive value in the presence of Aβ+. These data suggest that Aβ-associated clinical progression is consistent with clinical-pathological models of AD, whereas progression in the absence of elevated Aβ deposition may be the result of neuropathological processes other than AD that accumulate with age.
DOI
10.3233/JAD-180507
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Comments
Dang, C., Harrington, K. D., Lim, Y. Y., Ames, D., Hassenstab, J., Laws, S. M., ... & Sohrabi, H. R. (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, (Preprint), 1-13. Available here.