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Relationship between amyloid-β positivity and progression to mild cognitive impairment or dementia over 8 years in cognitively normal older adults

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.ORCID: 0000-0001-8017-8682, Salvado, O., Weinborn, M., Villemagne, V.L., Rowe, C.C., Masters, C.L. and Maruff, Paul (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). pp. 1313-1325.

Link to Published Version: https://doi.org/10.3233/jad-180507
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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+, APOE ɛ4 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+ APOE ɛ4 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 APOE ɛ4 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.

Item Type: Journal Article
Publisher: IOS Press
URI: http://researchrepository.murdoch.edu.au/id/eprint/55614
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