Title

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

Document Type

Journal Article

Publication Title

Journal of Alzheimer's disease : JAD

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 Exercise, Biomedical and Health Sciences

RAS ID

27293

Comments

Originally published as: 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. Original article available here.

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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