Relationship between Amyloid-β positivity and progression to mild cognitive impairment or dementia over 8 years in cognitively nonrmal older adults
Karra D Harrington
Yen Ying Lim
Simon M. Laws, Edith Cowan UniversityFollow
Stephanie Rainey-Smith, Edith Cowan UniversityFollow
Hamid R. Sohrabi, Edith Cowan UniversityFollow
Michael Weinborn, Edith Cowan UniversityFollow
Victor L Villemagne
Christopher C Rowe
Colin L Masters
Journal of Alzheimer's Disease
Centre of Excellence for Alzheimer's Disease Research and Care / School of Medical and Health Sciences
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.
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.