TY - JOUR
T1 - Relationship between Amyloid-β positivity and progression to mild cognitive impairment or dementia over 8 years in cognitively normal older adults
AU - Dang, Christa
AU - Harrington, Karra D.
AU - Lim, Yen Ying
AU - Ames, David
AU - Hassenstab, Jason
AU - Laws, Simon M.
AU - Yassi, Nawaf
AU - Hickey, Martha
AU - Rainey-Smith, Stephanie
AU - Robertson, Joanne
AU - Sohrabi, Hamid R.
AU - Salvado, Olivier
AU - Weinborn, Michael
AU - Villemagne, Victor L.
AU - Rowe, Christopher C.
AU - Masters, Colin L.
AU - Maruff, Paul
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - APOE ϵ4
KW - biomarkers
KW - dementia
KW - mild cognitive impairment
UR - http://www.scopus.com/inward/record.url?scp=85054127969&partnerID=8YFLogxK
U2 - 10.3233/JAD-180507
DO - 10.3233/JAD-180507
M3 - Article
C2 - 30149452
AN - SCOPUS:85054127969
SN - 1387-2877
VL - 65
SP - 1313
EP - 1325
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 4
ER -