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

2018

Dang, Christa

Harrington, Karra D

Lim, Yen Ying

Ames, David

Hassenstab, Jason

Laws, Simon M

Yassi, Nawaf

Hickey, Martha

Rainey-Smith, Stephanie R

Robertson, Joanne

Sohrabi, Hamid R

Salvado, Olivier

Weinborn, Michael

Villemagne, Victor L

Rowe, Christopher C

Masters, Colin L

Maruff, Paul

APOEɛ4

Alzheimer’s disease

biomarkers

dementia

mild cognitive impairment

Journal Article

0000-0003-3910-2453

10.3233/JAD-180507

Preclinical Alzheimer's disease (AD) is defined by cerebral amyloid-β positivity (Aβ+) in cognitively normal (CN) older adults. 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. 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. 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. 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.

link

Journal of Alzheimer's disease : JAD 2018; 65(4): 1313-1325

Journal of Alzheimer's disease : JAD