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Updated: Jun 9, 2025

Intracerebroventricular Injection of Amyloid-β Peptides in Normal Mice to Acutely Induce Alzheimer-like Cognitive Deficits
Published on: March 16, 2016
Latent change-on-change between amyloid accumulation and cognitive decline
Hannah M Klinger1, Brian C Healy1, Bernard J Hanseeuw2,3
1Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Introduction:
While the influence of cross-sectional β-amyloid (Aβ) on longitudinal changes in cognition is well established, longitudinal change-on-change between Aβ and cognition is less explored.
Methods:
A series of bivariate latent change score models (LCSM) examined the relationship between changes in 11C-Pittsburgh Compound-B (PiB) positron emission tomography (PET) and the Preclinical Alzheimer's Cognitive Composite-5 (PACC-5) while adjusting for covariates, including cross-sectional medial temporal lobe (MTL) tau-PET burden. We selected 352 clinically normal older participants with up to 9 years of PiB-PET and PACC-5 data from the Harvard Aging Brain Study (HABS).
Results:
Aβ accumulation was associated with subsequent cognitive decline beyond the effects of cross-sectional Aβ burden. Within this model including covariates such as age, sex, and apolipoprotein ε4 (APOEε4) status, we found no evidence supporting previously published associations between cross-sectional tau-PET and cognitive intercept/slope.
Discussion:
Short-term Aβ changes are significantly associated with cognitive decline in clinically normal older adults and may eclipse the effect of cross-sectional Aβ and MTL tau.
Highlights:
Aβ accumulation is associated with subsequent cognitive decline. High Aβ burden is not the sole metric signaling impending cognitive decline. Contrary to prior work, MTL tau-PET and cognition were not associated in our models. Models of bivariate latent Aβ and cognitive change may eclipse the effects of MTL tau.
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