Ivan Koychev1, Nemanja Vaci1, Murat Bilgel2, Yang An2, Graciela Terrera Muniz3, Dean F Wong4, John Gallacher1, Abhay Mogekhar5, Marilyn Albert5, Susan M Resnick2. 1. Department of Psychiatry University of Oxford Oxford UK. 2. Laboratory of Behavioral Neuroscience National Institute on Aging National Institutes of Health Baltimore Maryland. 3. Centre for Dementia Prevention The University of Edinburgh Edinburgh UK. 4. Department of Radiology Johns Hopkins School of Medicine Baltimore Maryland. 5. Department of Neurology Johns Hopkins School of Medicine Baltimore Maryland.
Abstract
Objective: To test the hypothesis that among cognitively healthy individuals, distinct groups exist in terms of amyloid and phosphorylated-tau accumulation rates; that if rapid accumulator groups exist, their membership can be predicted by Alzheimer's disease (AD) risk factors, and that time points of significant increase in AD protein accumulation will be evident. Methods: The analysis reports data from 263 individuals from the BIOCARD and 184 individuals from the Baltimore Longitudinal Study of Aging with repeated cerebrospinal fluid (CSF) and positron emission tomography (PET) sampling, respectively. We used latent class mixed-effect models to identify distinct classes of amyloid (CSF and PET) and p-Tau (CSF) accumulation rates and generalized additive modeling to investigate non-linear changes to AD biomarkers. Results: For both amyloid and p-Tau latent class models we confirmed the existence of two separate classes: accumulators and non-accumulators. The accumulator and non-accumulator groups differed significantly in terms of baseline AD protein levels and slope of change. APOE ε4 carrier status and episodic memory predicted amyloid class membership. Non-linear models revealed time points of significant increase in the rate of amyloid and p-Tau accumulation whereby APOE ε4 carrier status associated with earlier age at onset of rapid accumulation. Conclusions: The current analysis demonstrates the existence of distinct classes of amyloid and p-Tau accumulators. Predictors of class membership were identified but the overall accuracy of the models was modest, highlighting the need for additional biomarkers that are sensitive to early disease phenotypes.
Objective: To test the hypothesis that among cognitively healthy individuals, distinct groups exist in terms of amyloid and phosphorylated-tau accumulation rates; that if rapid accumulator groups exist, their membership can be predicted by Alzheimer's disease (AD) risk factors, and that time points of significant increase in AD protein accumulation will be evident. Methods: The analysis reports data from 263 individuals from the BIOCARD and 184 individuals from the Baltimore Longitudinal Study of Aging with repeated cerebrospinal fluid (CSF) and positron emission tomography (PET) sampling, respectively. We used latent class mixed-effect models to identify distinct classes of amyloid (CSF and PET) and p-Tau (CSF) accumulation rates and generalized additive modeling to investigate non-linear changes to AD biomarkers. Results: For both amyloid and p-Tau latent class models we confirmed the existence of two separate classes: accumulators and non-accumulators. The accumulator and non-accumulator groups differed significantly in terms of baseline AD protein levels and slope of change. APOE ε4 carrier status and episodic memory predicted amyloid class membership. Non-linear models revealed time points of significant increase in the rate of amyloid and p-Tau accumulation whereby APOE ε4 carrier status associated with earlier age at onset of rapid accumulation. Conclusions: The current analysis demonstrates the existence of distinct classes of amyloid and p-Tau accumulators. Predictors of class membership were identified but the overall accuracy of the models was modest, highlighting the need for additional biomarkers that are sensitive to early disease phenotypes.
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