DOI: 10.1101/508820Dec 31, 2018Paper

Identifying Changepoints in Biomarkers During the Preclinical Phase of AD

BioRxiv : the Preprint Server for Biology
Laurent YounesMichael I Miller


Objective: Several models have been proposed for the evolution of Alzheimer's disease (AD) biomarkers. The aim of this study was to identify changepoints in a range of biomarkers during the preclinical phase of AD. Methods: We examined nine measures based on cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) and cognitive testing, obtained from 306 cognitively normal individuals, a subset of whom subsequently progressed to the symptomatic phase of AD. A changepoint model was used to determine which of the measures had a significant change in slope in relation to clinical symptom onset. Results: All nine measures had significant changepoints, all of which preceded symptom onset, however the timing of these changepoints varied considerably. A single measure, CSF-tau, had an early changepoint (40 years prior to symptom onset). A group of measures, including the remaining CSF measures (CSF-Abeta and phosphorylated tau) and all cognitive tests had changepoints 10-15 years prior to symptom onset. A second group is formed by medial temporal lobe shape composite measures, with a five-year time difference between the right and left side (respectively nine and three years prior to symptom onset). Conclusions: These findings high...Continue Reading

Related Concepts

Alzheimer's Disease
Biological Markers
Cerebrospinal Fluid
Magnetic Resonance Imaging
Temporal Lobe
Granulocyte Colony-Stimulating Factor

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