Identifying changepoints in biomarkers during the preclinical phase of Alzheimer's disease

Laurent Younes, Marilyn Albert, Abhay R Moghekar, Anja Soldan, Corinne Pettigrew, Michael I. Miller

Research output: Contribution to journalArticle

Abstract

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 t-tau, had an early changepoint (34 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 6-year time difference between the right and left side (respectively nine and 3 years prior to symptom onset). Conclusion: These findings highlight the long period of time prior to symptom onset during which AD pathology is accumulating in the brain. There are several significant findings, including the early changes in cognition and the laterality of the MRI findings. Additional work is needed to clarify their significance.

Original languageEnglish (US)
Article number74
JournalFrontiers in Aging Neuroscience
Volume11
Issue numberAPR
DOIs
StatePublished - Jan 1 2019

Fingerprint

Cerebrospinal Fluid
Alzheimer Disease
Biomarkers
Magnetic Resonance Imaging
Temporal Lobe
Cognition
Pathology
Brain

Keywords

  • Biomarkers
  • Changepoints
  • Cognitive assessment
  • CSF assessment
  • Preclinical Alzheimer's disease
  • Shape analysis

ASJC Scopus subject areas

  • Aging
  • Cognitive Neuroscience

Cite this

Identifying changepoints in biomarkers during the preclinical phase of Alzheimer's disease. / Younes, Laurent; Albert, Marilyn; Moghekar, Abhay R; Soldan, Anja; Pettigrew, Corinne; Miller, Michael I.

In: Frontiers in Aging Neuroscience, Vol. 11, No. APR, 74, 01.01.2019.

Research output: Contribution to journalArticle

@article{d07402d3cb504f8e8578a2d047ae0446,
title = "Identifying changepoints in biomarkers during the preclinical phase of Alzheimer's disease",
abstract = "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 t-tau, had an early changepoint (34 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 6-year time difference between the right and left side (respectively nine and 3 years prior to symptom onset). Conclusion: These findings highlight the long period of time prior to symptom onset during which AD pathology is accumulating in the brain. There are several significant findings, including the early changes in cognition and the laterality of the MRI findings. Additional work is needed to clarify their significance.",
keywords = "Biomarkers, Changepoints, Cognitive assessment, CSF assessment, Preclinical Alzheimer's disease, Shape analysis",
author = "Laurent Younes and Marilyn Albert and Moghekar, {Abhay R} and Anja Soldan and Corinne Pettigrew and Miller, {Michael I.}",
year = "2019",
month = "1",
day = "1",
doi = "10.3389/fnagi.2019.00074",
language = "English (US)",
volume = "11",
journal = "Frontiers in Aging Neuroscience",
issn = "1663-4365",
publisher = "Frontiers Research Foundation",
number = "APR",

}

TY - JOUR

T1 - Identifying changepoints in biomarkers during the preclinical phase of Alzheimer's disease

AU - Younes, Laurent

AU - Albert, Marilyn

AU - Moghekar, Abhay R

AU - Soldan, Anja

AU - Pettigrew, Corinne

AU - Miller, Michael I.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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 t-tau, had an early changepoint (34 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 6-year time difference between the right and left side (respectively nine and 3 years prior to symptom onset). Conclusion: These findings highlight the long period of time prior to symptom onset during which AD pathology is accumulating in the brain. There are several significant findings, including the early changes in cognition and the laterality of the MRI findings. Additional work is needed to clarify their significance.

AB - 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 t-tau, had an early changepoint (34 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 6-year time difference between the right and left side (respectively nine and 3 years prior to symptom onset). Conclusion: These findings highlight the long period of time prior to symptom onset during which AD pathology is accumulating in the brain. There are several significant findings, including the early changes in cognition and the laterality of the MRI findings. Additional work is needed to clarify their significance.

KW - Biomarkers

KW - Changepoints

KW - Cognitive assessment

KW - CSF assessment

KW - Preclinical Alzheimer's disease

KW - Shape analysis

UR - http://www.scopus.com/inward/record.url?scp=85068251638&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85068251638&partnerID=8YFLogxK

U2 - 10.3389/fnagi.2019.00074

DO - 10.3389/fnagi.2019.00074

M3 - Article

C2 - 31001108

AN - SCOPUS:85068251638

VL - 11

JO - Frontiers in Aging Neuroscience

JF - Frontiers in Aging Neuroscience

SN - 1663-4365

IS - APR

M1 - 74

ER -