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 language | English (US) |
|---|---|
| Article number | 74 |
| Journal | Frontiers in Aging Neuroscience |
| Volume | 11 |
| Issue number | APR |
| DOIs | |
| State | Published - Jan 1 2019 |
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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 journal › Article
}
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 -