Shapes of the trajectories of 5 major biomarkers of Alzheimer disease

Clifford R Jr. Jack, Prashanthi D Vemuri, Heather J. Wiste, Stephen D. Weigand, Timothy G. Lesnick, Val Lowe, Kejal M Kantarci, Matthew A Bernstein, Matthew L. Senjem, Jeffrey L. Gunter, Bradley F Boeve, John Q. Trojanowski, Leslie M. Shaw, Paul S. Aisen, Michael W. Weiner, Ronald Carl Petersen, David S Knopman

Research output: Contribution to journalArticle

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Abstract

Objective: To characterize the shape of the trajectories of Alzheimer disease biomarkers as a function of Mini-Mental State Examination (MMSE) score. Design and Setting: Longitudinal registries from the Mayo Clinic and the Alzheimer's Disease Neuroimaging Initiative. Patients: Two different samples (n = 343 and n = 598) were created that spanned the cognitive spectrum from normal to Alzheimer disease dementia. Subgroup analyses were performed in members of both cohorts (n = 243 and n = 328) who were amyloid positive at baseline. Main Outcome Measures: The shape of biomarker trajectories as a function of MMSE score, adjusted for age, was modeled and described as baseline (crosssectional) and within-subject longitudinal effects. Biomarkers evaluated were cerebrospinal fluid (CSF) Aβ42 and tau levels, amyloid and fluorodeoxyglucose positron emission tomography imaging, and structural magnetic resonance imaging. Results: Baseline biomarker values generally worsened (ie, nonzero slope) with lower baseline MMSE score. Baseline hippocampal volume, amyloid positron emission tomography, and fluorodeoxyglucose positron emission tomography values plateaued (ie, nonlinear slope) with lower MMSE score in 1 or more analyses. Longitudinally, within-subject rates of biomarker change were associated with worsening MMSE score. Nonconstant within-subject rates (deceleration) of biomarker change were found in only 1 model. Conclusions: Biomarker trajectory shapes by MMSE score were complex and were affected by interactions with age and APOE status. Nonlinearity was found in several baseline effects models. Nonconstant within-subject rates of biomarker change were found in only 1 model, likely owing to limited within-subject longitudinal follow-up. Creating reliable models that describe the full trajectories of Alzheimer disease biomarkers will require significant additional longitudinal data in individual participants.

Original languageEnglish (US)
Pages (from-to)856-867
Number of pages12
JournalArchives of Neurology
Volume69
Issue number7
DOIs
StatePublished - Jul 2012

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Alzheimer Disease
Biomarkers
Amyloid
Positron-Emission Tomography
Alzheimer's Disease
Trajectory
Deceleration
Neuroimaging
Cerebrospinal Fluid
Registries
Mental State
Magnetic Resonance Imaging
Outcome Assessment (Health Care)
Positron Emission Tomography

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Shapes of the trajectories of 5 major biomarkers of Alzheimer disease. / Jack, Clifford R Jr.; Vemuri, Prashanthi D; Wiste, Heather J.; Weigand, Stephen D.; Lesnick, Timothy G.; Lowe, Val; Kantarci, Kejal M; Bernstein, Matthew A; Senjem, Matthew L.; Gunter, Jeffrey L.; Boeve, Bradley F; Trojanowski, John Q.; Shaw, Leslie M.; Aisen, Paul S.; Weiner, Michael W.; Petersen, Ronald Carl; Knopman, David S.

In: Archives of Neurology, Vol. 69, No. 7, 07.2012, p. 856-867.

Research output: Contribution to journalArticle

Jack, Clifford R Jr. ; Vemuri, Prashanthi D ; Wiste, Heather J. ; Weigand, Stephen D. ; Lesnick, Timothy G. ; Lowe, Val ; Kantarci, Kejal M ; Bernstein, Matthew A ; Senjem, Matthew L. ; Gunter, Jeffrey L. ; Boeve, Bradley F ; Trojanowski, John Q. ; Shaw, Leslie M. ; Aisen, Paul S. ; Weiner, Michael W. ; Petersen, Ronald Carl ; Knopman, David S. / Shapes of the trajectories of 5 major biomarkers of Alzheimer disease. In: Archives of Neurology. 2012 ; Vol. 69, No. 7. pp. 856-867.
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abstract = "Objective: To characterize the shape of the trajectories of Alzheimer disease biomarkers as a function of Mini-Mental State Examination (MMSE) score. Design and Setting: Longitudinal registries from the Mayo Clinic and the Alzheimer's Disease Neuroimaging Initiative. Patients: Two different samples (n = 343 and n = 598) were created that spanned the cognitive spectrum from normal to Alzheimer disease dementia. Subgroup analyses were performed in members of both cohorts (n = 243 and n = 328) who were amyloid positive at baseline. Main Outcome Measures: The shape of biomarker trajectories as a function of MMSE score, adjusted for age, was modeled and described as baseline (crosssectional) and within-subject longitudinal effects. Biomarkers evaluated were cerebrospinal fluid (CSF) Aβ42 and tau levels, amyloid and fluorodeoxyglucose positron emission tomography imaging, and structural magnetic resonance imaging. Results: Baseline biomarker values generally worsened (ie, nonzero slope) with lower baseline MMSE score. Baseline hippocampal volume, amyloid positron emission tomography, and fluorodeoxyglucose positron emission tomography values plateaued (ie, nonlinear slope) with lower MMSE score in 1 or more analyses. Longitudinally, within-subject rates of biomarker change were associated with worsening MMSE score. Nonconstant within-subject rates (deceleration) of biomarker change were found in only 1 model. Conclusions: Biomarker trajectory shapes by MMSE score were complex and were affected by interactions with age and APOE status. Nonlinearity was found in several baseline effects models. Nonconstant within-subject rates of biomarker change were found in only 1 model, likely owing to limited within-subject longitudinal follow-up. Creating reliable models that describe the full trajectories of Alzheimer disease biomarkers will require significant additional longitudinal data in individual participants.",
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AU - Vemuri, Prashanthi D

AU - Wiste, Heather J.

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AU - Lesnick, Timothy G.

AU - Lowe, Val

AU - Kantarci, Kejal M

AU - Bernstein, Matthew A

AU - Senjem, Matthew L.

AU - Gunter, Jeffrey L.

AU - Boeve, Bradley F

AU - Trojanowski, John Q.

AU - Shaw, Leslie M.

AU - Aisen, Paul S.

AU - Weiner, Michael W.

AU - Petersen, Ronald Carl

AU - Knopman, David S

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N2 - Objective: To characterize the shape of the trajectories of Alzheimer disease biomarkers as a function of Mini-Mental State Examination (MMSE) score. Design and Setting: Longitudinal registries from the Mayo Clinic and the Alzheimer's Disease Neuroimaging Initiative. Patients: Two different samples (n = 343 and n = 598) were created that spanned the cognitive spectrum from normal to Alzheimer disease dementia. Subgroup analyses were performed in members of both cohorts (n = 243 and n = 328) who were amyloid positive at baseline. Main Outcome Measures: The shape of biomarker trajectories as a function of MMSE score, adjusted for age, was modeled and described as baseline (crosssectional) and within-subject longitudinal effects. Biomarkers evaluated were cerebrospinal fluid (CSF) Aβ42 and tau levels, amyloid and fluorodeoxyglucose positron emission tomography imaging, and structural magnetic resonance imaging. Results: Baseline biomarker values generally worsened (ie, nonzero slope) with lower baseline MMSE score. Baseline hippocampal volume, amyloid positron emission tomography, and fluorodeoxyglucose positron emission tomography values plateaued (ie, nonlinear slope) with lower MMSE score in 1 or more analyses. Longitudinally, within-subject rates of biomarker change were associated with worsening MMSE score. Nonconstant within-subject rates (deceleration) of biomarker change were found in only 1 model. Conclusions: Biomarker trajectory shapes by MMSE score were complex and were affected by interactions with age and APOE status. Nonlinearity was found in several baseline effects models. Nonconstant within-subject rates of biomarker change were found in only 1 model, likely owing to limited within-subject longitudinal follow-up. Creating reliable models that describe the full trajectories of Alzheimer disease biomarkers will require significant additional longitudinal data in individual participants.

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