Role of β-Amyloidosis and Neurodegeneration in Subsequent Imaging Changes in Mild Cognitive Impairment

David S. Knopman; Clifford R. Jack; Emily S. Lundt; Heather J. Wiste; Stephen D. Weigand; Prashanthi Vemuri; Val J. Lowe; Kejal Kantarci; Jeffrey L. Gunter; Matthew L. Senjem; Michelle M. Mielke; Mary M. Machulda; Rosebud O. Roberts; Bradley F. Boeve; David T. Jones; Ronald C. Petersen

doi:10.1001/jamaneurol.2015.2323

Role of β-Amyloidosis and Neurodegeneration in Subsequent Imaging Changes in Mild Cognitive Impairment

David S. Knopman, Clifford R. Jack, Emily S. Lundt, Heather J. Wiste, Stephen D. Weigand, Prashanthi Vemuri, Val J. Lowe, Kejal Kantarci, Jeffrey L. Gunter, Matthew L. Senjem, Michelle M. Mielke, Mary M. Machulda, Rosebud O. Roberts, Bradley F. Boeve, David T. Jones, Ronald C. Petersen

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

IMPORTANCE: To understand how a model of Alzheimer disease pathophysiology based on β-amyloidosis and neurodegeneration predicts the regional anatomic expansion of hypometabolism and atrophy in persons with mild cognitive impairment (MCI). OBJECTIVE: To define the role of β-amyloidosis and neurodegeneration in the subsequent progression of topographic cortical structural and metabolic changes in MCI. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal, observational study with serial brain imaging conducted from March 28, 2006, to January6, 2015, using a population-based cohort. A total of 96 participants with MCI (all aged >70 years) with serial imaging biomarkers from the Mayo Clinic Study of Aging or Mayo Alzheimer's Disease Research Center were included. Participants were characterized initially as having elevated or not elevated brain β-amyloidosis (A+ or A-) based on ¹¹C-Pittsburgh compound B positron emission tomography. They were further characterized initially by the presence or absence of neurodegeneration (N+or N-), where the presence of neurodegeneration was defined by abnormally low hippocampal volume or hypometabolism in an Alzheimer disease-like pattern on ¹⁸fluorodeoxyglucose (FDG)-positron emission tomography. MAIN OUTCOMES AND MEASURES: Regional FDG standardized uptake value ratio (SUVR) and gray matter volumes in medial temporal, lateral temporal, lateral parietal, and medial parietal regions. RESULTS: In the primary regions of interest (ROI), the A+N+ group (n = 45) had lower FDG SUVR at baseline compared with the A+N-group (n = 17) (all 4 ROIs; P

Original language	English (US)
Pages (from-to)	1475-1483
Number of pages	9
Journal	JAMA Neurology
Volume	72
Issue number	12
DOIs	https://doi.org/10.1001/jamaneurol.2015.2323
State	Published - Dec 1 2015
Externally published	Yes

ASJC Scopus subject areas

Clinical Neurology

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Knopman, D. S., Jack, C. R., Lundt, E. S., Wiste, H. J., Weigand, S. D., Vemuri, P., Lowe, V. J., Kantarci, K., Gunter, J. L., Senjem, M. L., Mielke, M. M., Machulda, M. M., Roberts, R. O., Boeve, B. F., Jones, D. T., & Petersen, R. C. (2015). Role of β-Amyloidosis and Neurodegeneration in Subsequent Imaging Changes in Mild Cognitive Impairment. JAMA Neurology, 72(12), 1475-1483. https://doi.org/10.1001/jamaneurol.2015.2323

Knopman, DS, Jack, CR, Lundt, ES, Wiste, HJ, Weigand, SD, Vemuri, P, Lowe, VJ, Kantarci, K, Gunter, JL, Senjem, ML, Mielke, MM, Machulda, MM, Roberts, RO, Boeve, BF, Jones, DT & Petersen, RC 2015, 'Role of β-Amyloidosis and Neurodegeneration in Subsequent Imaging Changes in Mild Cognitive Impairment', JAMA Neurology, vol. 72, no. 12, pp. 1475-1483. https://doi.org/10.1001/jamaneurol.2015.2323

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title = "Role of β-Amyloidosis and Neurodegeneration in Subsequent Imaging Changes in Mild Cognitive Impairment",

abstract = "IMPORTANCE: To understand how a model of Alzheimer disease pathophysiology based on β-amyloidosis and neurodegeneration predicts the regional anatomic expansion of hypometabolism and atrophy in persons with mild cognitive impairment (MCI). OBJECTIVE: To define the role of β-amyloidosis and neurodegeneration in the subsequent progression of topographic cortical structural and metabolic changes in MCI. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal, observational study with serial brain imaging conducted from March 28, 2006, to January6, 2015, using a population-based cohort. A total of 96 participants with MCI (all aged >70 years) with serial imaging biomarkers from the Mayo Clinic Study of Aging or Mayo Alzheimer's Disease Research Center were included. Participants were characterized initially as having elevated or not elevated brain β-amyloidosis (A+ or A-) based on 11C-Pittsburgh compound B positron emission tomography. They were further characterized initially by the presence or absence of neurodegeneration (N+or N-), where the presence of neurodegeneration was defined by abnormally low hippocampal volume or hypometabolism in an Alzheimer disease-like pattern on 18fluorodeoxyglucose (FDG)-positron emission tomography. MAIN OUTCOMES AND MEASURES: Regional FDG standardized uptake value ratio (SUVR) and gray matter volumes in medial temporal, lateral temporal, lateral parietal, and medial parietal regions. RESULTS: In the primary regions of interest (ROI), the A+N+ group (n = 45) had lower FDG SUVR at baseline compared with the A+N-group (n = 17) (all 4 ROIs; P ",

author = "Knopman, {David S.} and Jack, {Clifford R.} and Lundt, {Emily S.} and Wiste, {Heather J.} and Weigand, {Stephen D.} and Prashanthi Vemuri and Lowe, {Val J.} and Kejal Kantarci and Gunter, {Jeffrey L.} and Senjem, {Matthew L.} and Mielke, {Michelle M.} and Machulda, {Mary M.} and Roberts, {Rosebud O.} and Boeve, {Bradley F.} and Jones, {David T.} and Petersen, {Ronald C.}",

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doi = "10.1001/jamaneurol.2015.2323",

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T1 - Role of β-Amyloidosis and Neurodegeneration in Subsequent Imaging Changes in Mild Cognitive Impairment

AU - Knopman, David S.

AU - Jack, Clifford R.

AU - Lundt, Emily S.

AU - Wiste, Heather J.

AU - Weigand, Stephen D.

AU - Vemuri, Prashanthi

AU - Lowe, Val J.

AU - Kantarci, Kejal

AU - Gunter, Jeffrey L.

AU - Senjem, Matthew L.

AU - Mielke, Michelle M.

AU - Machulda, Mary M.

AU - Roberts, Rosebud O.

AU - Boeve, Bradley F.

AU - Jones, David T.

AU - Petersen, Ronald C.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - IMPORTANCE: To understand how a model of Alzheimer disease pathophysiology based on β-amyloidosis and neurodegeneration predicts the regional anatomic expansion of hypometabolism and atrophy in persons with mild cognitive impairment (MCI). OBJECTIVE: To define the role of β-amyloidosis and neurodegeneration in the subsequent progression of topographic cortical structural and metabolic changes in MCI. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal, observational study with serial brain imaging conducted from March 28, 2006, to January6, 2015, using a population-based cohort. A total of 96 participants with MCI (all aged >70 years) with serial imaging biomarkers from the Mayo Clinic Study of Aging or Mayo Alzheimer's Disease Research Center were included. Participants were characterized initially as having elevated or not elevated brain β-amyloidosis (A+ or A-) based on 11C-Pittsburgh compound B positron emission tomography. They were further characterized initially by the presence or absence of neurodegeneration (N+or N-), where the presence of neurodegeneration was defined by abnormally low hippocampal volume or hypometabolism in an Alzheimer disease-like pattern on 18fluorodeoxyglucose (FDG)-positron emission tomography. MAIN OUTCOMES AND MEASURES: Regional FDG standardized uptake value ratio (SUVR) and gray matter volumes in medial temporal, lateral temporal, lateral parietal, and medial parietal regions. RESULTS: In the primary regions of interest (ROI), the A+N+ group (n = 45) had lower FDG SUVR at baseline compared with the A+N-group (n = 17) (all 4 ROIs; P

AB - IMPORTANCE: To understand how a model of Alzheimer disease pathophysiology based on β-amyloidosis and neurodegeneration predicts the regional anatomic expansion of hypometabolism and atrophy in persons with mild cognitive impairment (MCI). OBJECTIVE: To define the role of β-amyloidosis and neurodegeneration in the subsequent progression of topographic cortical structural and metabolic changes in MCI. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal, observational study with serial brain imaging conducted from March 28, 2006, to January6, 2015, using a population-based cohort. A total of 96 participants with MCI (all aged >70 years) with serial imaging biomarkers from the Mayo Clinic Study of Aging or Mayo Alzheimer's Disease Research Center were included. Participants were characterized initially as having elevated or not elevated brain β-amyloidosis (A+ or A-) based on 11C-Pittsburgh compound B positron emission tomography. They were further characterized initially by the presence or absence of neurodegeneration (N+or N-), where the presence of neurodegeneration was defined by abnormally low hippocampal volume or hypometabolism in an Alzheimer disease-like pattern on 18fluorodeoxyglucose (FDG)-positron emission tomography. MAIN OUTCOMES AND MEASURES: Regional FDG standardized uptake value ratio (SUVR) and gray matter volumes in medial temporal, lateral temporal, lateral parietal, and medial parietal regions. RESULTS: In the primary regions of interest (ROI), the A+N+ group (n = 45) had lower FDG SUVR at baseline compared with the A+N-group (n = 17) (all 4 ROIs; P

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Role of β-Amyloidosis and Neurodegeneration in Subsequent Imaging Changes in Mild Cognitive Impairment

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