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

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

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1475-1483
Number of pages9
JournalJAMA Neurology
Volume72
Issue number12
DOIs
StatePublished - Dec 1 2015

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Amyloidosis
Alzheimer Disease
Positron-Emission Tomography
Parietal Lobe
Neuroimaging
Atrophy
Observational Studies
Longitudinal Studies
Biomarkers
Brain
Research
Population
Cognitive Dysfunction

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Role of β-Amyloidosis and Neurodegeneration in Subsequent Imaging Changes in Mild Cognitive Impairment. / Knopman, David S; Jack, Clifford R Jr.; Lundt, Emily S.; Wiste, Heather J.; Weigand, Stephen D.; Vemuri, Prashanthi D; Lowe, Val; Kantarci, Kejal M; Gunter, Jeffrey L.; Senjem, Matthew L.; Mielke, Michelle M; Machulda, Mary Margaret; Roberts, Rosebud O; Boeve, Bradley F; Jones, David T; Petersen, Ronald Carl.

In: JAMA Neurology, Vol. 72, No. 12, 01.12.2015, p. 1475-1483.

Research output: Contribution to journalArticle

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AU - Knopman, David S

AU - Jack, Clifford R Jr.

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AU - Wiste, Heather J.

AU - Weigand, Stephen D.

AU - Vemuri, Prashanthi D

AU - Lowe, Val

AU - Kantarci, Kejal M

AU - Gunter, Jeffrey L.

AU - Senjem, Matthew L.

AU - Mielke, Michelle M

AU - Machulda, Mary Margaret

AU - Roberts, Rosebud O

AU - Boeve, Bradley F

AU - Jones, David T

AU - Petersen, Ronald Carl

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