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 journalArticle

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
Externally publishedYes

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