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Published Online: 14 April 2020

Comparison of T1Rho MRI, Glucose Metabolism, and Amyloid Burden Across the Cognitive Spectrum: A Pilot Study

Publication: The Journal of Neuropsychiatry and Clinical Neurosciences

Abstract

Objective:

The pathological cascades associated with the development of Alzheimer’s disease (AD) have a common element: acidosis. T1rho MRI is a pH-sensitive measure, with higher values associated with greater neuropathological burden. The authors investigated the relationship between T1rho imaging and AD-associated pathologies as determined by available diagnostic imaging techniques.

Methods:

Twenty-seven participants (men, N=13, women, N=14; ages 55–90) across the cognitive spectrum (healthy control subjects [HCs] with normal cognition, N=17; participants with mild cognitive impairment [MCI], N=7; participants with mild AD, N=3) underwent neuropsychological testing, MRI (T1-weighted and T1rho [spin-lattice relaxation time in the rotating frame]), and positron emission tomography imaging ([11C]Pittsburg compound B for amyloid burden [N=26] and [18F]fluorodeoxyglucose for cerebral glucose metabolism [N=12]). The relationships between global T1rho values and neuropsychological, demographic, and imaging measures were explored.

Results:

Global mean and median T1rho were positively associated with age. After controlling for age, higher global T1rho was associated with poorer cognitive function, poorer memory function (immediate and delayed memory scores), higher amyloid burden, and more abnormal cerebral glucose metabolism. Regional T1rho values, when controlling for age, significantly differed between HCs and participants with MCI or AD in select frontal, cingulate, and parietal regions.

Conclusions:

Higher T1rho values were associated with greater cognitive impairment and pathological burden. T1rho, a biomarker that varies according to a feature common to each cascade rather than one that is unique to a particular pathology, has the potential to serve as a metric of neuropathology, theoretically providing a measure for assessing pathological status and for monitoring the neurodegeneration trajectory.

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Information

Published In

Go to The Journal of Neuropsychiatry and Clinical Neurosciences
Go to The Journal of Neuropsychiatry and Clinical Neurosciences
The Journal of Neuropsychiatry and Clinical Neurosciences
Pages: 352 - 361
PubMed: 32283991

History

Received: 16 October 2019
Revision received: 26 December 2019
Accepted: 18 February 2020
Published online: 14 April 2020
Published in print: Fall 2020

Keywords

  1. Alzheimer’s Disease
  2. Parkinson’s Disease
  3. Mild Cognitive Impairment
  4. Aging of the Brain

Authors

Affiliations

Laura L. Boles Ponto, Ph.D. [email protected]
Department of Radiology (Boles Ponto, Magnotta, Menda, Harlynn), Department of Psychiatry (Magnotta, Moser, Wemmie, Schultz), Carver College of Medicine, and Department of Biostatistics, College of Public Health (Oleson, DeVries), University of Iowa, Iowa City.
Vincent A. Magnotta, Ph.D.
Department of Radiology (Boles Ponto, Magnotta, Menda, Harlynn), Department of Psychiatry (Magnotta, Moser, Wemmie, Schultz), Carver College of Medicine, and Department of Biostatistics, College of Public Health (Oleson, DeVries), University of Iowa, Iowa City.
Yusuf Menda, M.D.
Department of Radiology (Boles Ponto, Magnotta, Menda, Harlynn), Department of Psychiatry (Magnotta, Moser, Wemmie, Schultz), Carver College of Medicine, and Department of Biostatistics, College of Public Health (Oleson, DeVries), University of Iowa, Iowa City.
David J. Moser, Ph.D.
Department of Radiology (Boles Ponto, Magnotta, Menda, Harlynn), Department of Psychiatry (Magnotta, Moser, Wemmie, Schultz), Carver College of Medicine, and Department of Biostatistics, College of Public Health (Oleson, DeVries), University of Iowa, Iowa City.
Jacob J. Oleson, Ph.D.
Department of Radiology (Boles Ponto, Magnotta, Menda, Harlynn), Department of Psychiatry (Magnotta, Moser, Wemmie, Schultz), Carver College of Medicine, and Department of Biostatistics, College of Public Health (Oleson, DeVries), University of Iowa, Iowa City.
Emily L. Harlynn, B.S.
Department of Radiology (Boles Ponto, Magnotta, Menda, Harlynn), Department of Psychiatry (Magnotta, Moser, Wemmie, Schultz), Carver College of Medicine, and Department of Biostatistics, College of Public Health (Oleson, DeVries), University of Iowa, Iowa City.
Sean D. DeVries, M.S.
Department of Radiology (Boles Ponto, Magnotta, Menda, Harlynn), Department of Psychiatry (Magnotta, Moser, Wemmie, Schultz), Carver College of Medicine, and Department of Biostatistics, College of Public Health (Oleson, DeVries), University of Iowa, Iowa City.
John A. Wemmie, M.D., Ph.D.
Department of Radiology (Boles Ponto, Magnotta, Menda, Harlynn), Department of Psychiatry (Magnotta, Moser, Wemmie, Schultz), Carver College of Medicine, and Department of Biostatistics, College of Public Health (Oleson, DeVries), University of Iowa, Iowa City.
Susan K. Schultz, M.D.
Department of Radiology (Boles Ponto, Magnotta, Menda, Harlynn), Department of Psychiatry (Magnotta, Moser, Wemmie, Schultz), Carver College of Medicine, and Department of Biostatistics, College of Public Health (Oleson, DeVries), University of Iowa, Iowa City.

Notes

Presented in part as an abstract at the annual meetings of the Society of Nuclear Medicine and Molecular Imaging, St. Louis, June 7–11, 2014, and San Diego, June 11–15, 2016.
Send correspondence to Dr. Ponto ([email protected]).

Competing Interests

The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Funding Information

Supported in part by the Biological Sciences Funding Program of the Office of the Vice President for Research, University of Iowa, and NIH (grant R03AG047306; co–principal investigators, Drs. Boles Ponto and Schultz). The development of the T1rho imaging sequence was supported in part by NIH (grants R01EB022019 and R01MH111578). MRI was performed on equipment supported by a high-end instrumentation (NIH grant S10OD025025-01).

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