MRI and MRS predictors of mild cognitive impairment in a population-based sample
Abstract
Objective:
To investigate MRI and proton magnetic resonance spectroscopy (MRS) predictors of mild cognitive impairment (MCI) in cognitively normal older adults.
Methods:
Subjects were cognitively normal older adults (n = 1,156) who participated in the population-based Mayo Clinic Study of Aging MRI/MRS study from August 2005 to December 2010 and had at least one annual clinical follow-up. Single-voxel MRS was performed from the posterior cingulate gyri, and hippocampal volumes and white matter hyperintensity volumes were quantified using automated methods. Brain infarcts were assessed on MRI. Cox proportional hazards regression, with age as the time scale, was used to assess the effect of MRI and MRS markers on the risk of progression from cognitively normal to MCI. Linear mixed-effects models were used to assess the effect of MRI and MRS markers on cognitive decline.
Results:
After a median follow-up of 2.8 years, 214 participants had progressed to MCI or dementia (estimated incidence rate = 6.1% per year; 95% confidence interval = 5.3%–7.0%). In univariable modeling, hippocampal volume, white matter hyperintensity volume, and N-acetylaspartate/myo-inositol were significant predictors of MCI in cognitively normal older adults. In multivariable modeling, only decreased hippocampal volume and N-acetylaspartate/myo-inositol were independent predictors of MCI. These MRI/MRS predictors of MCI as well as infarcts were associated with cognitive decline (p < 0.05).
Conclusion:
Quantitative MRI and MRS markers predict progression to MCI and cognitive decline in cognitively normal older adults. MRS may contribute to the assessment of preclinical dementia pathologies by capturing neurodegenerative changes that are not detected by hippocampal volumetry.
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Information & Authors
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Copyright
© 2013 American Academy of Neurology.
Publication History
Received: August 20, 2012
Accepted: March 25, 2013
Published online: June 12, 2013
Published in print: July 9, 2013
Disclosure
K. Kantarci serves on the data safety monitoring board for Pfizer Inc., Takeda Global Research & Development Center, Inc.; and is funded by the NIH. S. Weigand, S. Przybelski, and G. Preboski report no disclosures. V.S. Pankratz is funded by the NIH. P. Vemuri is funded by the NIH and Alzheimer’s Association New Investigator Award. M. Senjem, M. Murphy, M. Machulda, and J. Gunter report no disclosures. R. Ivnik receives research support from the NIH. R. Roberts receives research support from the NIH, Abbott Laboratories, and the Driskill Foundation. B. Boeve has served as an investigator for a clinical trial sponsored by Cephalon, Inc. He has received honoraria from the American Academy of Neurology. He receives research support from the National Institute on Aging and the Alzheimer’s Association. W. Rocca receives research support from the NIH and the DHHS. D. Knopman serves as Deputy Editor for Neurology®; serves on a data safety monitoring board for Lilly Pharmaceuticals; is an investigator in a clinical trial sponsored by Janssen Pharmaceuticals; and receives research support from the NIH. R. Petersen serves on scientific advisory boards for Elan Pharmaceuticals, Wyeth Pharmaceuticals, and GE Healthcare; and receives research support from the NIH. C. Jack serves as a consultant for Janssen, Bristol-Myers Squibb, General Electric, and Johnson & Johnson, and is involved in clinical trials sponsored by Allon and Baxter, Inc. He receives research funding from the NIH and the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Foundation. Go to Neurology.org for full disclosures.
Study Funding
This work was supported by the NIH (U01 AG06786, R01 AG11378, R01 AG040042, C06 RR018898) and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program.
Authors
Author Contributions
Dr. Kantarci: study concept and design, acquisition of data, analysis and interpretation of the data, drafting the manuscript. Mr. Weigand: study concept and design, analysis or interpretation of the data, critical revision of the manuscript for important intellectual content. Mr. Przybelski: analysis or interpretation of the data, critical revision of the manuscript for important intellectual content. Mr. Preboske: acquisition of data, critical revision of the manuscript for important intellectual content. Dr. Pankratz: study concept and design, analysis or interpretation of the data, critical revision of the manuscript for important intellectual content. Dr. Vemuri, Mr. Senjem, Dr. Murphy, Dr. Gunter, Dr. Machulda, Dr. Ivnik, Dr. Roberts, Dr. Boeve, Dr. Rocca, Dr. Knopman, and Dr. Petersen: acquisition of data, critical revision of the manuscript for important intellectual content. Dr. Jack: study concept and design, acquisition of data, critical revision of the manuscript for important intellectual content.
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