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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.
GLOSSARY
- AD=
- Alzheimer disease;
- Cr=
- creatine;
- DSM-III-R=
- Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised;
- FDG=
- 18F-fluorodeoxyglucose;
- FLAIR=
- fluid-attenuated inversion recovery;
- 1H-MRS=
- proton magnetic resonance spectroscopy;
- HR=
- hazard ratio;
- IQR=
- interquartile range;
- MCI=
- mild cognitive impairment;
- MCSA=
- Mayo Clinic Study of Aging;
- mI=
- myo-inositol;
- MRS=
- magnetic resonance spectroscopy;
- NAA=
- N-acetylaspartate;
- TIV=
- total intracranial volume;
- WM=
- white matter;
- WMH=
- white matter hyperintensity
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received August 20, 2012.
- Accepted in final form March 25, 2013.
- © 2013 American Academy of Neurology
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