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1H MRS spectroscopy in preclinical autosomal dominant Alzheimer disease

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Abstract

1H magnetic resonance spectroscopy (MRS) can reveal changes in brain biochemistry in vivo in humans and has been applied to late onset Alzheimer disease (AD). Carriers of mutations for autosomal dominant Alzheimer disease (ADAD) may show changes in levels of metabolites prior to the onset of clinical symptoms. Proton MR spectra were acquired at 1.5 T for 16 cognitively asymptomatic or mildly symptomatic mutation carriers (CDR < 1) and 11 non-carriers as part of a comprehensive cross-sectional study of preclinical ADAD. Levels of N-acetyl-aspartate+N-acetyl-aspartyl-glutamate (NAA), glutamate/glutamine (Glx), creatine/phosphocreate (Cr), choline (Cho), and myo-inositol (mI) in the left and right anterior cingulate and midline posterior cingulate and precuneus were compared between mutation carriers (MCs) and non-carriers (NCs) using multivariate analysis of variance with age as a covariate. Among MCs, correlations between metabolite levels and time until expected age of dementia diagnosis were calculated. MCs had significantly lower levels of NAA and Glx in the left pregenual anterior cingulate cortex, and lower levels of NAA and higher levels of mI and Cho in the precuneus compared to NCs. Increased levels of mI were seen in these regions in association with increased proximity to expected age of dementia onset. MRS shows effects of ADAD similar to those seen in late onset AD even during the preclinical period including lower levels of NAA and higher levels of mI. These indices of neuronal and glial dysfunction might serve as surrogate outcome measures in prevention studies of putative disease-modifying agents.

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Funding

This research was supported by the National Institutes of Health under award numbers P50 AG0005142, K08 AG022228, P50 AG016570.

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Authors and Affiliations

  1. Alzheimer Disease Research Center, Keck School of Medicine, Univeristy of Southern California, Center for Health Professions, 1540 Alcazar Street, Los Angeles, CA, 90033, USA

    Elizabeth Joe & John M. Ringman

  2. Easton Center for Alzheimer’s Disease Research, University of California, Los Angeles, 710 Westwood Plaza, Room C-224, Los Angeles, CA, 90095, USA

    Luis D. Medina & John M. Ringman

  3. Department of Neurosurgery, University of Colorado School of Medicine, 12631 E. 17th Ave., C307, Aurora, CO, 80045, USA

    Luis D. Medina

  4. Division of Child & Adolescent Psychiatry, Semel Institute For Neuroscience, University of California, Los Angeles, 760 Westwood Plaza, 58-227, Los Angeles, CA, 90095, USA

    Joseph O’Neill

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  1. Elizabeth Joe
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Correspondence to Elizabeth Joe.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Joe, E., Medina, L.D., Ringman, J.M. et al. 1H MRS spectroscopy in preclinical autosomal dominant Alzheimer disease. Brain Imaging and Behavior 13, 925–932 (2019). https://doi.org/10.1007/s11682-018-9913-1

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