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Cortical hypermetabolism in MCI subjects: a compensatory mechanism?

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Alzheimer’s disease (AD) is associated with amyloid accumulation that takes place decades before symptoms appear. Cognitive impairment in AD is associated with reduced glucose metabolism. However, neuronal plasticity/compensatory mechanisms might come into play before the onset of dementia. The aim of this study was to determine whether there is evidence of cortical hypermetabolism as a compensatory mechanism before amyloid deposition takes place in subjects with amnestic mild cognitive impairment (aMCI).

Methods

Nine AD subjects and ten aMCI subjects had both [11C]PIB and [18F]FDG PET scans with arterial input in order to quantify the amyloid deposition and glucose metabolism in vivo in comparison with healthy control subjects who underwent either [11C]PIB or [18F]FDG PET scans. The [11C]PIB PET scans were quantified using [11C]PIB target region to cerebellum uptake ratio images created by integrating the activity collected from 60 to 90 min, and regional cerebral glucose metabolism was quantified using spectral analysis.

Results

In MCI subjects, cortical hypermetabolism was observed in four amyloid-negative subjects and one amyloid-positive subject, while hypometabolism was seen in five other MCI subjects with high amyloid load. Subjects with hypermetabolism and low amyloid did not convert to AD during clinical follow-up for 18 months in contrast to four amyloid-positive hypometabolic subjects who did convert to AD.

Conclusion

This preliminary study suggests that compensatory hypermetabolism can occur in aMCI subjects, particularly in those who are amyloid-negative. The increase in metabolic rate in different cortical regions with predominance in the occipital cortex may be a compensatory response to the neuronal damage occurring early in the disease process. It may also reflect recruitment of relatively minimally affected cortical regions to compensate for reduced function in the temporoparietal cortical association areas.

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Acknowledgments

The authors thank Hammersmith Imanet, GE Healthcare, for the provision of radiotracers, and scanning and blood analysis equipment. P. Edison was funded by the Medical Research Council and now by the Higher Education Funding Council for England (HEFCE). The PET scans and MRI scans were funded by the Medical Research Council and Alzheimer’s Research UK.

This research was supported by the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

Conflicts of interest

This study was funded by Medical Research Council, UK. Dr. Edison has received funding from Medical Research Council, UK, as his fellowship/salary. Prof. Brooks is also the chief medical officer for GE Healthcare. Ms. Fan and Mr. Ashraf have nothing to disclose.

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  1. Neurology Imaging Unit, Division of Brain Sciences, Imperial College London, Block B Hammersmith Campus, Du Cane Road, London, W12 0NN, UK

    A. Ashraf, Z. Fan, D. J. Brooks & P. Edison

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  1. A. Ashraf
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Ashraf, A., Fan, Z., Brooks, D.J. et al. Cortical hypermetabolism in MCI subjects: a compensatory mechanism?. Eur J Nucl Med Mol Imaging 42, 447–458 (2015). https://doi.org/10.1007/s00259-014-2919-z

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