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18F–FDG PET diagnostic and prognostic patterns do not overlap in Alzheimer’s disease (AD) patients at the mild cognitive impairment (MCI) stage

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

Abstract

Purpose

We aimed to identify the cortical regions where hypometabolism can predict the speed of conversion to dementia in mild cognitive impairment due to Alzheimer’s disease (MCI-AD).

Methods

We selected from the clinical database of our tertiary center memory clinic, eighty-two consecutive MCI-AD that underwent 18F–fluorodeoxyglucose (FDG) PET at baseline during the first diagnostic work-up and were followed up at least until their clinical conversion to AD dementia. The whole group of MCI-AD was compared in SPM8 with a group of age-matched healthy controls (CTR) to verify the presence of AD diagnostic-pattern; then the correlation between conversion time and brain metabolism was assessed to identify the prognostic-pattern. Significance threshold was set at p < 0.05 False-Discovery-Rate (FDR) corrected at peak and at cluster level. Each MCI-AD was then compared with CTR by means of a SPM single-subject analysis and grouped according to presence of AD diagnostic-pattern and prognostic-pattern. Kaplan-Meier-analysis was used to evaluate if diagnostic- and/or prognostic-patterns can predict speed of conversion to dementia.

Results

Diagnostic-pattern corresponded to typical posterior hypometabolism (BA 7, 18, 19, 30, 31 and 40) and did not correlate with time to conversion, which was instead correlated with metabolic levels in right middle and inferior temporal gyri as well as in the fusiform gyrus (prognostic-pattern, BA 20, 21 and 38). At Kaplan-Meier analysis, patients with hypometabolism in the prognostic pattern converted to AD-dementia significantly earlier than patients not showing significant hypometabolism in the right middle and inferior temporal cortex (9 versus 19 months; Log rank p < 0.02, Breslow test: p < 0.003, Tarone-Ware test: p < 0.007).

Conclusion

The present findings support the role of FDG PET as a robust progression biomarker even in a naturalist population of MCI-AD. However, not the AD-typical diagnostic-pattern in posterior regions but the middle and inferior temporal metabolism captures speed of conversion to dementia in MCI-AD since baseline. The highlighted prognostic pattern is a further, independent source of heterogeneity in MCI-AD and affects a primary-endpoint on interventional clinical trials (time of conversion to dementia).

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Author information

Authors and Affiliations

  1. Nuclear Medicine Unit, IRCCS AOU San Martino, IST and Department of Health Sciences, University of Genoa, Largo R. Benzi 10, 16132, Genoa, Italy

    Silvia Morbelli, Matteo Bauckneht, Ambra Buschiazzo, Alberto Nieri & Gianmario Sambuceti

  2. Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa and IRCCS AOU San Martino-IST, Genoa, Italy

    Dario Arnaldi, Agnese Picco, Matteo Pardini, Andrea Brugnolo, Nicola Girtler & Flavio Nobili

  3. Institute of Cognitive Sciences and Technologies, CNR, Rome, Italy

    Marco Pagani

  4. Department of Nuclear Medicine, Karolinska Hospital, Stockholm, Sweden

    Marco Pagani

  5. Istituto Nazionale di Fisica Nucleare, Sezione di Genova, Genoa, Italy

    Andrea Chincarini

  6. Institute of Bioimaging and Molecular Physiology, National Research Council, Genoa, Italy

    Fabrizio De Carli

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  1. Silvia Morbelli
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Correspondence to Silvia Morbelli.

Ethics declarations

All the performed procedures 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.

Funding

No financial support has been provided for this study. The authors do not declare conflict of interest. Silvia Morbelli acted as consultant for Eli Lilly in 2014 and for Avid Radiopharmaceuticals in 2016 and Flavio Nobili acted as consultant for Eli Lilly in 2014.

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Morbelli, S., Bauckneht, M., Arnaldi, D. et al. 18F–FDG PET diagnostic and prognostic patterns do not overlap in Alzheimer’s disease (AD) patients at the mild cognitive impairment (MCI) stage. Eur J Nucl Med Mol Imaging 44, 2073–2083 (2017). https://doi.org/10.1007/s00259-017-3790-5

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