Abstract
Purpose
It has been suggested that neuronal energy metabolism may be involved in Alzheimer’s disease (AD). In this view, the finding of increased cerebrospinal fluid (CSF) lactate levels in AD patients has been considered the result of energetic metabolism dysfunction. Here, we investigated the relationship between neuronal energy metabolism, as measured via CSF lactate levels, and cerebral glucose metabolism, as stated at the 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography ([18F]FDG PET) in AD patients.
Methods
AD patients underwent lumbar puncture to measure CSF lactate levels and [18F]FDG PET to assess brain glucose metabolism. CSF and PET data were compared to controls. Since patients were studied at rest, we specifically investigated brain areas active in rest-condition owing to the Default Mode Network (DMN). We correlated the CSF lactate concentrations with the [18F]FDG PET data in brain areas owing to the DMN, using sex, age, disease duration, Mini Mental State Examination, and CSF levels of tau proteins and beta-amyloid as covariates.
Results
AD patients (n = 32) showed a significant increase of CSF lactate levels compared to Control 1 group (n = 28). They also showed brain glucose hypometabolism in the DMN areas compared to Control 2 group (n = 30). Within the AD group we found the significant correlation between increased CSF lactate levels and glucose hypometabolism in Broadman areas (BA) owing to left medial prefrontal cortex (BA10, mPFC), left orbitofrontal cortex (BA11, OFC), and left parahippocampal gyrus (BA 35, PHG).
Conclusion
We found high CSF levels of lactate and glucose hypometabolism within the DMN in AD patients. Moreover, we found a relationship linking the increased CSF lactate and the reduced glucose consumption in the left mPFC, OFC and PHG, owing to the anterior hub of DMN. These findings could suggest that neural glucose hypometabolism may affect the DMN efficiency in AD, also proposing the possible role of damaged brain energetic machine in impairing DMN.
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Authors' contributions
Claudio Liguori: study concept, acquisition of data, data analysis and interpretation, statistical analysis, drafting the manuscript.
Agostino Chiaravalloti: PET data acquisition and analysis, statistical analysis, drafting the manuscript.
Giuseppe Sancesario: study supervision, critical revision of the manuscript for important intellectual content.
Alessandro Stefani: critical revision of the manuscript for important intellectual content
Giulia Maria Sancesario: data analysis
Nicola Biagio Mercuri: study supervision
Orazio Schillaci: critical revision of the manuscript for important intellectual content
Mariangela Pierantozzi: study concept and supervision, data analysis and interpretation, statistical analysis, drafting the manuscript.
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Claudio Liguori, Agostino Chiaravalloti, Giuseppe Sancesario, Alessandro Stefani, Giulia Maria Sancesario, Orazio Schillaci, Nicola Biagio Mercuri, Mariangela Pierantozzi report no financial discosures/fundings or conflict of interest.
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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.
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Informed consent was obtained from all individual participants included in the study.
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Claudio Liguori and Agostino Chiaravalloti contributed equally to this work.
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Liguori, C., Chiaravalloti, A., Sancesario, G. et al. Cerebrospinal fluid lactate levels and brain [18F]FDG PET hypometabolism within the default mode network in Alzheimer’s disease. Eur J Nucl Med Mol Imaging 43, 2040–2049 (2016). https://doi.org/10.1007/s00259-016-3417-2
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DOI: https://doi.org/10.1007/s00259-016-3417-2