title: Cerebrospinal fluid lactate levels and brain [18F]FDG PET hypometabolism within the default mode network in Alzheimer's disease.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neurophysiopathology Unit, Department of Systems Medicine, University of Rome "Tor Vergata", Viale Oxford 81, 00133, Rome, Italy. dott.claudioliguori@yahoo.it.|Neurology Unit, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy. dott.claudioliguori@yahoo.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Liguori
authors.affiliation: Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Rome, Italy.|IRCSS Neuromed, Pozzilli, Italy.
authors.forename: Agostino
authors.initials: A
authors.lastname: Chiaravalloti
authors.affiliation: Neurology Unit, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.|IRCCS Fondazione Santa Lucia, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sancesario
authors.affiliation: Neurology Unit, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.|IRCCS Fondazione Santa Lucia, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Stefani
authors.affiliation: IRCCS Fondazione Santa Lucia, Rome, Italy.
authors.forename: Giulia Maria
authors.initials: GM
authors.lastname: Sancesario
authors.affiliation: Neurophysiopathology Unit, Department of Systems Medicine, University of Rome "Tor Vergata", Viale Oxford 81, 00133, Rome, Italy.|Neurology Unit, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.|IRCCS Fondazione Santa Lucia, Rome, Italy.
authors.forename: Nicola Biagio
authors.initials: NB
authors.lastname: Mercuri
authors.affiliation: Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Rome, Italy.|IRCSS Neuromed, Pozzilli, Italy.
authors.forename: Orazio
authors.initials: O
authors.lastname: Schillaci
authors.affiliation: Neurology Unit, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Pierantozzi
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001928:Brain Diseases, Metabolic / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000134:cerebrospinal fluid*; D008657:Metabolic Clearance Rate; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D019344:Lactic Acid; D005947:Glucose
keywords: Alzheimer's disease; CSF lactate; Default mode network; [18F]FDG PET