title: Lower brain 18F-fluorodeoxyglucose uptake but normal 11C-acetoacetate metabolism in mild Alzheimer's disease dementia.
abstract: BACKGROUND
  The cerebral metabolic rate of glucose (CMRg) is lower in specific brain regions in Alzheimer's disease (AD). The ketones, acetoacetate and β-hydroxybutyrate, are the brain's main alternative energy substrates to glucose.
  
  
  OBJECTIVE
  To gain insight into brain fuel metabolism in mild AD dementia by determining whether the regional CMR and the rate constant of acetoacetate (CMRa and Ka, respectively) reflect the same metabolic deficit reported for cerebral glucose uptake (CMRg and Kg).
  
  
  METHODS
  Mild AD dementia (Mild AD; n = 10, age 76 y) patients were compared with gender- and age-matched cognitively normal older adults (Controls; n = 29, age 75 y) using a PET/MRI protocol and analyzed with both ROI- and voxel-based methods.
  
  
  RESULTS
  ROI-based analysis showed 13% lower global CMRg in the gray matter of mild AD dementia versus Controls (34.2 ± 5.0 versus 38.3 ± 4.7 μmol/100 g/min, respectively; p = 0.015), with CMRg and Kg in the parietal cortex, posterior cingulate, and thalamus being the most affected (p ≤ 0.022). Neither global nor regional CMRa or Ka differed between the two groups (all p ≥ 0.188). Voxel-based analysis showed a similar metabolic pattern to ROI-based analysis with seven clusters of significantly lower CMRg in the mild AD dementia group (uncorrected p ≤ 0.005) but with no difference in CMRa.
  
  
  CONCLUSIONS
  Regional brain energy substrate hypometabolism in mild AD dementia may be specific to impaired glucose uptake and/or utilization. This suggests a potential avenue for compensating brain energy deficit in AD dementia with ketones.
authors.affiliation: Research Center on Aging, Health and Social Sciences Center, Geriatrics Institute, Sherbrooke, QC, Canada Department Physiology and Biophysics, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Christian-Alexandre
authors.initials: CA
authors.lastname: Castellano
authors.affiliation: Research Center on Aging, Health and Social Sciences Center, Geriatrics Institute, Sherbrooke, QC, Canada Department Physiology and Biophysics, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: Nugent
authors.affiliation: Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Nancy
authors.initials: N
authors.lastname: Paquet
authors.affiliation: Sherbrooke Molecular Imaging Center, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Tremblay
authors.affiliation: Research Center on Aging, Health and Social Sciences Center, Geriatrics Institute, Sherbrooke, QC, Canada Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Bocti
authors.affiliation: Research Center on Aging, Health and Social Sciences Center, Geriatrics Institute, Sherbrooke, QC, Canada Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Guy
authors.initials: G
authors.lastname: Lacombe
authors.affiliation: Research Center on Aging, Health and Social Sciences Center, Geriatrics Institute, Sherbrooke, QC, Canada.
authors.forename: Hélène
authors.initials: H
authors.lastname: Imbeault
authors.affiliation: Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, QC, Canada Sherbrooke Molecular Imaging Center, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Éric
authors.initials: É
authors.lastname: Turcotte
authors.affiliation: Research Center on Aging, Health and Social Sciences Center, Geriatrics Institute, Sherbrooke, QC, Canada Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Tamas
authors.initials: T
authors.lastname: Fulop
authors.affiliation: Research Center on Aging, Health and Social Sciences Center, Geriatrics Institute, Sherbrooke, QC, Canada Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Cunnane
mesh_terms: D000090:Acetoacetates / Q000378:metabolism; D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D007659:Ketones / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012815:Signal Processing, Computer-Assisted
chemical_list: D000090:Acetoacetates; D002250:Carbon Radioisotopes; D007659:Ketones; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C016635:acetoacetic acid; D005947:Glucose
keywords: Acetoacetate; Alzheimer's disease; cerebral metabolic rate; energy metabolism; glucose; ketones; β-hydroxybutyrate