title: Fluorodeoxyglucose metabolism associated with tau-amyloid interaction predicts memory decline.
abstract: OBJECTIVE
  The aim of this article was to evaluate in normal older adults and preclinical Alzheimer's disease (AD) the impact of amyloid and regional tauopathy on cerebral glucose metabolism and subsequent memory decline.
  
  
  METHODS
  We acquired positron emission tomography using F18 flortaucipir (tau), C11 Pittsburgh compound B (amyloid), and F18 fluorodeoxyglucose (FDG) in 90 clinically normal elderly of the Harvard Aging Brain Study.
  
  
  RESULTS
  Posterior cingulate metabolism decreased when both amyloid and neocortical tau were high and predicted subsequent memory decline in a larger sample of normal elderly. In contrast, frontal hypometabolism related to the common age-related entorhinal tauopathy, but this dysfunction was independent of amyloid, and did not predict significant memory decline. Neocortical tauopathy was positively associated with metabolism in individuals with subthreshold amyloid, suggesting that glucose metabolism increases before decreasing in the course of preclinical AD.
  
  
  CONCLUSIONS
  Our study identified a synergistic effect of amyloid and tau deposits and demonstrated, for the first time, in normal elderly its link to AD-like hypometabolism and to AD-like memory decline. The amyloid effect was observed with tau in neocortex, but not with tau in entorhinal cortex, which is the common site of age-related tauopathy. Entorhinal tau was associated with frontal hypometabolism, but this dysfunction was not associated with memory loss. Ann Neurol 2017;81:583-596.
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, and the Martinos Center for Biomedical Imaging, Charlestown, MA.|Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Hanseeuw
authors.affiliation: Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Betensky
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, and the Martinos Center for Biomedical Imaging, Charlestown, MA.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Schultz
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, and the Martinos Center for Biomedical Imaging, Charlestown, MA.|Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Kathryn V
authors.initials: KV
authors.lastname: Papp
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, and the Martinos Center for Biomedical Imaging, Charlestown, MA.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Mormino
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sepulcre
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: John S
authors.initials: JS
authors.lastname: Bark
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Cosio
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, and the Martinos Center for Biomedical Imaging, Charlestown, MA.
authors.forename: Molly
authors.initials: M
authors.lastname: LaPoint
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, and the Martinos Center for Biomedical Imaging, Charlestown, MA.
authors.forename: Jasmeer P
authors.initials: JP
authors.lastname: Chhatwal
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, and the Martinos Center for Biomedical Imaging, Charlestown, MA.|Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Dorene M
authors.initials: DM
authors.lastname: Rentz
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, and the Martinos Center for Biomedical Imaging, Charlestown, MA.|Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, and the Martinos Center for Biomedical Imaging, Charlestown, MA.|Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.|Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Johnson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000502:physiology; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D010168:Palmitates; D049268:Positron-Emission Tomography; D011379:Prognosis; D019275:Radiopharmaceuticals; D013844:Thiazoles; D013871:Thiones; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C515150:16-fluoro-4-thiapalmitic acid; C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D010168:Palmitates; D019275:Radiopharmaceuticals; D013844:Thiazoles; D013871:Thiones; D016875:tau Proteins; D019788:Fluorodeoxyglucose F18