title: Association of hypometabolism and amyloid levels in aging, normal subjects.
abstract: OBJECTIVE
  We evaluated the relationship of amyloid, seen on Pittsburgh compound B (PiB)-PET, and metabolism, seen on [(18)F]-fluorodeoxyglucose (FDG)-PET, in normal subjects to better understand pathogenesis and biomarker selection in presymptomatic subjects.
  
  
  METHODS
  Normal participants (aged 70-95 years; 600 with PiB-PET, FDG-PET, and MRI) were included. We performed a cross-sectional evaluation and subcategorized participants into amyloid-negative (<1.4), high-normal (1.4-1.5), positive (1.5-2.0), and markedly positive (>2.0) PiB standardized uptake value ratio groups representing different levels of amyloid brain load. Associations with metabolism were assessed in each group. Relationships with APOE ε4 carriage were evaluated.
  
  
  RESULTS
  Hypometabolism in "Alzheimer disease (AD)-signature" regions was strongly associated with PiB load. Hypometabolism was greater with more positive PiB levels. Additional, more-diffuse cortical hypometabolism was also found to be associated with PiB, although less so. No hypermetabolism was seen in any subset. No significant incremental hypometabolism was seen in APOE-positive vs -negative subjects.
  
  
  CONCLUSIONS
  Hypometabolism in PiB-positive, cognitively normal subjects in a population-based cohort occurs in AD-signature cortical regions and to a lesser extent in other cortical regions. It is more pronounced with higher amyloid load and supports a dose-dependent association. The effect of APOE ε4 carriage in this group of subjects does not appear to modify their hypometabolic "AD-like" neurodegeneration. Consideration of hypometabolism associated with amyloid load may aid trials of AD drug therapy.
authors.affiliation: From the Departments of Radiology (V.J.L., M.L.S., P.V., L.J., K.K., C.R.J.), Health Sciences Research (S.D.W.), and Neurology (B.B., D.K., R.C.P.), Mayo Clinic, Rochester, MN. vlowe@mayo.edu.
authors.forename: Val J
authors.initials: VJ
authors.lastname: Lowe
authors.affiliation: From the Departments of Radiology (V.J.L., M.L.S., P.V., L.J., K.K., C.R.J.), Health Sciences Research (S.D.W.), and Neurology (B.B., D.K., R.C.P.), Mayo Clinic, Rochester, MN.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Weigand
authors.affiliation: From the Departments of Radiology (V.J.L., M.L.S., P.V., L.J., K.K., C.R.J.), Health Sciences Research (S.D.W.), and Neurology (B.B., D.K., R.C.P.), Mayo Clinic, Rochester, MN.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Senjem
authors.affiliation: From the Departments of Radiology (V.J.L., M.L.S., P.V., L.J., K.K., C.R.J.), Health Sciences Research (S.D.W.), and Neurology (B.B., D.K., R.C.P.), Mayo Clinic, Rochester, MN.
authors.forename: Prashanthi
authors.initials: P
authors.lastname: Vemuri
authors.affiliation: From the Departments of Radiology (V.J.L., M.L.S., P.V., L.J., K.K., C.R.J.), Health Sciences Research (S.D.W.), and Neurology (B.B., D.K., R.C.P.), Mayo Clinic, Rochester, MN.
authors.forename: Lennon
authors.initials: L
authors.lastname: Jordan
authors.affiliation: From the Departments of Radiology (V.J.L., M.L.S., P.V., L.J., K.K., C.R.J.), Health Sciences Research (S.D.W.), and Neurology (B.B., D.K., R.C.P.), Mayo Clinic, Rochester, MN.
authors.forename: Kejal
authors.initials: K
authors.lastname: Kantarci
authors.affiliation: From the Departments of Radiology (V.J.L., M.L.S., P.V., L.J., K.K., C.R.J.), Health Sciences Research (S.D.W.), and Neurology (B.B., D.K., R.C.P.), Mayo Clinic, Rochester, MN.
authors.forename: Bradley
authors.initials: B
authors.lastname: Boeve
authors.affiliation: From the Departments of Radiology (V.J.L., M.L.S., P.V., L.J., K.K., C.R.J.), Health Sciences Research (S.D.W.), and Neurology (B.B., D.K., R.C.P.), Mayo Clinic, Rochester, MN.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: From the Departments of Radiology (V.J.L., M.L.S., P.V., L.J., K.K., C.R.J.), Health Sciences Research (S.D.W.), and Neurology (B.B., D.K., R.C.P.), Mayo Clinic, Rochester, MN.
authors.forename: David
authors.initials: D
authors.lastname: Knopman
authors.affiliation: From the Departments of Radiology (V.J.L., M.L.S., P.V., L.J., K.K., C.R.J.), Health Sciences Research (S.D.W.), and Neurology (B.B., D.K., R.C.P.), Mayo Clinic, Rochester, MN.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism*; D000814:Aniline Compounds; D053327:Apolipoprotein E4 / Q000235:genetics; D002540:Cerebral Cortex / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D064847:Multimodal Imaging / Q000295:instrumentation / Q000379:methods; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D019275:Radiopharmaceuticals; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18