title: Age and neurodegeneration imaging biomarkers in persons with Alzheimer disease dementia.
abstract: OBJECTIVE
  To examine neurodegenerative imaging biomarkers in Alzheimer disease (AD) dementia from middle to old age.
  
  
  METHODS
  Persons with AD dementia and elevated brain β-amyloid with Pittsburgh compound B (PiB)-PET imaging underwent [(18)F]-fluorodeoxyglucose (FDG)-PET and structural MRI. We evaluated 3 AD-related neurodegeneration biomarkers: hippocampal volume adjusted for total intracranial volume (HVa), FDG standardized uptake value ratio (SUVR) in regions of interest linked to AD, and cortical thickness in AD-related regions of interest. We examined associations of each biomarker with age and evaluated age effects on cutpoints defined by the 90th percentile in AD dementia. We assembled an age-, sex-, and intracranial volume-matched group of 194 similarly imaged clinically normal (CN) persons.
  
  
  RESULTS
  The 97 participants with AD dementia (aged 49-93 years) had PiB SUVR ≥1.8. A nonlinear (inverted-U) relationship between FDG SUVR and age was seen in the AD group but an inverse linear relationship with age was seen in the CN group. Cortical thickness had an inverse linear relationship with age in AD but a nonlinear (flat, then inverse linear) relationship in the CN group. HVa showed an inverse linear relationship with age in both AD and CN groups. Age effects on 90th percentile cutpoints were small for FDG SUVR and cortical thickness, but larger for HVa.
  
  
  CONCLUSIONS
  In persons with AD dementia with elevated PiB SUVR, values of each neurodegeneration biomarker were associated with age. Cortical thickness had the smallest differences in 90th percentile cutpoints from middle to old age, and HVa the largest differences.
authors.affiliation: From the Departments of Neurology (D.S.K., P.V., M.M. Mielke, R.O.R., B.F.B., D.T.J., R.C.P.) and Radiology (C.R.J., V.J.L., K.K., J.L.G., M.L.S., D.T.J.), Mayo Clinic Alzheimer's Disease Research Center (D.S.K., C.R.J., B.F.B., D.T.J., R.C.P.), Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (H.J.W., S.D.W.), Division of Epidemiology, Department of Health Sciences Research (M.M. Mielke, R.O.R., R.C.P.), and Department of Psychiatry, Division of Psychology (M.M. Machulda), Mayo Clinic and Foundation, Rochester, MN. knopman@mayo.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.affiliation: From the Departments of Neurology (D.S.K., P.V., M.M. Mielke, R.O.R., B.F.B., D.T.J., R.C.P.) and Radiology (C.R.J., V.J.L., K.K., J.L.G., M.L.S., D.T.J.), Mayo Clinic Alzheimer's Disease Research Center (D.S.K., C.R.J., B.F.B., D.T.J., R.C.P.), Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (H.J.W., S.D.W.), Division of Epidemiology, Department of Health Sciences Research (M.M. Mielke, R.O.R., R.C.P.), and Department of Psychiatry, Division of Psychology (M.M. Machulda), Mayo Clinic and Foundation, Rochester, MN.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: From the Departments of Neurology (D.S.K., P.V., M.M. Mielke, R.O.R., B.F.B., D.T.J., R.C.P.) and Radiology (C.R.J., V.J.L., K.K., J.L.G., M.L.S., D.T.J.), Mayo Clinic Alzheimer's Disease Research Center (D.S.K., C.R.J., B.F.B., D.T.J., R.C.P.), Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (H.J.W., S.D.W.), Division of Epidemiology, Department of Health Sciences Research (M.M. Mielke, R.O.R., R.C.P.), and Department of Psychiatry, Division of Psychology (M.M. Machulda), Mayo Clinic and Foundation, Rochester, MN.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Wiste
authors.affiliation: From the Departments of Neurology (D.S.K., P.V., M.M. Mielke, R.O.R., B.F.B., D.T.J., R.C.P.) and Radiology (C.R.J., V.J.L., K.K., J.L.G., M.L.S., D.T.J.), Mayo Clinic Alzheimer's Disease Research Center (D.S.K., C.R.J., B.F.B., D.T.J., R.C.P.), Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (H.J.W., S.D.W.), Division of Epidemiology, Department of Health Sciences Research (M.M. Mielke, R.O.R., R.C.P.), and Department of Psychiatry, Division of Psychology (M.M. Machulda), Mayo Clinic and Foundation, Rochester, MN.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Weigand
authors.affiliation: From the Departments of Neurology (D.S.K., P.V., M.M. Mielke, R.O.R., B.F.B., D.T.J., R.C.P.) and Radiology (C.R.J., V.J.L., K.K., J.L.G., M.L.S., D.T.J.), Mayo Clinic Alzheimer's Disease Research Center (D.S.K., C.R.J., B.F.B., D.T.J., R.C.P.), Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (H.J.W., S.D.W.), Division of Epidemiology, Department of Health Sciences Research (M.M. Mielke, R.O.R., R.C.P.), and Department of Psychiatry, Division of Psychology (M.M. Machulda), Mayo Clinic and Foundation, Rochester, MN.
authors.forename: Prashanthi
authors.initials: P
authors.lastname: Vemuri
authors.affiliation: From the Departments of Neurology (D.S.K., P.V., M.M. Mielke, R.O.R., B.F.B., D.T.J., R.C.P.) and Radiology (C.R.J., V.J.L., K.K., J.L.G., M.L.S., D.T.J.), Mayo Clinic Alzheimer's Disease Research Center (D.S.K., C.R.J., B.F.B., D.T.J., R.C.P.), Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (H.J.W., S.D.W.), Division of Epidemiology, Department of Health Sciences Research (M.M. Mielke, R.O.R., R.C.P.), and Department of Psychiatry, Division of Psychology (M.M. Machulda), Mayo Clinic and Foundation, Rochester, MN.
authors.forename: Val J
authors.initials: VJ
authors.lastname: Lowe
authors.affiliation: From the Departments of Neurology (D.S.K., P.V., M.M. Mielke, R.O.R., B.F.B., D.T.J., R.C.P.) and Radiology (C.R.J., V.J.L., K.K., J.L.G., M.L.S., D.T.J.), Mayo Clinic Alzheimer's Disease Research Center (D.S.K., C.R.J., B.F.B., D.T.J., R.C.P.), Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (H.J.W., S.D.W.), Division of Epidemiology, Department of Health Sciences Research (M.M. Mielke, R.O.R., R.C.P.), and Department of Psychiatry, Division of Psychology (M.M. Machulda), Mayo Clinic and Foundation, Rochester, MN.
authors.forename: Kejal
authors.initials: K
authors.lastname: Kantarci
authors.affiliation: From the Departments of Neurology (D.S.K., P.V., M.M. Mielke, R.O.R., B.F.B., D.T.J., R.C.P.) and Radiology (C.R.J., V.J.L., K.K., J.L.G., M.L.S., D.T.J.), Mayo Clinic Alzheimer's Disease Research Center (D.S.K., C.R.J., B.F.B., D.T.J., R.C.P.), Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (H.J.W., S.D.W.), Division of Epidemiology, Department of Health Sciences Research (M.M. Mielke, R.O.R., R.C.P.), and Department of Psychiatry, Division of Psychology (M.M. Machulda), Mayo Clinic and Foundation, Rochester, MN.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Gunter
authors.affiliation: From the Departments of Neurology (D.S.K., P.V., M.M. Mielke, R.O.R., B.F.B., D.T.J., R.C.P.) and Radiology (C.R.J., V.J.L., K.K., J.L.G., M.L.S., D.T.J.), Mayo Clinic Alzheimer's Disease Research Center (D.S.K., C.R.J., B.F.B., D.T.J., R.C.P.), Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (H.J.W., S.D.W.), Division of Epidemiology, Department of Health Sciences Research (M.M. Mielke, R.O.R., R.C.P.), and Department of Psychiatry, Division of Psychology (M.M. Machulda), Mayo Clinic and Foundation, Rochester, MN.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Senjem
authors.affiliation: From the Departments of Neurology (D.S.K., P.V., M.M. Mielke, R.O.R., B.F.B., D.T.J., R.C.P.) and Radiology (C.R.J., V.J.L., K.K., J.L.G., M.L.S., D.T.J.), Mayo Clinic Alzheimer's Disease Research Center (D.S.K., C.R.J., B.F.B., D.T.J., R.C.P.), Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (H.J.W., S.D.W.), Division of Epidemiology, Department of Health Sciences Research (M.M. Mielke, R.O.R., R.C.P.), and Department of Psychiatry, Division of Psychology (M.M. Machulda), Mayo Clinic and Foundation, Rochester, MN.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Mielke
authors.affiliation: From the Departments of Neurology (D.S.K., P.V., M.M. Mielke, R.O.R., B.F.B., D.T.J., R.C.P.) and Radiology (C.R.J., V.J.L., K.K., J.L.G., M.L.S., D.T.J.), Mayo Clinic Alzheimer's Disease Research Center (D.S.K., C.R.J., B.F.B., D.T.J., R.C.P.), Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (H.J.W., S.D.W.), Division of Epidemiology, Department of Health Sciences Research (M.M. Mielke, R.O.R., R.C.P.), and Department of Psychiatry, Division of Psychology (M.M. Machulda), Mayo Clinic and Foundation, Rochester, MN.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Machulda
authors.affiliation: From the Departments of Neurology (D.S.K., P.V., M.M. Mielke, R.O.R., B.F.B., D.T.J., R.C.P.) and Radiology (C.R.J., V.J.L., K.K., J.L.G., M.L.S., D.T.J.), Mayo Clinic Alzheimer's Disease Research Center (D.S.K., C.R.J., B.F.B., D.T.J., R.C.P.), Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (H.J.W., S.D.W.), Division of Epidemiology, Department of Health Sciences Research (M.M. Mielke, R.O.R., R.C.P.), and Department of Psychiatry, Division of Psychology (M.M. Machulda), Mayo Clinic and Foundation, Rochester, MN.
authors.forename: Rosebud O
authors.initials: RO
authors.lastname: Roberts
authors.affiliation: From the Departments of Neurology (D.S.K., P.V., M.M. Mielke, R.O.R., B.F.B., D.T.J., R.C.P.) and Radiology (C.R.J., V.J.L., K.K., J.L.G., M.L.S., D.T.J.), Mayo Clinic Alzheimer's Disease Research Center (D.S.K., C.R.J., B.F.B., D.T.J., R.C.P.), Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (H.J.W., S.D.W.), Division of Epidemiology, Department of Health Sciences Research (M.M. Mielke, R.O.R., R.C.P.), and Department of Psychiatry, Division of Psychology (M.M. Machulda), Mayo Clinic and Foundation, Rochester, MN.
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.affiliation: From the Departments of Neurology (D.S.K., P.V., M.M. Mielke, R.O.R., B.F.B., D.T.J., R.C.P.) and Radiology (C.R.J., V.J.L., K.K., J.L.G., M.L.S., D.T.J.), Mayo Clinic Alzheimer's Disease Research Center (D.S.K., C.R.J., B.F.B., D.T.J., R.C.P.), Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (H.J.W., S.D.W.), Division of Epidemiology, Department of Health Sciences Research (M.M. Mielke, R.O.R., R.C.P.), and Department of Psychiatry, Division of Psychology (M.M. Machulda), Mayo Clinic and Foundation, Rochester, MN.
authors.forename: David T
authors.initials: DT
authors.lastname: Jones
authors.affiliation: From the Departments of Neurology (D.S.K., P.V., M.M. Mielke, R.O.R., B.F.B., D.T.J., R.C.P.) and Radiology (C.R.J., V.J.L., K.K., J.L.G., M.L.S., D.T.J.), Mayo Clinic Alzheimer's Disease Research Center (D.S.K., C.R.J., B.F.B., D.T.J., R.C.P.), Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (H.J.W., S.D.W.), Division of Epidemiology, Department of Health Sciences Research (M.M. Mielke, R.O.R., R.C.P.), and Department of Psychiatry, Division of Psychology (M.M. Machulda), Mayo Clinic and Foundation, Rochester, MN.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D000814:Aniline Compounds; D015415:Biomarkers; D002540:Cerebral Cortex / Q000000981:diagnostic imaging*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006624:Hippocampus / Q000000981:diagnostic imaging*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D015415:Biomarkers; D019275:Radiopharmaceuticals; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18