title: Regional cerebral blood flow estimated by early PiB uptake is reduced in mild cognitive impairment and associated with age in an amyloid-dependent manner.
abstract: Early uptake of [(11)C]-Pittsburgh Compound B (ePiB, 0-6 minutes) estimates cerebral blood flow. We studied ePiB in 13 PiB-negative and 10 PiB-positive subjects with mild cognitive impairment (MCI, n = 23) and 11 PiB-positive and 74 PiB-negative cognitively healthy elderly control subjects (HCS, n = 85) in 6 bilateral volumes of interest: posterior cingulate cortex (PCC), hippocampus (hipp), temporoparietal region, superior parietal gyrus, parahippocampal gyrus (parahipp), and inferior frontal gyrus (IFG) for the associations with cognitive status, age, amyloid deposition, and apolipoprotein E ε4-allele. We observed no difference in ePiB between PiB-positive and -negative subjects and carriers and noncarriers. EPiB decreased with age in PiB-positive subjects in bilateral superior parietal gyrus, bilateral temporoparietal region, right IFG, right PCC, and left parahippocampal gyrus but not in PiB-negative subjects. MCI had lower ePiB than HCS (left PCC, left IFG, and left and right hipp). Lowest ePiB values were found in MCI of 70 years and older, who also displayed high cortical PiB binding. This suggests that lowered regional cerebral blood flow indicated by ePiB is associated with age in the presence but not in the absence of amyloid pathology.
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland. Electronic address: anton.gietl@bli.uzh.ch.
authors.forename: Anton F
authors.initials: AF
authors.lastname: Gietl
authors.affiliation: Department of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Warnock
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Florian
authors.initials: F
authors.lastname: Riese
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Kälin
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Antje
authors.initials: A
authors.lastname: Saake
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Gruber
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Leh
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Unschuld
authors.affiliation: Department of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Felix P
authors.initials: FP
authors.lastname: Kuhn
authors.affiliation: Department of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland; PMOD Technologies Ltd, Zurich, Switzerland.
authors.forename: Cyrill
authors.initials: C
authors.lastname: Burger
authors.affiliation: Department of Nuclear Medicine, Center for Radiopharmaceutical Sciences of ETH-PSI-USZ, University Hospital Zurich, Zurich, Switzerland; Department of Chemistry and Applied Biosciences, Center for Radiopharmaceutical Sciences of ETH-PSI-USZ, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Linjing
authors.initials: L
authors.lastname: Mu
authors.affiliation: Department of Biostatistics, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Seifert
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Roger M
authors.initials: RM
authors.lastname: Nitsch
authors.affiliation: Department of Nuclear Medicine, Center for Radiopharmaceutical Sciences of ETH-PSI-USZ, University Hospital Zurich, Zurich, Switzerland; Department of Chemistry and Applied Biosciences, Center for Radiopharmaceutical Sciences of ETH-PSI-USZ, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: Schibli
authors.affiliation: Department of Chemistry and Applied Biosciences, Center for Radiopharmaceutical Sciences of ETH-PSI-USZ, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Ametamey
authors.affiliation: Department of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Alfred
authors.initials: A
authors.lastname: Buck
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hock
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D000483:Alleles; D058227:Amyloidogenic Proteins / Q000378:metabolism*; D000814:Aniline Compounds / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000098:blood supply* / Q000378:metabolism*; D003071:Cognition; D060825:Cognitive Dysfunction / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow; D013844:Thiazoles / Q000378:metabolism*
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D058227:Amyloidogenic Proteins; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D013844:Thiazoles
keywords: Aging; Alzheimer's disease; Amyloid; Biomarker; Cerebral blood flow; Frontal; Hippocampus; MCI; MRI; PET; PiB; Posterior cingulate cortex