title: Evolution of neurodegeneration-imaging biomarkers from clinically normal to dementia in the Alzheimer disease spectrum.
abstract: The availability of antemortem biomarkers for Alzheimer's disease (AD) enables monitoring the evolution of neurodegenerative processes in real time. Pittsburgh compound B (PIB) positron emission tomography (PET) was used to select participants in the Mayo Clinic Study of Aging and the Mayo Alzheimer's Disease Research Center with elevated β-amyloid, designated as "A+," and hippocampal volume and (18)fluorodeoxyglucose (FDG) positron emission tomography were used to characterize participants as having evidence of neurodegeneration ("N+") at the baseline evaluation. There were 145 clinically normal (CN) A+ individuals, 62 persons with mild cognitive impairment (MCI) who were A+ and 20 with A+ AD dementia. Over a period of 1-6 years, MCI A+N+ individuals showed declines in medial temporal, lateral temporal, lateral parietal, and to a lesser extent, medial parietal regions for both FDG standardized uptake value ratio and gray matter volume that exceeded declines seen in the CN A+N+ group. The AD dementia group showed declines in the same regions on FDG standardized uptake value ratio and gray matter volume with rates that exceeded that in MCI A+N+. Expansion of regional involvement and faster rate of neurodegeneration characterizes progression in the AD pathway.
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, Rochester, MN, USA; Mayo Clinic Alzheimer's Disease Research Center, Mayo Clinic and Foundation, Rochester, MN, USA. Electronic address: knopman@mayo.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.affiliation: Mayo Clinic Alzheimer's Disease Research Center, Mayo Clinic and Foundation, Rochester, MN, USA; Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Lundt
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Weigand
authors.affiliation: Mayo Clinic Alzheimer's Disease Research Center, Mayo Clinic and Foundation, Rochester, MN, USA; Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Prashanthi
authors.initials: P
authors.lastname: Vemuri
authors.affiliation: Mayo Clinic Alzheimer's Disease Research Center, Mayo Clinic and Foundation, Rochester, MN, USA; Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Val J
authors.initials: VJ
authors.lastname: Lowe
authors.affiliation: Mayo Clinic Alzheimer's Disease Research Center, Mayo Clinic and Foundation, Rochester, MN, USA; Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Kejal
authors.initials: K
authors.lastname: Kantarci
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA; Department of Information Technology, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Gunter
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA; Department of Information Technology, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Senjem
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, Rochester, MN, USA; Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Mielke
authors.affiliation: Mayo Clinic Alzheimer's Disease Research Center, Mayo Clinic and Foundation, Rochester, MN, USA; Department of Psychiatry, Division of Psychology, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Machulda
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, Rochester, MN, USA; Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Rosebud O
authors.initials: RO
authors.lastname: Roberts
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, Rochester, MN, USA; Mayo Clinic Alzheimer's Disease Research Center, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, Rochester, MN, USA; Mayo Clinic Alzheimer's Disease Research Center, Mayo Clinic and Foundation, Rochester, MN, USA; Department of Radiology, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Jones
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, Rochester, MN, USA; Mayo Clinic Alzheimer's Disease Research Center, Mayo Clinic and Foundation, Rochester, MN, USA; Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D010296:Parietal Lobe / Q000000981:diagnostic imaging / Q000473:pathology; D049268:Positron-Emission Tomography; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000473:pathology
keywords: Alzheimer's disease; FDG PET imaging; Longitudinal study; MR imaging; PIB PET imaging