title: Role of β-Amyloidosis and Neurodegeneration in Subsequent Imaging Changes in Mild Cognitive Impairment.
abstract: OBJECTIVE
  To understand how a model of Alzheimer disease pathophysiology based on β-amyloidosis and neurodegeneration predicts the regional anatomic expansion of hypometabolism and atrophy in persons with mild cognitive impairment (MCI).
  
  
  OBJECTIVE
  To define the role of β-amyloidosis and neurodegeneration in the subsequent progression of topographic cortical structural and metabolic changes in MCI.
  
  
  METHODS
  Longitudinal, observational study with serial brain imaging conducted from March 28, 2006, to January 6, 2015, using a population-based cohort. A total of 96 participants with MCI (all aged >70 years) with serial imaging biomarkers from the Mayo Clinic Study of Aging or Mayo Alzheimer's Disease Research Center were included. Participants were characterized initially as having elevated or not elevated brain β-amyloidosis (A+ or A-) based on 11C-Pittsburgh compound B positron emission tomography. They were further characterized initially by the presence or absence of neurodegeneration (N+ or N-), where the presence of neurodegeneration was defined by abnormally low hippocampal volume or hypometabolism in an Alzheimer disease-like pattern on 18fluorodeoxyglucose (FDG)-positron emission tomography.
  
  
  METHODS
  Regional FDG standardized uptake value ratio (SUVR) and gray matter volumes in medial temporal, lateral temporal, lateral parietal, and medial parietal regions.
  
  
  RESULTS
  In the primary regions of interest (ROI), the A+N+ group (n = 45) had lower FDG SUVR at baseline compared with the A+N- group (n = 17) (all 4 ROIs; P < .001). The A+N+ group also had lower FDG SUVR at baseline (all 4 ROIs; P < .01) compared with the A-N- group (n = 12). The A+N+ group had lower medial temporal gray matter volume at baseline (P < .001) compared with either the A+N- group or A-N- group. The A+N+ group showed large longitudinal declines in FDG SUVR (P < .05 for medial temporal, lateral temporal, and medial parietal regions) and gray matter volumes (P < .05 for medial temporal and lateral temporal regions) compared with the A-N+ group (n = 22). The A+N+ group also showed large longitudinal declines compared with the A-N- group on FDG SUVR (P < .05 for medial temporal and lateral parietal regions) and gray matter volumes (all 4 ROIs; P < .05) compared with the A+N- group. The A-N+ group did not show declines in FDG SUVR or gray matter volume compared with the A+N- or A-N- groups.
  
  
  CONCLUSIONS
  Persons with MCI who were A+N+ demonstrated volumetric and metabolic worsening in temporal and parietal association areas, consistent with the expectation that the MCI stage in the Alzheimer pathway heralds incipient isocortical involvement. The A-N+ group, those with suspected non-Alzheimer pathophysiology, lacked a distinctive longitudinal volumetric or metabolic profile.
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, Rochester, Minnesota2Mayo Clinic Alzheimer's Disease Research Center, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.affiliation: Mayo Clinic Alzheimer's Disease Research Center, Mayo Clinic and Foundation, Rochester, Minnesota3Department of Radiology, Mayo Clinic and Foundation, Rochester, Minnesota.
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, Minnesota.
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, Minnesota.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Wiste
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Weigand
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Prashanthi
authors.initials: P
authors.lastname: Vemuri
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Val J
authors.initials: VJ
authors.lastname: Lowe
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Kejal
authors.initials: K
authors.lastname: Kantarci
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Gunter
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Senjem
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, Rochester, Minnesota5Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Mielke
authors.affiliation: Division of Psychology, Department of Psychiatry, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Machulda
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, Rochester, Minnesota5Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Rosebud O
authors.initials: RO
authors.lastname: Roberts
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, Rochester, Minnesota2Mayo Clinic Alzheimer's Disease Research Center, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, Rochester, Minnesota2Mayo Clinic Alzheimer's Disease Research Center, Mayo Clinic and Foundation, Rochester, Minnesota3Department of Radiology, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: David T
authors.initials: DT
authors.lastname: Jones
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, Rochester, Minnesota2Mayo Clinic Alzheimer's Disease Research Center, Mayo Clinic and Foundation, Rochester, Minnesota5Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic and F.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications*; D000686:Amyloidosis / Q000150:complications*; D000814:Aniline Compounds / Q000493:pharmacokinetics; D060825:Cognitive Dysfunction / Q000175:diagnosis* / Q000209:etiology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D008297:Male; D019636:Neurodegenerative Diseases / Q000150:complications*; D049268:Positron-Emission Tomography; D013844:Thiazoles / Q000493:pharmacokinetics
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18