title: Amyloid-first and neurodegeneration-first profiles characterize incident amyloid PET positivity.
abstract: OBJECTIVE
  To estimate the incidence of and to characterize cognitive and imaging findings associated with incident amyloid PET positivity.
  
  
  METHODS
  Cognitively normal (CN) participants in the Mayo Clinic Study of Aging who had 2 or more serial imaging assessments, which included amyloid PET, FDG-PET, and MRI at each time point, were eligible for analysis (n = 207). Twelve subjects with Alzheimer disease dementia were included for comparison.
  
  
  RESULTS
  Of the 123 CN participants who were amyloid-negative at baseline, 26 met criteria for incident amyloid PET positivity. Compared to the 69 subjects who remained stable amyloid-negative, on average these 26 did not differ on any imaging, demographic, or cognitive variables except amyloid PET (by definition) and task-free functional connectivity, which at baseline was greater in the incident amyloid-positive group. Eleven of the 26 incident amyloid-positive subjects had abnormal hippocampal volume, FDG-PET, or both at baseline.
  
  
  CONCLUSIONS
  The incidence of amyloid PET positivity is approximately 13% per year among CN participants over age 70 sampled from a population-based cohort. In 15/26 (58%), incident amyloid positivity occurred prior to abnormalities in FDG-PET and hippocampal volume. However, 11/26 (42%) incident amyloid-positive subjects had evidence of neurodegeneration prior to incident amyloid positivity. These 11 could be subjects with combinations of preexisting non-Alzheimer pathophysiologies and tau-mediated neurodegeneration who newly entered the amyloid pathway. Our findings suggest that both "amyloid-first" and "neurodegeneration-first" biomarker profile pathways to preclinical AD exist.
authors.affiliation: From the Departments of Radiology (C.R.J., V.L., P.V., D.T.J., M.L.S., J.L.G., B.E.G.), Health Sciences Research (H.J.W., S.D.W., M.M.M., V.S.P.), and Neurology (D.S.K., R.C.P.), Mayo Clinic and Foundation, Rochester, MN.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Wiste
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Weigand
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.forename: Val
authors.initials: V
authors.lastname: Lowe
authors.forename: Prashanthi
authors.initials: P
authors.lastname: Vemuri
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Mielke
authors.forename: David T
authors.initials: DT
authors.lastname: Jones
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Senjem
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Gunter
authors.forename: Brian E
authors.initials: BE
authors.lastname: Gregg
authors.forename: Vernon S
authors.initials: VS
authors.lastname: Pankratz
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000000981:diagnostic imaging; D000682:Amyloid / Q000378:metabolism*; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology; D005260:Female; D019788:Fluorodeoxyglucose F18; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D015994:Incidence; D008279:Magnetic Resonance Imaging; D008297:Male; D019636:Neurodegenerative Diseases / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism*; D010100:Oxygen; D049268:Positron-Emission Tomography
chemical_list: D000682:Amyloid; D019788:Fluorodeoxyglucose F18; D010100:Oxygen