title: Brain β-amyloid load approaches a plateau.
abstract: OBJECTIVE
  To model the temporal trajectory of β-amyloid accumulation using serial amyloid PET imaging.
  
  
  METHODS
  Participants, aged 70-92 years, were enrolled in either the Mayo Clinic Study of Aging (n = 246) or the Mayo Alzheimer's Disease Research Center (n = 14). All underwent 2 or more serial amyloid PET examinations. There were 205 participants classified as cognitively normal and 55 as cognitively impaired (47 mild cognitive impairment and 8 Alzheimer dementia). We measured baseline amyloid PET-relative standardized uptake values (SUVR) and, for each participant, estimated a slope representing their annual amyloid accumulation rate. We then fit regression models to predict the rate of amyloid accumulation given baseline amyloid SUVR, and evaluated age, sex, clinical group, and APOE as covariates. Finally, we integrated the amyloid accumulation rate vs baseline amyloid PET SUVR association to an amyloid PET SUVR vs time association.
  
  
  RESULTS
  Rates of amyloid accumulation were low at low baseline SUVR. Rates increased to a maximum at baseline SUVR around 2.0, above which rates declined-reaching zero at baseline SUVR above 2.7. The rate of amyloid accumulation as a function of baseline SUVR had an inverted U shape. Integration produced a sigmoid curve relating amyloid PET SUVR to time. The average estimated time required to travel from an SUVR of 1.5-2.5 is approximately 15 years.
  
  
  CONCLUSIONS
  This roughly 15-year interval where the slope of the amyloid SUVR vs time curve is greatest and roughly linear represents a large therapeutic window for secondary preventive interventions.
authors: From the Departments of Radiology, Mayo Clinic, Rochester, MN, USA. jack.clifford@mayo.edu
authors: Clifford R
authors: CR
authors: Jack
authors: Heather J
authors: HJ
authors: Wiste
authors: Timothy G
authors: TG
authors: Lesnick
authors: Stephen D
authors: SD
authors: Weigand
authors: David S
authors: DS
authors: Knopman
authors: Prashanthi
authors: P
authors: Vemuri
authors: Vernon S
authors: VS
authors: Pankratz
authors: Matthew L
authors: ML
authors: Senjem
authors: Jeffrey L
authors: JL
authors: Gunter
authors: Michelle M
authors: MM
authors: Mielke
authors: Val J
authors: VJ
authors: Lowe
authors: Bradley F
authors: BF
authors: Boeve
authors: Ronald C
authors: RC
authors: Petersen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D049268:Positron-Emission Tomography
chemical_list: D016229:Amyloid beta-Peptides