title: Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease.
abstract: OBJECTIVE
  Assess Aβ deposition longitudinally and explore its relationship with cognition and disease progression.
  
  
  METHODS
  Clinical follow-up was obtained 20 ± 3 months after [¹¹C]Pittsburgh compound B (PiB)-positron emission tomography in 206 subjects: 35 with dementia of the Alzheimer type (DAT), 65 with mild cognitive impairment (MCI), and 106 age-matched healthy controls (HCs). A second PiB scan was obtained at follow-up in 185 subjects and a third scan after 3 years in 57.
  
  
  RESULTS
  At baseline, 97% of DAT, 69% of MCI, and 31% of HC subjects showed high PiB retention. At 20-month follow-up, small but significant increases in PiB standardized uptake value ratios were observed in the DAT and MCI groups, and in HCs with high PiB retention at baseline (5.7%, 2.1%, and 1.5%, respectively). Increases were associated with the number of apolipoprotein E ε4 alleles. There was a weak correlation between PiB increases and decline in cognition when all groups were combined. Progression to DAT occurred in 67% of MCI with high PiB versus 5% of those with low PiB, but 20% of the low PiB MCI subjects progressed to other dementias. Of the high PiB HCs, 16% developed MCI or DAT by 20 months and 25% by 3 years. One low PiB HC developed MCI.
  
  
  CONCLUSIONS
  Aβ deposition increases slowly from cognitive normality to moderate severity DAT. Extensive Aβ deposition precedes cognitive impairment, and is associated with ApoE genotype and a higher risk of cognitive decline in HCs and progression from MCI to DAT over 1 to 2 years. However, cognitive decline is only weakly related to change in Aβ burden, suggesting that downstream factors have a more direct effect on symptom progression.
authors.affiliation: Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Australia. villemagne@petnm.unimelb.edu.au
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.forename: Kerryn E
authors.initials: KE
authors.lastname: Pike
authors.forename: Gaël
authors.initials: G
authors.lastname: Chételat
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Ellis
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Mulligan
authors.forename: Pierrick
authors.initials: P
authors.lastname: Bourgeat
authors.forename: Uwe
authors.initials: U
authors.lastname: Ackermann
authors.forename: Gareth
authors.initials: G
authors.lastname: Jones
authors.forename: Cassandra
authors.initials: C
authors.lastname: Szoeke
authors.forename: Olivier
authors.initials: O
authors.lastname: Salvado
authors.forename: Ralph
authors.initials: R
authors.lastname: Martins
authors.forename: Graeme
authors.initials: G
authors.lastname: O'Keefe
authors.forename: Chester A
authors.initials: CA
authors.lastname: Mathis
authors.forename: William E
authors.initials: WE
authors.lastname: Klunk
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Rowe
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000175:diagnosis*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D058225:Plaque, Amyloid / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000473:pathology*; D011110:Polymorphism, Genetic; D049268:Positron-Emission Tomography; D012720:Severity of Illness Index; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D013844:Thiazoles