Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease Academic Article uri icon

abstract

  • Assess Aβ deposition longitudinally and explore its relationship with cognition and disease progression.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.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.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

  • Villemagne, Victor L
  • Pike, Kerryn E
  • Chételat, Gaël
  • Ellis, Kathryn A
  • Mulligan, Rachel S
  • Bourgeat, Pierrick
  • Ackermann, Uwe
  • Jones, Gareth
  • Szoeke, Cassandra
  • Salvado, Olivier
  • Martins, Ralph
  • O'Keefe, Graeme
  • Mathis, Chester A
  • Klunk, William E
  • Ames, David
  • Masters, Colin L
  • Rowe, Christopher C

publication date

  • January 2011

has subject area