Background: We performed PET [11C] PIB scans on cognitive normal subjects in both a cross-sectional and
longitudinal design to estimate the prevalence and incidence of Aβ plaques, as well as the rate of accumulation.
Methods: Cognitively normal (CDR 0) subjects (45 to 88 yrs) underwent one (n=241) or two (n=129; separated by
2.5±1.1 years) PET [11C] PIB scans. Binding Potential (BP) values and a global estimate of Aβ plaque deposition,
the mean cortical BP (MCBP), were estimated in MRI-derived regions. The rate of Aβ accumulation was estimated
from the change in BP per year.
Results: Using a threshold of MCBP >0.18, prevalence of Aβ plaques were seen to increase with age from 4.4% in
the 50-59 decade to 30% in the 80-89 decade. Longitudinal analysis showed that 8 of the 110 subjects (7.3%) with
a negative initial scan became positive on the second PIB scan yielding an incidence of 2.9%/yr. Subjects with at
least one abnormal PIB scan (n=29) had a significantly higher rate of Aβ accumulation compared to the remaining
subjects (0.034 BP/yr vs 0.008 BP/yr; p<0.001). Using a simple decay model and the estimated incidence of
2.9%/yr, the observed prevalence of Aβ plaques in each decade was predicted with surprising accuracy using a
mean time between appearance of Aβ plaques to dementia of 10.8 years.
Conclusions: [11C] PIB can detect accumulation of Aβ in cognitively normal subjects. These results suggest
that combining longitudinal and cross-sectional Aβ imaging may characterize the onset and progression of a
preclinical AD state to dementia.