One hundred forty six participants () underwent two PIB PET scans within 1 to 5 years (mean interval 2.6 ± 1.1 years) (). A family history of AD, was present in 89 of 146 (61.0%) participants but was not associated (independent of APOE4) with the rate of Aβ accumulation in MCBP or with the BP of any individual ROIs (F(1, 142)= 1.38, p= 0.2412).
In 21 (High-PIB, 13 females, mean age 69.0 ± 6.7 years) of the 146 participants, both PIB scans were positive (MCBP>0.18). From first to second PIB scans, 17 of the 21 (81%) High-PIB individuals showed subsequent increase in Aβ accumulation and 4 individuals (3 were 80 years or older) had decreases in MCBP and regional BP. The mean MCBP at first scan in the High-PIB group was 0.44 ± 0.20, with a mean change of 0.091 ± 0.106. This translated to a MCBP annual increase of 0.035 ± 0.040, or approximately 8% per year. The High-PIB group did not differ significantly in age from the Low-PIB group (MCBP < 0.18, n=125, 86 females, mean age 65.5 ± 10.7 years) at initial scan (F(1, 144)= 2.10, p= 0.1498), but demonstrated higher age-adjusted rate of Aβ accumulation for all ROIs except for anterior cingulate, occipital cortex and caudate. Age at initial scan was not associated with the rate of change in MCBP in the Low-PIB group (t(142)=0.58, p= 0.5635). In the High-PIB group, the rate of Aβ accumulation decreased slightly (but significantly) as a function of age at the first PIB scan (t(142)= −4.07, p <.0001), primarily driven by the 3 oldest individuals (>80 y) whose rate of change in MCBP was negative ().
Ten (7 females, mean age 65.5 ± 8.3 years) of the 125 (8.0%) Low-PIB individuals became positive on the second PIB scan, yielding an incidence of conversion from normal to abnormal Aβ burden of 3.1% per year. Including the second scan, 31 of the 146 (21%) cognitively normal individuals had elevated PIB retention. The youngest participant to convert was 56 yrs at the second PIB scan. Seven of the 10 converters were APOE4 positive.
Fifty participants () had at least one APOE ε4 allele. Thirteen (61.9%) individuals in the High-PIB group were APOE4 carriers versus 37 (29.6%) in the Low-PIB group. The incidence of conversion from negative to positive PIB scan in APOE4 individuals was 7.0% per year, more than double that of the entire group (3.1%/yr). With age as a covariate, APOE4 was unassociated with rate of change in MCBP and in the BP of any individual ROI. When the 3 oldest individuals (> 80 y)with decreases in MCBP and regional BP were removed from the analysis, however, the rate of Aβ accumulation in the precuneus was associated with APOE4 (0.010 ± 0.037 BP/yr for APOE4−; 0.026 ± 0.040 BP/yr for APOE4+; F(1,139)= 8.86,p= 0.0034). A similar association was observed in the precuneus when the analyses (adjusting for age) were limited to individuals (absent the 3 oldest) in the High-PIB group (0.016 ± 0.020 BP/yr for APOE4−; 0.065 ± 0.032 BP/yr for APOE4+; t(139)= −2.83, p= 0.0053).