Fig. 2

Absolute ADAS-Cog predictions in an MCI ‘virtual patient’ for different cutoff values for Aβ + and Aβ– imaging SUVR values. Reported ADAS-Cog values are 8.5 for MCI Aβ– patients and 10.8 for MCI Aβ + patients (blue and green horizontal lines, respectively). Cutoff values define the gray area in the Aβ load matrix of Fig. 1. For the optimal parameter set for δ, α, α* and β (x₀ fixed at 2), the average ADAS-Cog prediction for Aβ– and Aβ + MCI subjects is shown by the green triangles and diamonds, respectively. At a cutoff value of 3, both predicted values (7.8 for Aβ– and 10.7 for Aβ + subjects) are near the clinical values. For the situation of δ = 0 (same values for α, α*, β and x₀), the average ADAS-Cog prediction for Aβ– patients and Aβ + patients is shown by the red triangles and diamonds  (8.4 for Aβ– and 14.2 for Aβ + subjects, respectively). In this case, while the Aβ– MCI subjects cross the blue line in the correct range, the Aβ + MCI subjects result in an ADAS-Cog readout that is much greater than the Aβ + reported clinical values (green line). This suggests that the condition δ = 0 (no beneficial effect of Aβ40) is unable to reproduce this clinical outcome. Aβ amyloid-beta, A–β subjects with x ≤ 2 and y ≤ 2, Aβ + subjects with x > 2 and y > 2, ADAS-Cog Alzheimer Disease Assessment Scale, cognitive subscale, MCI minimal cognitive impairment