Fig. 3

Dose–response of scopolamine-mediated cognitive deficits in a MCI population with low and high Aβ load corresponding to 3 units of Aβ load in our model for δ = 0.025, α = 0.002 and α* = 0.002. Slopes for the Aβ– and Aβ + conditions are −1.08 and −1.36% correct answers/nM scopolamine, respectively, for a 2-back working memory (WM) test. Model outcome suggests that higher Aβ load makes the system more sensitive to scopolamine; that is, a greater deficit for the same scopolamine dose that would correspond to the clinically observed slower recovery after scopolamine in MCI subjects. Pharmacodynamic interaction with Aβ can have important consequences as standard of care for AD patients often includes procholinergic compounds. Aβ amyloid-beta, Aβ– subjects with x ≤ 2 and y ≤ 2, Aβ + subjects with x > 2 and y > 2