Behavioral analysis.

<p>Barnes maze testing was used to longitudinally examine the effects of IDT on learning and memory at 11.5 months (A-C) and 16 months (D-F) of age. Four days of training was followed 48 hrs later by a retention probe trial. There were no significant differences in average speed at either time point examined (A/D). At 11.5 months of age, all treatment groups were able to learn the location of the escape hole (B). Repeated measures two-way ANOVA of the acquisition phase revealed a significant effect of time (F<sub>3, 195</sub> = 17.06, P < 0.001) and treatment (F<sub>4, 195</sub> = 7.8, P < 0.001). NonTg mice performed significantly better than Con 3xTgAD mice (*p< 0.05, **p<0.01, ***p<0.001). One-way ANOVA of the 48 hr retention probe trial (C) revealed a significant treatment effect on memory retention (F<sub>4, 71</sub> = 6.184, P < 0.0001). Low IDT treatment significantly improved spatial memory retention compared to Con 3xTgAD mice (*p < 0.05). NonTg performance on the probe trial was also significantly improved from Con 3xTgAD mice (***p < 0.001). Data represent mean ± SEM of n = 14-15/group. At 16 months of age, all treatment groups were again able to learn the location of the escape hole. Repeated measure two-way ANOVA of the acquisition phase (E) revealed a significant effect of time (F<sub>3, 126</sub> = 17.06, P < 0.001) and treatment (F<sub>4, 126</sub> = 11.65, P < 0.001). The interaction of Time x Treatment was significant (F<sub>12, 126</sub> = 3.18, P = 0.005). NonTg and IDT treated mice had improved performance compared to Con 3xTgAD mice (*p< 0.05, **p<0.01, ***p<0.001). One-way ANOVA of the 48 hr retention probe trial (F) revealed a significant treatment effect on memory retention (F<sub>4, 43</sub> = 4.538, P = 0.0042). NonTg and Low IDT mice performed significantly better on the spatial memory retention trial compared to Con 3xTgAD mice (*p < 0.05) with Med IDT mice also showing improved performance. Data represent mean ± SEM of n = 6-14/group. (G) Nesting behavior. Mice were given nesting materials and 24 hrs to build a nest. Nests were scored on a scale from 0–5. All IDT doses improved scores vs. Con 3xTgAD mice (***p < 0.001). Data represent mean ± SEM of n = 12–14/group.</p>