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. 2024 Jan 18;14:34. doi: 10.1038/s41398-024-02755-9

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — A Behavioral experiment schedule of AD mice with metformin treatment. B The survival rate of AD mice (Veh: n = 14, Met: n = 12; p = 0.052; log-rank test) during the behavioral assessment. C The number of trials of 5-month-old AD mice (Veh: n = 13, Met: n = 12; p = 0.988; t test) in the FR schedule. D The breakpoint of 6-month-old AD (Veh: n = 13, Met: n = 12; p = 0.346; RM ANOVA) in the PR schedule. E Accuracy (p = 0.838), (F) omission (p = 0.514), and the number of (G) premature responses (p = 0.732) and perseverative responses to (H) correct stimuli (p = 0.488) and (I) incorrect stimuli (p = 0.090; mixed effects model) of 9-month-old AD mice (Veh: n = 13, Met: n = 12) by SD in the 5-CSRT task. J Accuracy (Main effect of group, p = 0.054; main effect of block, p < 0.001; group by block interaction, p = 0.017; simple effect of group in block 6, p = 0.021; simple effect of group in block 7, p = 0.019; simple effect of group in block 9, p = 0.043) and (K) the number of correction trials (Main effect of group, p = 0.104; main effect of block, p < 0.001; group by block interaction, p < 0.001; simple effect of group in block 5, p = 0.040; simple effect of group in block 6, p = 0.029; simple effect of group in block 7, p = 0.020; simple effect of group in block 9, p = 0.036; mixed effects model) of 13-month-old AD mice (Veh: n = 6, Met: n = 10) in the dPAL task. The block consisted of approximately 300 trials (288–324) as the number of trials per session gradually increased. L Accuracy of 13-month-old AD mice (Veh, n = 6; Met, n = 10; dPAL, p = 0.053; sPAL, p = 0.011; t test) in the sPAL task. M Accuracy of 14-month-old AD mice (Veh, n = 6; Met, n = 10; p < 0.001; mixed effects model) in the retention sessions of sPAL task. The number of (N) trials (p = 0.480) and (O) correction trials (p = 0.379; t test) to accomplish the criterion of 14-month-old AD mice (Veh: n = 9, Met: n = 9) in the VD task. P The number of trials to accomplish the criterion of 14-month-old AD mice (Veh: n = 7, Met: n = 6; p = 0.256; t test) in the reversal task. Q Accuracy of 16-month-old AD mice (Veh: n = 7, Met: n = 6; p = 0.499; mixed effects model) in the reversal retention session. Data are presented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001 versus Veh. AD, 3xTg-AD mice, FR fixed ratio, PR progressive ratio, 5-CSRT 5-choice serial reaction time, PAL paired associates learning, VD visual discrimination, Veh Vehicle, Met Metformin, SD stimulus duration, BL baseline.