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. 2020 Mar 12;139(6):1025–1044. doi: 10.1007/s00401-020-02138-6

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© The Author(s) 2020

Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — Effect of p.P522R on the cognitive decline in 3,595 MCI patients. a Predicted trajectories of cognitive decline for p.P522R carrier and non-carrier in the pooled sample of all MCI patients. b Predicted trajectories of cognitive decline for p.P522R carrier and non-carrier in the Fundacio ACE (FACE) cohort. c Predicted trajectories of cognitive decline for p.P522R carrier and non-carrier in the German study on aging, cognition, and dementia (AgeCoDe) cohort. d Predicted trajectories of cognitive decline for p.P522R carrier and non-carrier in the Dementia competence network (DCN) cohort. e Predicted trajectories of cognitive decline for p.P522R carrier and non-carrier in the ADNI cohort. Predicted trajectories for the Amsterdam dementia cohort (ADC) are displayed in supplementary figure 1, online resource due to the unreasonably low number of p.P522R carriers with sufficient follow-up. f Effect of p.P522R and APOE-ε4 on the cognitive change from baseline in the MMSE derived from a linear mixed model with a latent process including an interaction term between APOE-ε4 and p.P522R. Differences on the latent process scale between APOE-ε4 carrier and non-carrier who do not carry the pP522R variant were derived to assess the effect size of APOE-ε4 (red arrow in Fig. 2f and red dots in Fig. 2g, h). The difference between p.P522R carrier and non-carrier in the absence (magenta arrows in Fig. 2f and magenta dots in Fig. 2g) and the presence of APOE-ε4 (green arrows in fig. 2f and green dots in Fig. 2h) were calculated, as well. g The effect size of the association of not carrying any APOE-ε4 allele (red dots) and p.P522R in the presence of APOE-ε4 (green dots) with the cognitive change at different time points. Effect sizes are displayed on the scale of the latent process of the mixed model standardized by the expected variance of the latent process at the last time point considered (see supplementary text 6.2, online resource). h The effect size of the association of not carrying any APOE-ε4 allele (red dots) and p.P522R in the absence of APOE-ε4 (magenta dots) with the cognitive change at different time points. Effect sizes are displayed on the scale of the latent process of the mixed model standardized by the expected variance of the latent process at the last time point considered (see supplementary text 6.2, online resource)