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. 2020 Sep 11;8:562662. doi: 10.3389/fcell.2020.562662

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Copyright © 2020 Dunn, Hadad, Neuner, Zhang, Philip, Dumitrescu, Hohman, Herskowitz, O’Connell and Kaczorowski.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Complex cognitive trajectories in aging may be modeled in the B6-BXD mice. (A) Visualization of idealized data exemplifying cognitive functional decline in normal aging (gradual decline after midlife; black line), dementia (rapid decline to impairment in midlife; red line), cognitive reserve (higher baseline; pink line), cognitive resilience (slower decline; blue line), or both cognitive reserve and resilience (green line). Individuals with intellectual disability or impaired performance at baseline (orange line) are typically excluded from human studies in cognitive aging. (B,C) We identified strains displaying suggestive reserve and/or resilience on individual cognitive measures; these strains remain only suggestively in their categories because, though strain averages fall within the limits of our definitions, within-strain variability exceeded our margins of error in every case. For individual traits, B6-BXD100 and B6-BXD56 were suggestive resilient strains, and B6-BXD69 and B6-BXD61 were suggestive reserve + resilient strains in y-maze. B6-BXD68 was a suggestive resilient strain, and B6-BXD51 and B6 homozygotes were suggestive reserve + resilient strains in CFM. Right panels: We also calculated a composite score for cognitive performance across three traits (y-maze, CFA, and CFM) by summing the z-score for each trait within each strain. B6-BXD68 was a suggestive resilient strain, and B6-BXD51 and B6-BXD56 were suggestive reserve strains. (D) Strains that had baseline (6 months) performance below the 3rd Quartile (i.e., no cognitive reserve), midlife (14 months) performance below the median (i.e., insufficient cognitive reserve), or a greater than average rate of decline (i.e., no cognitive resilience) were considered “normal agers”. For (B–E), color scheme is as in (A). Black dashed line is median, gray dashed lines are 1st and 3rd quartile. For ease of visualization, each category of aging trajectory was visualized separately. Strains with n < 2 at either time point were excluded from categorization and visualization. (E) Strains with baseline performance below the 1st quartile were considered impaired.