Figure 1. Cross-sectional (A) and longitudinal (B) models for studying cognitive reserve (CR). (A) Measures of brain morphology, integrity or pathology may impact clinical status via path Ⓒ. CR is represented by the orange box; working measures of CR include CR proxies or identified CR brain networks. Age, genetics and life experiences are believed to influence brain measures and CR. CR is assumed to moderate the effect of brain status on clinical status, thus producing individual differences in the clinical correlates of a given level of brain reserve and brain pathology. The effect of brain status on clinical status may be mediated in part by brain networks captured during task related activation (paths Ⓐ and Ⓑ). Path Ⓓ suggest that CR might moderate between brain status and activation. Path Ⓔ recognizes that some aspects of CR might moderate between brain and clinical function without being captured in specific task-related activations. (B) In longitudinal models, two paths can be added: path Ⓕ assesses how CR moderates the effect of brain change on cognitive change, and path Ⓖ addresses neuroprotective mechanisms. Npsy., neuropsychological. Adopted from [