Adaptation of the Concept of Brain Reserve for the Prediction of Stroke Outcome: Proxies, Neural Mechanisms, and Significance for Research

The prediction of stroke outcome is challenging due to the high inter-individual variability in stroke patients. We recently suggested the adaptation of the concept of brain reserve (BR) to improve the prediction of stroke outcome. This concept was initially developed alongside the one for the cognitive reserve for neurodegeneration and forms a valuable theoretical framework to capture high inter-individual variability in stroke patients. In the present work, we suggest and discuss (i) BR-proxies-quantitative brain characteristics at the time stroke occurs (e.g., brain volume, hippocampus volume), and (ii) proxies of brain pathology reducing BR (e.g., brain atrophy, severity of white matter hyperintensities), parameters easily available from a routine MRI examination that might improve the prediction of stroke outcome. Though the influence of these parameters on stroke outcome has been partly reported individually, their independent and combined impact is yet to be determined. Conceptually, BR is a continuous measure determining the amount of brain structure available to mitigate and compensate for stroke damage, thus reflecting individual differences in neural resources and a capacity to maintain performance and recover after stroke. We suggest that stroke outcome might be defined as an interaction between BR at the time stroke occurs and lesion load. BR in stroke can potentially be influenced, e.g., by modifying cardiovascular risk factors. In addition to the potential power of the BR concept in a mechanistic understanding of inter-individual variability in stroke outcome and establishing individualized therapeutic approaches, it might help to strengthen the synergy of preventive measures in stroke, neurodegeneration, and healthy aging.