Improving the resistance and resilience framework for aging and dementia studies

Background: The "resistance vs resilience" to Alzheimer's disease (AD) framework (coping vs avoiding) has gained interest in the field in the last year. In this viewpoint, our effort is (i) to provide clarity to the usage of the framework in the context of the ATN (amyloid/tau/neurodegeneration) system as well as in lifespan and cognitive aging studies and (ii) to discuss the challenges of matching these concepts to specific biological mechanisms.

Main body: In the context of the ATN system, the main goal of the resistance vs resilience framework is to make a fundamental distinction between risk factors that may help halt the development of AD pathologies (AT) ("resistance") vs delay processes downstream to AT, i.e., neurodegeneration (N) and the clinical expression of the disease ("resilience"). The process of resilience in dementia and aging research should be envisioned as a process that is developed over the lifespan. Greater neurobiological capital to start with (initial brain reserve), maintaining brain structure and function (brain maintenance), or greater adaptability of cognitive strategies to perform a task (cognitive reserve) could all contribute to higher resilience to pathologies later in life. Simply put, resilience is not only a response to pathological processes (i.e. increased brain function to compensate for increasing AD pathology) but also reflects individual differences in brain structure and function that can be built over the lifespan (e.g., through education, lifetime cognitive, and physical activities). Further, the resistance vs resilience terminology can be extended to study other pathological processes such as cerebrovascular lesions, Lewy body disease, or TDP-43. However, some challenges do exist: (i) when studying multiple neuropathologies, the study design and framework will drive the usage of terminology; (ii) it is unavoidable that the measurements of resilience (brain structure and function) will reflect both the effect of pathologies and the impact of several risk and protective factors throughout the lifespan. Therefore, identifying resilience brain markers across lifespan, aging, and dementia studies, notably with longitudinal study designs, will be an important step towards understanding mechanisms of action.

Conclusions: While the field advances towards consensus definitions of existing concepts, the resistance vs resilience terminology may provide clarity in the communication of results in aging and dementia studies as well as provide a framework for the development of both hypotheses and study designs.