Theoretical and practical challenges for capturing reserve and resilience in aging and Alzheimer's disease: A narrative review.

The concepts of reserve and resilience in aging and Alzheimer's disease (AD) are widely used but their operationalization remains challenging and often lacks conceptual and methodological consistency. In this narrative review, we describe the chronological history of these concepts and then summarize and discuss key theoretical and practical issues, along with proposed solutions and different perspectives, in the context of aging and AD. Theoretical challenges include risk versus protective factors, dynamic brain and cognitive trajectories, overestimation of resilience and inflection points. Practical challenges include proxy measures, study designs, residual approaches, and influential cases. We highlight the need for greater methodological harmonization, improved validation of proxy, and lifespan longitudinal approaches. Addressing these challenges will strengthen interpretability, reproducibility, and causal inference, ultimately facilitating the translation of reserve and resilience research into preventive and therapeutic strategies.