Broadening the scope of multimodal precision prevention in Alzheimer’s disease research

Introduction Within the last decade, translational research into Alzheimer’s disease and related dementias (ADRD) has embraced the complexity of disease mechanisms and pluralistic approaches to therapeutics. As part of this broader shift, the “multimodal precision prevention paradigm” has emerged as an actionable approach to reduce the public health burden of ADRD. Objective To provide an overview of the definitions, scope, and limitations of the multimodal precision prevention paradigm for ADRD and propose a broader definition of translational research in ADRD research and policy. Methods This article performs a critical analysis of leading proposals by different international research initiatives working on multimodal precision medicine for ADRD prevention. Main results Within the multimodal precision prevention paradigm, two overlapping approaches are distinguished on a continuum: on one hand, researchers predominantly from the global North propose a multimodal therapy approach. On the other hand, authors from the global South are proposing a “multimodal diversity” approach stressing the need for a deeper understanding of, and action against, broader contributors to risk of ADRD. It is argued that the complexity of multimodal diversity requires extending the scope of what is typically called “translational research” beyond the “bench-to-bedside” metaphor to include broader policy entry points for prevention (such as action against the social determinants of ADRD). Conclusions Translational research into ADRD faces a choice between narrow and broader policy entry points. This article suggests a broader definition of translational research as follows: translational research in Alzheimer’s disease and Alzheimer’s disease-related dementias should promote a multi-directional interaction between, and multimodal integration of, laboratory-based and diverse population research to achieve a robust, global understanding of brain health and disease that can inspire equitable public health policy and advance precision medicine.