A core unifying biomarker underlying heterogeneous non-pharmacological interventions that attenuate age-related cognitive decline and its causal validation

Abstract:  Addressing the critical public health need for the prevention and treatment of age-related cognitive decline and related neurodegenerative diseases in the context of population aging, the present study focuses on non-pharmacological interventions as a promising strategy for mitigating cognitive deterioration in older adults. We aim to identify a core unifying neural biomarker underlying heterogeneous interventions and to establish causal evidence for its role through three integrated studies. Study 1 utilizes multimodal data from different types of interventions (including behavioral and neuroimaging data) to propose the novel hypothesis of a “core convergent network”. Based on this framework, we will identify and characterize the shared neural biomarker across different non-pharmacological interventions through multidimensional analyses of functional gradients, intrinsic neural timescales, and brain asymmetry. Studies 2 and 3 employ repetitive transcranial magnetic stimulation (rTMS) to modulate the core brain network identified in Study 1. Combined with task-based functional magnetic resonance imaging and behavioral experiment, these studies will provide dual validation in healthy and pathological aging, thereby establishing a complete research framework from mechanistic investigation to causal verification. The expected outcomes will reveal common patterns of neuroplasticity across intervention types and provide an original theoretical basis for developing precision intervention strategies based on a core unifying neural biomarker in older adults. The findings will have important scientific value for improving healthy aging management and reducing the burden of dementia and related disorders, while supporting national strategic initiatives such as “Active Response to Population Aging” and “Healthy China 2030”.