Programmed cell death in dementia: advances in pathogenesis and therapeutic strategies

Dementia comprises a group of neurodegenerative disorders characterized primarily by progressive cognitive decline. Its central pathological feature is the irreversible loss of neurons, which leads to the continuous deterioration of memory, language, and executive functions. In recent years, programmed cell death (PCD), as a major form of regulated cell death, has attracted increasing attention because of its critical involvement in neuronal loss during the development of dementia. Accumulating evidence has demonstrated that multiple forms of PCD, including apoptosis, autophagic cell death, necroptosis, pyroptosis, and ferroptosis, are aberrantly activated in common dementia subtypes such as Alzheimer’s disease (AD) and vascular dementia (VaD), where they synergistically promote neurodegeneration through distinct molecular mechanisms. However, therapeutic interventions targeting a single PCD pathway are often insufficient to halt disease progression, and the pathological heterogeneity among different dementia subtypes further complicates treatment. This review systematically summarizes the molecular mechanisms and pathological contributions of the major forms of PCD in dementia and further discusses emerging therapeutic strategies targeting PCD pathways, including small-molecule inhibitors, genetic modulation, and nanomedicine-based drug delivery systems. By integrating recent advances in this field, this review aims to provide a theoretical framework and translational perspectives for the development of early diagnostic biomarkers and precision therapeutic strategies for dementia.