摘要The rising incidence of dementia and associated neurodegenerative disorders poses a growing public health challenge.These conditions have traditionally been studied as isolated central nervous system disorders;however,emerging evidence suggests that broader systemic factors,including chronic inflammation,immune dysregulation,metabolic dysfunction,and genetic susceptibility,may also play a role.This review ex-amines the interconnection between autoimmune diseases and metabolic syndromes in the pathogenesis and exacerbation of neurodegeneration.Conditions such as rheu-matoid arthritis,systemic lupus erythematosus,and type 1 diabetes mellitus have been associated with a heightened risk of developing dementia through chronic immune activation,blood-brain barrier disruption,and neuroinflammatory signaling.Similarly,metabolic disorders such as diabesity promote insulin resistance and oxidative stress,accelerating cognitive decline.The review also discusses glaucoma as a neurodegenera-tive condition with autoimmune features,underscoring the need for expanded classifi-cation and treatment strategies.A key focus is the utilization of the Collaborative Cross(CC)mouse model,which enables the study of gene-environment interactions across genetically diverse backgrounds.Findings from CC mice reveal strain-dependent sus-ceptibility to inflammation,cognitive impairment,and gut-brain axis dysfunction,pro-viding a translational bridge to human variability.This review highlights the importance of integrating precision-based approaches to dementia research that consider systemic influences.Advancing our understanding of these multiorgan interactions holds po-tential for designing precision-based therapeutic approaches to postpone the onset or reduce the incidence of neurodegenerative conditions.