Research progress on the mechanisms of neurosyphilis’ impact on cognitive function, early identification, and prevention strategies

Neurosyphilis, a severe and often neglected complication of <i>Treponema pallidum</i> infection, poses a significant global public health threat, particularly impacting marginalized populations such as men who have sex with men and people with human immunodeficiency virus. Despite global efforts to control syphilis, neurosyphilis is increasingly prevalent, with documented surges of >700% in some regions. Its role in driving cognitive decline often misdiagnosed as psychiatric or neurodegenerative disorders exemplifies "neglected" dimension of diseases. This narrative review synthesizes recent advances in understanding its role in cognitive impairment, spanning from mild deficits to dementia. We detail the multifaceted pathophysiology, including blood-brain barrier disruption, neuroinflammation, abnormal protein aggregation, cerebral small vessel disease, and metabolic dysfunction, which collectively drive neurodegeneration. Critically, we highlight challenges in early diagnosis due to non-specific symptoms and limitations of traditional tests and promising solutions are presented. We also explore novel therapeutic targets and essential public health measures. This comprehensive discussion aims to enhance our understanding the role of neurosyphilis in driving cognitive impairment and potentially contribute to the development of more effective prevention and management strategies.