Central Sensitization Syndromes as a Neuropsychiatric Risk State for Dementia: Clinical and Epidemiologic Perspectives

BackgroundDementia prevention increasingly targets modifiable midlife risk states contributing to neurodegenerative vulnerability.While vascular and metabolic factors are established, a substantial proportion of risk remains unexplained.Central sensitization syndromes (CSS)-chronic conditions characterized by neural amplification-are highly prevalent, co-occur with depression and sleep disturbance, and involve neuroimmune and network-level mechanisms implicated in early Alzheimer's disease. ObjectiveTo synthesize epidemiologic evidence linking CSS with incident dementia and evaluate competing causal explanations, including shared vulnerability, reverse causation, and medication-related confounding. MethodsA structured narrative review was conducted of longitudinal cohort and meta-analytic studies assessing incident dementia across CSS-related conditions. ResultsMultiple CSS-including migraine, fibromyalgia, irritable bowel syndrome, restless legs syndrome, and post-traumatic stress disorder-are associated with modest-to-moderate increases in dementia risk.Multisite chronic pain demonstrates dose-response relationships with hippocampal atrophy and incident dementia.However, many