Highlight
1. Dementia develops 4- to 20-fold more frequently in individuals with severe, treatment-resistant schizophrenia than in the general population.
2. The pattern of cognitive impairment in severe schizophrenia dementia differs from Alzheimer disease (AD), frontotemporal dementia (FTD), and Lewy body dementia (LBD), resembling an intensified form of schizophrenia-related cognitive deficits.
3. Common genetic risk factors for dementia, including APOE4 and known Mendelian mutations, are significantly less prevalent or absent in this cohort.
4. Cognitive impairment is not explained by premorbid intellectual disability, pharmacotherapy, cardiometabolic risks, or institutionalization effects.
