Psychiatry Research · Feb 28, 2026

Role of depression and anxiety in the treatment modalities and age-stratified dementia risk in patients with schizophrenia, a real-world nationwide cohort study

By Li YW, Yeh TC, Chien WC et al.

BACKGROUND: Schizophrenia is associated with elevated dementia risk, yet large-scale epidemiological evidence from Asian populations remains scarce. This study aimed to quantify dementia incidence and identify its key predictors, with particular attention to psychiatric comorbidities and antipsychotic treatment modalities, in a nationwide cohort of patients with schizophrenia in Taiwan. METHODS: Using Taiwan's National Health Insurance Research Database (NHIRD), we conducted a nationwide retrospective cohort study encompassing 8480 patients with schizophrenia followed from 2000 to 2015 (mean follow-up: 9.5 years). Dementia incidence was compared between patients receiving long-acting injectable (LAI) and oral antipsychotics using Fine and Gray competing risk analysis. A 5-year washout period was incorporated to mitigate potential reverse causality bias. RESULTS: The cumulative dementia prevalence was 12.98% over the study period. Advanced age emerged as the primary risk factor. Comorbid anxiety (adjusted hazard ratio [aHR] = 2.77) and depression (aHR = 2.42) were independently associated with significantly elevated dementia risk, findings that remained robust after accounting for potential prodromal confounding. No statistically significant difference in dementia incidence was observed between the LAI and oral antipsychotic groups. CONCLUSIONS: Dementia risk among older patients with schizophrenia is substantially amplified in the presence of psychiatric comorbidities. The comparable cognitive trajectories observed across antipsychotic treatment modalities suggest that the underlying neuroprogressive pathology of schizophrenia may attenuate the anticipated adherence-related benefits of LAIs. These findings underscore the clinical imperative for heightened vigilance and support the integration of structured dementia screening into routine care for this vulnerable population.

doi.org/10.1016/j.psychres.2026.117061PubMed 41849924Populations