Increased risk of dementia in patients with Schizophrenia: A population-based cohort study in Taiwan

Background: The extent to which schizophrenia is associated with the risk of all-cause dementia is controversial. This study investigated the risk of dementia by type in patients with schizophrenia. Methods: Data were collected from the Taiwanese National Health Insurance Database 2005 and analyzed using multivariate Cox proportional hazard regression models to determine the effect of schizophrenia on the dementia risk after adjusting for demographic characteristics, comorbidities, and medications. Fine and Gray's competing risk analysis was used to determine the risk of dementia, as death can act as a competing risk factor for dementia. Results: We assessed 6040 schizophrenia patients and 24,160 propensity scale-matched control patients. Schizophrenia patients exhibited a 1.80-fold risk of dementia compared to controls (adjusted hazard ratio [aHR] = 1.80, 95% confidence interval [CI] = 1.36 ∼ 2.21, p < 0.001) after adjusting for covariates. Cardiovascular disease (aHR = 5.26; 95% CI = 4.50 ∼ 6.72; p < 0.001), hypertension (aHR = 1.83; 95% CI = 1.77 ∼ 2.04; p = 0.002), traumatic head injury (aHR = 1.35; 95% CI = 1.24 ∼ 1.78; p < 0.001), chronic lung diseases (aHR = 1.64; 95% CI = 1.13 ∼ 2.56; p < 0.001), alcohol-related disorders (aHR = 3.67; 95% CI = 2.68 ∼ 4.92; p < 0.001), and Parkinson's disease (aHR = 1.72; 95% CI = 1.25 ∼ 2.40; p < 0.001) were significantly associated with dementia risk. Notably, first-generation antipsychotics (aHR = 0.80; 95% CI = 0.56 ∼ 0.95; p = 0.044) and second-generation antipsychotics (aHR = 0.24; 95% CI = 0.11 ∼ 0.60; p < 0.001) were associated with a lower dementia risk. Sensitivity tests yielded consistent findings after excluding the first year and first 3 years of observation. Patients with schizophrenia had the highest risk of developing Alzheimer's [dementia/disease?] among dementia subtypes (aHR = 2.10; 95% CI = 1.88 ∼ 3.86; p < 0.001), followed by vascular dementia (aHR = 1.67; 95% CI = 1.27 ∼ 2.12; p < 0.001) and unspecified dementia (aHR = 1.30; 95% CI = 1.04 ∼ 2.01; p < 0.001). Conclusions: Schizophrenia was significantly associated with the risk of all-cause dementia. Data are scarce on the mechanisms through which antipsychotic agents protect persons with schizophrenia from developing dementia. Further research is recommended to elucidate the neurobiological mechanisms underlying the association between schizophrenia and dementia, and whether antipsychotics protect against the development of dementia in schizophrenia.