Long-term Risk of Dementia in Persons With Schizophrenia A Danish Population-Based Cohort Study

IMPORTANCE Although schizophrenia is associated with several age-related disorders and considerable cognitive impairment, it remains unclear whether the risk of dementia is higher among persons with schizophrenia compared with those without schizophrenia. OBJECTIVE To determine the risk of dementia among persons with schizophrenia compared with those without schizophrenia in a large nationwide cohort study with up to 18 years of follow-up, taking age and established risk factors for dementia into account. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study of more than 2.8 million persons aged 50 years or older used individual data from 6 nationwide registers in Denmark. A total of 20 683 individuals had schizophrenia. Follow-up started on January 1, 1995, and ended on January 1, 2013. Analysis was conducted from January 1, 2015, to April 30, 2015. MAIN OUTCOMES AND MEASURES Incidence rate ratios (IRRs) and cumulative incidence proportions (CIPs) of dementia for persons with schizophrenia compared with persons without schizophrenia. RESULTS During 18 years of follow-up, 136 012 individuals, including 944 individuals with a history of schizophrenia, developed dementia. Schizophrenia was associated with a more than 2-fold higher risk of all-cause dementia (IRR, 2.13; 95% CI, 2.00-2.27) after adjusting for age, sex, and calendar period. The estimates (reported as IRR; 95% CI) did not change substantially when adjusting for medical comorbidities, such as cardiovascular diseases and diabetes mellitus (2.01; 1.89-2.15) but decreased slightly when adjusting for substance abuse (1.71; 1.60-1.82). The association between schizophrenia and dementia risk was stable when evaluated in subgroups characterized by demographics and comorbidities, although the IRR was higher among individuals younger than 65 years (3.77; 3.29-4.33), men (2.38; 2.13-2.66), individuals living with a partner (3.16; 2.71-3.69), those without cerebrovascular disease (2.23; 2.08-2.39), and those without substance abuse (1.96; 1.82-2.11). The CIPs (95% CIs) of developing dementia by the age of 65 years were 1.8%(1.5%-2.2%) for persons with schizophrenia and 0.6%(0.6%-0.7%) for persons without schizophrenia. The respective CIPs for persons with and without schizophrenia were 7.4%(6.8%-8.1%) and 5.8% (5.8%-5.9%) by the age of 80 years. CONCLUSIONS AND RELEVANCE Individuals with schizophrenia, especially those younger than 65 years, had a markedly increased relative risk of dementia that could not be explained by established dementia risk factors.