Age-stratified associations between severe mental illness, dementia, and ischemic stroke: findings from the PADRIS-PRESTO cohort

Abstract

People with severe mental illnesses (SMIs), including schizophrenia spectrum disorders (SSD), major depressive disorder (MDD), and bipolar disorder (BD), experience elevated rates of physical comorbidity and premature mortality. Dementia and ischemic stroke contribute substantially to this burden, yet age-specific patterns of these associations remain poorly characterized. To bridge this gap, we conducted a population-based cross-sectional study using the PADRIS-PRESTO cohort, integrating primary and specialized care records from the Catalan public health system (Spain). Adults with a lifetime SMI diagnosis were compared with controls without any psychiatric condition. Weighted age-stratified prevalence was calculated and logistic regression models estimated age-specific odds ratios (ORs) with 95% confidence intervals (CIs), adjusting for socioeconomic status and medical comorbidity burden. Among 694,086 participants, 176,870 had an SMI diagnosis. Dementia prevalence was 3.49% (range, 0.33% at ages 20-29 to 39.51% at 90-99 years) in SMIs and 0.36% (0.02%-17.7%) in controls. Ischemic stroke prevalence was 5.3% (0.22%-16.4%) in SMIs and 2.75% (0.08%-14.67%) in controls. The ORs between SMI and dementia were significant across all age groups, with the strongest association observed at younger ages (OR = 23.21, 95% CIs = 13.74-39.19 at 30-39 years). Elevated ORs for stroke persisted up to 70-79 years, peaking at 40-49 years (OR = 2.99, 95% CIs = 2.63-3.41). Patterns were consistent across SMI subtypes. These findings highlight the need for earlier and more systematic neurological and cardiometabolic screening and management within psychiatric care and support policies that recognize SMIs as risk factors for vascular diseases and dementia.