Associations of chronic inflammatory diseases with brain health: a prospective cohort study

Background Chronic inflammatory diseases (CIDs) are common and characterized by persistent systemic inflammation, but their broader impact on brain health remains poorly understood. We aimed to examine the associations of 14 common CIDs with brain health in the UK Biobank participants. Methods We conducted a prospective cohort study using data from 502,411 UK Biobank participants aged 40–69 years at baseline (2006–2010), with follow-up through linked hospital, primary care, and mortality records. Fourteen common CIDs were identified. Neurological outcomes included stroke, dementia, Parkinson’s disease, cognitive performance, and magnetic resonance imaging derived phenotypes. Associations were assessed using Cox proportional hazards models and logistic regressions. Mediation analyses were conducted to evaluate the potential role of systemic inflammatory markers in these associations. Results Among 502,411 participants (56.5 ± 8.1 years; 54.4% women), 44.4% had at least one CID. Over a mean follow-up of 8.9 years, CID presence was associated with increased risks of stroke (hazard ratio [HR] 1.46; 95% confidence interval, 1.43–1.50), dementia (HR 1.43, 1.36–1.50), and Parkinson’s disease (HR 1.34, 1.26–1.43), with stronger associations among individuals younger than 65 years. Type 1 diabetes conferred the highest risk, with approximately threefold increased risks of stroke and dementia. Up to 24% of observed associations were mediated by neutrophil-based inflammatory indices. In contrast, allergic rhinitis was linked to reduced neurological risk and better cognition. Neuroimaging analysis revealed widespread white matter microstructural disruption across CIDs. Conclusions Our findings highlight the broader neurological impact of CIDs and reveal substantial heterogeneity across CID subtypes. Early identification and management of CIDs may help mitigate long-term risks to brain health.