Association of immune-mediated diseases with the risk of dementia and brain structure in UK Biobank participants

Abstract Background Immunity and inflammation may be essential to the pathogenesis of dementia. However, the association of immune-mediated diseases with the risk of incident dementia has not been well characterised. Objectives We aimed to investigate the prospective association of 27 immune-mediated diseases and incident dementia risk and to explore the underlying mechanisms driven by brain structures. Methods We included 487 459 UK Biobank participants aged 37–73 years without dementia at enrolment. Immune-mediated diseases and dementia cases were ascertained according to the International Classification of Diseases codes. Time-varying Cox proportional hazards regression and general linear regression models were used to examine the association of immune-mediated disease with incident dementia risk and brain morphometric measures, respectively. Results Over a median follow-up of 12.3 years, 1654 cases of incident dementia were documented in 86 243 patients with immune-mediated diseases. Overall, immune-mediated diseases were associated with a higher all-cause dementia risk (hazard ratio [HR], 1.24; 95% confidence interval, 1.17–1.32). Five out of 27 immune-mediated diseases were associated with an increased risk of dementia individually. Comorbidity of multiple immune-mediated diseases further increased the risk. Moreover, the immune-mediated disease was associated with smaller total surface areas of both left (β, −286.51; SE, 102.58; P = .014) and right hemispheres (β, −298.56; SE, 103.96; P = .016), greater white matter hyperintensities volume (β, 1.02; SE, 0.13; P < .001) and less healthy white matter microstructures. Conclusions Immune-mediated diseases were associated with an increased risk of incident dementia, and the association of those diseases with brain structural abnormalities might provide clues to the underlying mechanisms.