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

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.