The pathogenesis of Alzheimer’s disease (AD) remains uncertain. Neuroinflammation and autoimmunity are leading hypotheses supported by links between systemic inflammation and dementia. Yet, evidence from post-mortem studies and longitudinal studies on AINDs has been inconsistent. This study provides an adjusted pooled estimate of dementia risk across individual and collective AINDs.

This PRISMA-compliant systematic review used a MeSH-enhanced, neurologist- and librarian-reviewed search across PubMed, Scopus, Web of Science, and grey literature to pool adjusted risk ratios (aRR) of ICD-coded dementia from cohort/case-control studies. Adjusted odds and hazard ratios were converted to risk ratios when possible. Random-effects models in R (v4.4.1) generated weighted pooled estimates. PROSPERO registration (CRD420251031380) was attempted prospectively.

From 23,129 records, 23 studies were included (3,847,830 patients with immune-mediated conditions and 26,322,203 controls). AINCs were associated with a higher risk of all-cause dementia(ACD) (aRR = 1.45; 95% CI 1.26-1.68; I² = 96.2%). Egger’s test indicated publication bias (p = 0.03). After excluding an outlier, AINC increased AD risk (aRR = 1.18; 95% CI 1.04-1.33) but not vascular dementia (VD) (aRR = 1.18; 95% CI 0.99-1.38). Multiple sclerosis (MS) showed a significantly elevated risk of ACD (aRR = 1.65; 95% CI 1.33-2.03), AD (aRR = 1.33; 95% CI 1.07-2.65), and VD (aRR = 1.18; 95% CI 1.05-1.32), with minimal heterogeneity (I²<50%). Females with MS showed a higher ACD risk (aRR 1.72 vs. 1.55 in males). Neuromyelitis optica was associated with higher risks of AD, VD, and ACD (aRR = 1.97, 3.20, and 2.16, respectively). Myasthenia gravis, Guillain–Barré syndrome, and dermatomyositis/myositis showed non-significant trends toward increased dementia risk (p > 0.05).

These findings underscore the role of immune dysregulation in dementia pathogenesis. Further research should explore whether controlling AINDs can reduce dementia risk.