Autoimmune Neurological Disorders and the Risk of Alzheimer’s, Vascular, and Other Dementias: A Comprehensive Systematic Review and Meta-analysis
Mohamed I. Mohamed1, Rana Sameh1, Dana Farghaly2, Basmalla Ashraf1, Bishoy Kamel1, Nadeen Hossam Mahmoud1, Nasser A. Abdelall3, Mona AF Nada4
1Alexandria University, Faculty of Medicine, Alexandria, Egypt, 2Alexandria University, Joint Manchester Program, Faculty of Medicine, Alexandria, Egypt, 3Department of Neurology, Louisiana State University School of Medicine, New Orleans, LA, 4Department of Neurology, Cairo University, Faculty of Medicine, Giza, Egypt
Objective:
To provide an up-to-date quantitative synthesis of dementia risk in individuals with autoimmune neurological conditions (AINDs).
Background:

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.


Design/Methods:

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.


Results:

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).




Conclusions:

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

10.1212/WNL.0000000000215722
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.