Cerebral amyloid angiopathy-related inflammation (CAA-ri): an updated systematic review and meta-analysis

Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare subtype of CAA, and it is correlated with pathological evidence of inflammation against amyloid-β in the walls of blood vessels and the surrounding tissue. Limited data exist on the prevalence of clinical, neuroimaging, and genetic characteristics in CAA-ri.

A systematic review and meta-analysis pooled data from published studies on CAA-ri. Random-effects models were used to calculate pooled prevalence rates, and heterogeneity was assessed using I² and τ² statistics.

We identified 4 prospective and 22 retrospective cohort studies comprising 553 patients with CAA-ri (mean age, 70.9 years; women, 51.29%). Prevalence rates were: cognitive decline at presentation 66% ([95% CI 50-80%]; I² = 69.6%, τ² = 1.92, p < 0.001), focal neurological deficits 53% ([95% CI 43-63%]; I² = 47.4%, τ² = 0.33, p = 0.009), seizures 33% ([95% CI 26-41%]; I² = 47.4%, τ² = 0.33, p = 0.009), headache 29% ([95% CI 23-35%]; I² = 34.3%, τ² = 0.13, p = 0.08), lobar cerebral microbleeds 96% ([95% CI 87-99%]; I² = 49.3%, τ² = 3.54, p = 0.008), gadolinium enhancing lesions 48% ([95% CI 35-61%]; I² = 68.6%, τ² = 0.79, p < 0.001), cortical superficial siderosis 42% ([95% CI 33-53%]; I² = 53.1%, τ² = 0.47, p = 0.004), and lobar macro hemorrhage 40% ([95% CI 16-71%]; I2 = 46.8%, τ2 = 2.51, p = 0.08), and ischaemic infarcts 15% ([95% CI 10-20%]; I² = 23.7%, τ² = 0, p = 0.26 = 23.7%, τ² = 0, p = 0.26). The prevalence rate of the APOE (Apolipoprotein E) ε4/ε4 genotype was 42% ([95% CI 28-58%]; I² = 77.8%, τ² = 0.68, p < 0.001) while ε2/+ allele was 23% ([95% CI 12-39%]; I² = 84.5%, τ² = 0.84, p < 0.001. Finally, steroid therapy was the most commonly adopted treatment approach with a pooled prevalence of 79% (95% CI 64-88%; I² = 76.8%, τ² = 1.52, p < 0.001). Leave-one-out sensitivity analyses confirmed the robustness of pooled estimates across all outcomes. Subgroup analysis revealed a significantly higher prevalence of seizures in biopsy-confirmed cohorts compared to clinically diagnosed cases. Meta-regression identified significant associations between mean patient age and focal neurological deficits (p=0.037), headache (p=0.002), and lobar cerebral microbleeds (p=0.048).

Cognitive decline and focal neurological deficits were the most common clinical features, while lobar cerebral microbleeds were the predominant neuroimaging finding. Forty-two percent of patients carried the homozygous APOE ε4/ε4 genotype, seventy-nine percent underwent steroid therapy, and favorable outcomes were observed in seventy-five percent of cases.