Cognitive impairment in systemic autoimmune and inflammatory diseases: A narrative review focused on ANCA-associated vasculitis, sarcoidosis, Sjögren's syndrome, systemic sclerosis, and Behçet's disease

Cognitive impairment is an increasingly recognized feature of systemic autoimmune and inflammatory diseases, yet remains underdiagnosed and insufficiently studied beyond systemic lupus erythematosus. In this narrative review, we explore the prevalence, clinical profiles, and pathophysiological mechanisms of cognitive dysfunction in five systemic diseases: ANCA-associated vasculitis (AAV), primary Sjögren's syndrome (pSS), systemic sclerosis (SSc), sarcoidosis, and Behçet's disease (BD). We conducted a structured literature search in PubMed and Embase to identify relevant studies published between 1954 and 2024. Reported prevalence varies widely: ∼30 % in AAV, 0–35 % in sarcoidosis, 10–80 % in pSS, 8–65 % in SSc, and 30–100 % in BD. Executive dysfunction and attention deficits predominate. In some cases—particularly in AAV and BD—cognitive decline may reflect direct central nervous system involvement, but many patients report cognitive complaints without overt neurological manifestations or imaging abnormalities. Proposed mechanisms include blood-brain barrier disruption, cytokine-driven neuroinflammation (notably IL-6, TNF-α, IFN-γ, BAFF), autoantibody-mediated synaptic toxicity, and cerebral hypoperfusion linked to small-vessel vasculopathy. Glial activation and neuroimmune dysregulation are recurring findings in animal models and functional imaging studies. White matter lesions and abnormal brain perfusion on MRI or SPECT are frequently observed in asymptomatic patients. Comorbid symptoms such as depression, fatigue, pain, and small fiber neuropathy may exacerbate or mimic cognitive dysfunction. Despite its prevalence and impact on quality of life, cognitive dysfunction is rarely screened, partly due to a lack of standardized tools. Harmonized neurocognitive assessment protocols and longitudinal studies are urgently needed to improve understanding, detection, and management of cognitive impairment, and support its integration into routine care.