Cognitive dysfunction and associated neuroimaging biomarkers in antiphospholipid syndrome: a systematic review

OBJECTIVES: Cognitive dysfunction is common in patients with aPL (including primary APS or APS associated with SLE). Neuroimaging biomarkers may contribute to our understanding of mechanisms of cognitive dysfunction in these cohorts. This review aimed to investigate: (i) the prevalence of cognitive dysfunction in studies including neuroimaging biomarkers; and (ii) associations between cognition and neuroimaging biomarkers in patients with APS/aPL. METHODS: We conducted a systematic search of electronic databases PubMed, Science Direct, Scopus and PsycINFO, and included studies with descriptions of neuroimaging findings, cognitive dysfunction or both, in patients with aPL positivity (LA, IgG and IgM aCL and anti-β2 glycoprotein-I antibodies). RESULTS: Of 120 search results we included 20 eligible studies (6 APS, 4 SLE with APS/aPL and 10 NPSLE). We identified a medium risk of bias in 6/11 (54%) of cohort studies and 44% of case–control studies, as well as marked heterogeneity in cognitive assessment batteries, APS and aPL definitions, and neuroimaging modalities and protocols. The prevalence of cognitive dysfunction ranged between 11 and 60.5%. Structural MRI was the most common imaging modality, reporting cognitive dysfunction to be associated with white matter hyperintensities, ischaemic lesions and cortical atrophy (four with cerebral atrophy, two with white matter hyperintensities and two with cerebral infarcts). CONCLUSION: Our findings confirm that cognitive impairment is commonly found in patients with aPL (including APS, SLE and NPSLE). The risk of bias, and heterogeneity in the cognitive and neuroimaging biomarkers reported does not allow for definitive conclusions.