Cognitive Impairment and Its Clinical and Neuroimaging Correlates in Fabry Disease: A Single-Center Retrospective Cross-Sectional Study

Background To characterize the prevalence and profile of cognitive impairment in Fabry disease (FD) and examine its clinical, neuroimaging, and biomarker correlates. Methods In this single-center retrospective cross-sectional study, we included 57 patients with FD who underwent standardized cognitive assessment; primary analyses were restricted to 50 adults. Clinical characteristics, neuroimaging (ARWML and Fazekas scores), and biomarkers (α-Gal A activity and plasma Lyso-Gb3) were evaluated in relation to cognitive impairment using age-adjusted and multivariable analyses. Results Cognitive impairment was present in 19 of 50 adults (38.0%), predominantly involving delayed recall, visuospatial/executive function, attention, and language. Subjective memory decline was strongly associated with objective cognitive impairment (82.4% vs. 42.9%; OR = 6.22, 95% CI 1.45–26.64). Cognitively impaired adults were older (46.7 vs. 37.3 years, P = 0.005), had longer disease duration (32.8 vs. 22.9 years, P = 0.033), and had higher Mainz Severity Score Index (MSSI) scores (21.0 vs. 10.0, P = 0.008). Greater white matter lesion burden was associated with poorer cognitive performance after age adjustment (r = − 0.40 to − 0.74; all q < 0.05), whereas α-galactosidase A activity and Lyso-Gb3 levels were not (all q = 0.83). Higher MSSI scores remained independently associated with cognitive impairment (OR = 1.08 per point, 95% CI 1.01–1.16). Conclusions Cognitive impairment was common in adults with FD, predominantly involving memory and executive-attentional domains. Systemic disease severity and white matter lesion burden were associated with cognitive impairment and poorer cognitive performance, whereas the measured biomarkers were not. Subjective memory complaints may provide a practical indication for formal cognitive assessment.