Introduction: Sarcoidosis has a heterogeneous impact on quality of life (QoL) and cognitive function. Despite their clinical importance, 'brain fog' and cognitive profiles are still poorly understood.
Objectives: Characterise clinical and neurocognitive profiles, evaluate the impact of neurological involvement, gender and disease- burden.
Materials and Methods: 71 patients were enrolled (25.3% NS; 35.2% female; median age 57.7 years). Assessments included: FAS (fatigue), ESS (sleepiness), BDI-II (depression), VAS (pain), SF-36 (QoL) and SDMT (cognitive processing speed). Neurosarcoidosis patients (NS) underwent a comprehensive neuropsychological test panel (TMT, Fluency and Memory tests).
Results: 69% of patients were on active treatment. NS patients had higher rates of biologics use (66.7% vs. 17.0%, p=0.0002). Fatigue was the predominant symptom (prevalence 56.1%), more severe in women (p = 0.0078). QoL was significantly lower than the Italian norm (p < 0.0001), mostly in 'Physical Role' and 'Pain' domains. SDMT analysis revealed a global cognitive deficit, independent of fatigue and depression, suggesting an organic origin of 'brain fog'. A significant gender difference emerged in the NS: men performed significantly worse than women (median 29.5 vs 53.0; p = 0.008). This “female advantage” was confirmed by multiple regression as an effect independent of age. NS patients showed severe deficits were observed in phonemic fluency and cognitive flexibility (TMT-B). K-mean cluster analysis identified three phenotypes: 'Resilient' (57%), 'Algic' (32%), and 'Fatigued/Depressed' (11%). Pain correlated with disease duration (p=0.008), while BDI-II score improved over time (p=0.038) suggesting psychological adaptation.
Conclusions: Cognitive impairment, specifically in processing speed, is a defining feature of sarcoidosis, independently of psychological distress. Although NS triggers severe cognitive decline in men, the overall cohort shows performance below normative levels. These findings emphasize the need for systematic cognitive screening of all patients. Early identification of "brain fog" is essential for the implementation of targeted therapeutic strategies and longitudinal monitoring, particularly in high-risk subgroups (men with NS).