Neurocognitive Dysfunction in Fibrosing Interstitial Lung Diseases: A Multidimensional Analysis of Pulmonary,...

Background and Objectives: Fibrosing interstitial lung diseases (ILDs) may predispose to neurocognitive impairment through chronic hypoxemia and systemic inflammation, yet data integrating pulmonary physiology, disease severity, and cognition are limited. We aimed to compare global cognitive performance between adults with fibrosing ILD and contemporaneous non-ILD clinic comparators, explore differences across ILD subtypes, and identify physiologic and clinical predictors of low MMSE scores. Materials and Methods: In this single-center cross-sectional study, 45 adults with fibrosing ILD and 32 non-ILD participants from university-affiliated pulmonology clinics completed the Mini-Mental State Examination (MMSE) and standardized lung function testing (including diffusing capacity, DLCO%). Comorbidity (Charlson index), inflammatory markers (C-reactive protein), and GAP (Gender-Age-Physiology) severity were recorded. Associations with MMSE and MMSE < 24 were examined using correlations and multivariable logistic regression. Results: Mean MMSE was lower in ILD than in non-ILD participants (23.9 ± 3.6 vs. 26.8 ± 2.8; p < 0.001), and MMSE < 24 occurred in 33.3% versus 12.5%, respectively. Within ILD, the usual interstitial pneumonia (UIP) pattern showed the lowest MMSE scores. DLCO% and total lung capacity correlated positively with MMSE (r = 0.44 and r = 0.34, respectively). In multivariable models, ILD diagnosis remained associated with MMSE < 24 (odds ratio [OR] 2.72, 95% CI 1.14-6.48), and each 10-percentage-point decrement in DLCO% increased the odds of MMSE < 24 (OR 1.42, 95% CI 1.11-1.92). GAP ≥ 4 was also associated with impaired cognition (OR 2.91, 95% CI 1.13-7.57). Conclusions: Fibrosing ILD, particularly with reduced diffusing capacity and higher GAP stage, is associated with lower MMSE scores and a higher frequency of values below a conventional impairment threshold. Prospective studies incorporating comprehensive neuropsychological testing are needed to determine whether and how neurocognitive assessment should be integrated into routine ILD care.