2025. AASLD The Liver Meeting Abstract and Poster: 4479: "THIS IS NOT NORMAL”; UNDERSTANDING COGNITIVE IMPAIRMENT THROUGH QUALITATIVE INTERVIEWS WITH ADULTS WITH PSC TO INFORM MEASURE DEVELOPMENT

Authors: Donna Evon, Kaya Merkler, Laura Mkumba, Lauren Wright, Nicole Lucas, Ricky Safer, Joanne Hatchett, Rachel Gomel, Stephen Rossi, Patrick Smith, Mark Swain, Sasha Deutsch-Link, Bryce Reeve

Abstract:

Background: Understanding cognitive impairment experiences for adults living with PSC is essential for the development of PSC-specific, patient-reported outcome (PRO) measures that accurately reflect their real-world impact. Cognitive impairment (“brain fog”) in PSC is under-recognized yet can be frequent and debilitating, and is differentiated from hepatic encephalopathy.

Methods: Adults were recruited through the PSC Partners Patient Registry and PSC hepatologists in the U.S and screened for a range of PSC-related symptoms. Purposeful sampling was used to select 17 participants for in-depth, individual interviews focused on key symptoms, including cognitive impairment. Interviews were conducted virtually, audio-recorded, transcribed, and analyzed using NVivo software.

Results: Eleven out of 17 participants were interviewed regarding their experience with cognitive impairment. Participants were on average 43 years old (range: 27- 65), 55% male, 27% Black, 64% White, and 55% had inflammatory bowel disease. The Table below provides participants’ illustrative quotes aligned with cognitive domains and life impacts. Severity ranged from mild to debilitating, with a few participants reporting inability to drive, cook independently, work full-time, or engage socially. Participants primarily characterized their cognitive impairments as occurring in the areas of working memory, verbal fluency, sustained attention, and processing speed. Others described a mental “wall” preventing them from absorbing and processing information. Half of participants endorsed experiencing some type of cognitive impairment on a daily basis, while others experienced it “a few days” a week or month. A “domino effect” can occur that begins with cognitive impairment reducing work productivity, which cuts into social time, and in turn, worsens mental health. Cognitive impairment. often accompanied fatigue, but

reportedly can also occur alone. Most participants were able to differentiate PSC-related cognitive impairment from other causes based on association with severe fatigue, improvements with ERCPs and lactulose, and worsening during cholangitis attacks.

Conclusion: PSC cognitive impairment is multi-faceted and impacts daily, work-related, and social activities among symptomatic adults with PSC. These findings will inform the customization of a PSC-specific PROMIS® Cognitive Function measure with strong content validity, enhancing its relevance for future clinical research and treatment evaluation.