A brief acceptance and commitment therapy intervention for individuals at risk of neurodegenerative disease: A translational study in inherited prion disease.

Living at risk of a neurodegenerative condition such as inherited prion disease (IPD) is associated with substantial psychological burden, yet evidence-based supportive interventions are lacking. This unmet need is likely to grow as advances in biomarkers and predictive testing lead to increasing identification of individuals in pre-symptomatic stages of neurodegenerative disease. Acceptance and Commitment Therapy (ACT), a transdiagnostic intervention targeting psychological flexibility, has shown promise in chronic health contexts but has not been evaluated in individuals at genetic risk. Inherited prion disease was used as a model population to examine acceptability, feasibility and preliminary therapeutic effects in a rare neurogenetic context. The intervention comprised a single 5-h, face-to-face group workshop followed by an individual booster session. Prespecified feasibility and acceptability criteria were assessed alongside secondary psychological outcomes at baseline, 1 month, and 3 months post-intervention, complemented by semi-structured qualitative interviews. Twenty-three participants completed the intervention. All predefined feasibility criteria were met, including recruitment (58%), intervention completion (80%), retention at 3 months (79%), and low missing data (10%). Acceptability was high, with all participants reporting the intervention as useful and appropriate. Quantitative analyses demonstrated improvements in psychological quality of life and behavioural awareness at 3 months, with larger effects observed in participants with elevated baseline depressive symptoms. Qualitative findings highlighted the importance of peer connection, experiential learning, and practical strategies for managing uncertainty. These findings provide support for a scalable psychological intervention that may address cost and time barriers and represent an important component of future neurotherapeutic care.