F095 Total functioning capacity scale in Huntington’s Disease: natural course over time

<h3>Background and Objectives</h3> The Total Functioning Capacity (TFC) assessment has been widely used in Huntington’s disease (HD) research and clinical trials for the past 18 years. It aims to function as a measure of disease stage and disease progression. <h3>Aims</h3> This study investigates the natural course of function in HD of those who experienced a change in TFC-score in relation to age and CAG-repeat length and explores TFC’s clinical strengths and weaknesses in longitudinal studies. <h3>Methods</h3> Using the Enroll-HD platform’s clinical dataset version 5, including Registry-3, with data from 21,079 participants, we focused on 16,083 individuals with an expanded CAG repeat. Our final analysis included 15,527 patients and 52,457 visits with TFC-scores ranging from 0 to 13. <h3>Results</h3> Alluvial charts reveal that most individuals maintain maximum functional capacity over time. Changes in the TFC scores, typically indicate declining functional capacity, as observed in 2224 out of 3505 individuals (64%), but 661 individuals (18%) show improvement within a year. Age-related changes follow a specific sequence: occupation, household chores/finances, daily living, and care. A longer CAG-repeat length correlates with earlier functional decline, and certain geographic regions exhibit slightly earlier losses in one functional domain. The reduced penetrance CAG-repeat group differs in trajectories from full penetrance HD participants. <h3>Discussion</h3> When we focus on those who experienced a change in TFC-score, the number of HD patients with regained functional capacity is substantial, even considering interrater variability, which may influence outcome assessments in clinical trials. The TFC effectively reflects changes in functional domains as intended. Analysis of the reduced penetrance group suggests potential selection biases in seeking medical attention earlier and for reasons unrelated to HD.