F044 Determining clinically meaningful change on cognitive measures used in clinical trials for Huntington’s disease using function as an anchor

<h3>Background</h3> Cognitive measures in Huntington’s disease (HD) play an important role in monitoring disease progression. Measures of functional capacity are often used to determine meaningful change over time and may serve as appropriate anchors to determine the minimally clinically important difference (MCID) on measures of cognition. We compare results to previous research that used the Physical Component of the 12-item short form health survey (SF-12) (Hamilton et al., 2023). <h3>Aims</h3> We aimed to estimate the MCID for cognitive measures commonly used in clinical research, including the Symbol Digit Modality Test (SDMT), Trail Making Test (TMT), Verbal Fluency Test, Stroop Interference Test, and the Mini Mental State Examination (MMSE) using functional capacity measures as anchors. <h3>Methods/Techniques</h3> We analysed data from 12,168 participants from the Enroll-HD study with Stage 2 and Stage 3 HD using the HD Integrated Staging System (HD-ISS). We estimated MCID scores using linear mixed effects regression at 12 months, 24 months, and 36 months. The Unified Huntington’s Disease Rating Scale (UHDRS) Total Functional Capacity (TFC) scale, the UHDRS Functional Assessment Scale (FAS), and the Work Productivity and Activity Impairment-Specific Health Problem Questionnaire were used as anchors. <h3>Results/Outcomes</h3> MCID estimates for cognitive measures increased from HD-ISS Stage 2 to Stage 3 and as timeframes increased. <h3>Conclusions</h3> Consistent with previous research, MCID estimates differ between disease stages and over different timeframes. Understanding the MCID on measures of cognition using function as anchors improves the interpretability of how change on such measures translates to everyday life.