F041 When the invisible becomes visible: the cognitive composite score may predict HD severity in prodromal populations at 10-year follow-up

<h3>Background</h3> We generated a Cognitive Composite Score (CCS) using the ENROLL-HD Periodic Data Set (PDS#5). CCS was obtained by a formula combining four cognitive measures (SDMT, FVT, SCN, SWR) for three groups: low, average, and high cognitive performance (LCP, ACP, HCP, respectively). It is potentially predictive of motor severity in the prodromal population. <h3>Aims</h3> Validation of the CCS in a prodromal patient cohort of Italian origin across a 10-year observation period (2014–2024). <h3>Methods</h3> Out of the 80 HD participants who phenoconverted from prodromal to manifest HD, 45 were followed up annually for at least 3 years (3.28 ± 0.77). Clinical assays were completed at the prodromal (T1) and post-phenoconversion HD stages (T2 to T4). We obtained data using the CCS, Total Motor Score (TMS) and Problem Behavioral Assessment Short Form (PBA-s) at each time point. <h3>Results</h3> Correlation analyses confirmed the significant association between lower cognitive performance as measured by CCS and poorer post-phenoconversion motor performance (T2: r = -0.41, p &lt; 0.000; T3: r = -0.45, p &lt; 0.000; T4: r = -0.47, p = 0.001). Prodromal CCS was associated with a significantly higher TMS score in the LCP group than in the ACP and HCP groups at T3 and T4 (ANOVA repeated measures, p &lt; 0.05). We also observed a significant negative correlation between CCS and PBA-s apathy score at T4 (r = -0.40, p = 0.007), with LCP showing higher, time-independent, apathy scores than the ACP and HCP groups (ANOVA repeated measures, p &lt; 0.05). <h3>Conclusions</h3> CCS may potentially be used to predict the severity of clinical manifestations in cohorts of prodromal HD participants – the phase in which HD is still invisible.