Modeling the relationship between function, cognition, and motor ability in Huntington's Disease

<b>Background</b>In Huntington’s Disease, motor and cognitive impairment both contribute to functional impairment, where a person’s ability to work and care for themselves becomes limited.<b>Objectives</b>The author sought to predict a subject’s functional impairment given the subject’s measured cognition and motor impairment.<b>Methods</b>Ordinal models were developed and fit to baseline data from the global observational study ENROLL-HD (N = 9,072). The Symbol Digits Modality Test (SDMT) was used to quantify cognition and, the Total Motor Score (TMS) was used to quantify motor ability. The models predicted the Total Functional Capacity (TFC) and Independence Score (IS) from the SDMT and TMS.<b>Results</b>Both SDMT and TMS were statistically significant predictors of function. The predicted function showed strong correlation with the observations (Pearson r of 0.82 for TFC and 0.84 for IS). The models were applied to predict functional improvements resulting from hypothetical treatments that improved SDMT or TMS. For example, it was projected that a 5 point improvement in SDMT would cause a mean improvement of 0.33 in TFC.<b>Conclusions</b>The models have implications for drug development, where rapidly acting symptomatic treatments may show improved cognitive or motor performance, but functional effects may be delayed or require large sample sizes to detect. Predicting functional effects with these models may support sample size calculations for future trials.<br>