F061 Risk factors associated with cognitive/psychiatric/behavioural phenotypes in Huntington’s disease

<h3>Background</h3> Huntington’s disease (HD) patients show increased rates of behavioural, cognitive and psychiatric phenotypes compared to the general population. Some of these are associated with disease progression. <h3>Aims</h3> Use Enroll-HD to systematically test associations of baseline behavioural, cognitive and psychiatric phenotypes with HD-ISS disease stage, and also with age, sex, CAG length, BMI, alcohol, tobacco, caffeine and drug use. To perform data reduction on the phenotypes (utilising their correlations) to derive composite scores, and test these for association with the risk factors. <h3>Methods</h3> Multivariable linear or logistic regression was performed using each of the 46 phenotypes on all risk factors simultaneously. Principal component analysis was used to identify linear combinations of phenotypes that best explain the variation. <h3>Results</h3> Most phenotypes showed significant deterioration in stage 3. Anxiety and depression were more common in females, while violence/aggression and alcohol abuse were more common in males. Cognitive phenotypes worsen with increasing age, while irritability and depression decrease. Drug and tobacco use were associated with worsening in several psychiatric variables. Two principal components were observed: the first accounts for ~40% of the phenotypic variance and comprises cognitive variables, along with TMS, TFC and PBA apathy. The second accounts for ~12% of variance and comprises PBA/HADS-SIS depression/anxiety/irritation. Both show a steady change across disease stages. <h3>Conclusions</h3> Individual phenotypes show variable patterns of change across disease stages. However, we identified two principal components that both show a significant and steady change across disease stage. These may be useful measures of disease progression in genetic studies.