In intermediate analyses, we first identified regions that showed significant cortical thinning and striatal volume loss in a large sample of prHD individuals relative to a gene-negative control group. These regions were then used as predictors of performance on each cognitive measure in the prHD group. As brain regions interact with each other to fulfill a cognitive

function, we hypothesized that performance in each of the domains would be correlated with different Inhibitors,research,lifescience,medical regional patterns of corticostriatal morphometry. The random forest method was used to test the hypothesis, as it is well suited for modeling these find more complicated relationships. Material and Methods Subjects Study participants included 325 prHD individuals and 119 gene-negative controls with a family history of HD. Data for the study were collected at 31 sites in the United States, Canada, Australia, Germany, Inhibitors,research,lifescience,medical Spain, and the United Kingdom from 2002 to 2008 from individuals enrolled in PREDICT-HD (Paulsen et al. 2006, 2008). Consent was obtained according Inhibitors,research,lifescience,medical to the Declaration of Helsinki. The protocol was approved by the institutional review boards at the University of Iowa and each participating site. Participants were 18 years of age or older, had a family history of HD, and completed independent

genetic Inhibitors,research,lifescience,medical testing for the HD CAG expansion prior to entry into PREDICT-HD. Confirmatory DNA testing was conducted on blood drawn at the baseline PREDICT visit using a polymerase chain reaction method to determine CAG-repeat length (Warner et al. 1993). PrHD participants had the expansion (≥38 CAG repeats) and gene-negative controls did not (<36 CAG repeats) (​(1).1). A certified examiner performed the Unified Huntington's

Disease Rating Scale (UHDRS) motor examination on all participants. The UHDRS motor scale contains 31 items that assess chorea, bradykinesia, rigidity, dystonia, and oculomotor function. Ratings for each item range from 0 (normal) to 4 (motor abnormalities, Inhibitors,research,lifescience,medical impairment) and are summed for a total motor score (Table 1). Examiners also rated their level Oxalosuccinic acid of confidence that observed motor signs were an unequivocal manifestation of HD. Individuals with a diagnostic confidence rating of 4 (≥99% confidence that motor symptoms were unequivocal signs of HD) at the time of testing were excluded. Individuals were excluded from participation in PREDICT-HD if they evidenced unstable medical or psychiatric conditions, reported substance abuse within the past year, had a history of learning disability or intellectual disability requiring special education classes, a history of other central nervous system disease (e.g., seizures, traumatic brain injury), or if they had a pacemaker or metallic implants.