Platform Presentation—Longitudinal Structural MRI Data from PREDICT-HD: Striatal and Cortical Changes in Pre-Clinical HD

Background PREDICT-HD is a large multi-site study of individuals with the HD gene expansion who have not yet been diagnosed with the disorder (pre-HD), as well as a smaller group of gene-negative control subjects. Subjects have been followed-up yearly with extensive neuropsychological testing, clinical evaluation, and psychiatric assessment, and every two years with MRI. Methods The sample used for the current analysis included 215 pre-HD participants, 35 individuals newly diagnosed with HD, and 47 age- and sex-matched control subjects. At least two scans, obtained with an interscan interval of 2 years, were analyzed for each subject. Measurements included volumes of caudate, putamen, thalamus, gray, and white matter. Pre-HD subjects were divided into groups based on their estimated proximity to onset (Far, >15 years; Mid, 9-15 years; and Near, Results Longitudinal change in striatal volume was greater for the Mid, Near, and Diagnosed subjects than for the Control or Far subjects. There was no significant difference between the Far and Control subjects for amount of longitudinal change, and no significant differences among the Mid, Near, and Diagnosed groups. Results for caudate and putamen were the same as those for total striatal volume change. For thalamus, Near and Diagnosed subjects had greater longitudinal change than the other three groups. Effect sizes were calculated, as well as power analyses to demonstrate the number of subjects per treatment group that would be necessary for trials conducted at each preclinical stage. Data for total gray and white volume will also be presented. Conclusions Disease-related longitudinal change in striatal volume is observable over a two-year period in individuals who are within 15 years of estimated disease onset, and rate of change is fairly consistent over time once it begins. Observable longitudinal change for the thalamus begins later in the disease process.