The PREDICT-HD study seeks to identify clinical and biological markers of Huntington’s disease in premanifest individuals who have undergone predictive genetic testing.

We compared baseline motor data between gene-expansion carriers (cases) and non gene-expansion carriers (controls) using T-tests and Chi-Square. Cases were categorized as near, mid or far from diagnosis using a CAG-based formula. Striatal volumes were calculated using volumetric MRI measurements. Multiple linear regression associated total motor score, motor domains and individual motor items with estimated diagnosis and striatal volumes.

Elevated total motor scores at baseline were associated with higher genetic probability of disease diagnosis in the near future (partial R2 0.14, p<0.0001) and smaller striatal volumes (partial R2 0.15, p<0.0001). Nearly all motor domain scores showed greater abnormality with increasing proximity to diagnosis, although bradykinesia and chorea were most highly associated with diagnostic immediacy. Among individual motor items, worse scores on finger tapping, tandem gait, Luria, saccade initiation, and chorea show unique association with diagnosis probability.

Even in this premanifest population subtle motor abnormalities were associated with a higher probability of disease diagnosis and smaller striatal volumes. Longitudinal assessment will help inform whether motor items will be useful measures in preventive clinical trials.