Image-HD: Magnetic resonance imaging (MRI) predictors of neuropsychological and motor function in pre-symptomatic and symptomatic Huntington's disease.

Abstract

Background: The role of white matter (WM) degeneration in the motor/cognitive decline in Huntington's disease (HD) is not well understood. Our aim was to use Diffusion Tensor Imaging (DTI) to investigate regions of white matter degeneration in gene-positive participants with (symptomatic) and without (pre-symptomatic) subtle motor symptoms. We also compared the ability of white matter microstructure and striatal volume measures to predict variability in motor and neuropsychological score. Method(s): Sixteen pre-symptomatic (UHDRS mean 0.50), 16 symptomatic (UHDRS mean 18.63) and 17 controls underwent structural T1 and DTI scans (60 directions, b=1200mm2/second). Volumes of the caudate and putamen were obtained. Scores on the UHDRS motor scale, Symbol Digit Modalities Test (SDMT), Stroop word (STROOP), Beck Depression Inventory (BDI) and Smell Identification Test (SIT) were measured. Years to onset (YTO) was estimated as the age of 95% probability of onset given CAG repeat. Result(s): Compared to controls, pre-symptomatic HD participants showed significant (p<0.05) degeneration (reduced FA) in prefrontal and premotor regions of the corpus callosum (CC), as well as in the splenium. Compared to pre-symptomatic gene carriers, symptomatic individuals showed significant degeneration mainly in motor and somatosensory regions of the CC. WM FA significantly (p<0.05) correlated with UHDRS (-.77), SDMT (.80), STROOP (.76), BDI (-.68) and SIT (.72), mainly in the prefrontal/motor CC. YTO did not correlate with FA. UHDRS score correlated significantly (p<0.05) with caudate (-.58) and putamen (-.55) volume, SDMT correlated with putamen (.37) volume, and SIT correlated significantly with caudate (.54) and putamen (.38) volume. Conclusion(s): WM degeneration underlying prefrontal and premotor regions is detectable before motor symptoms are evident. Both WM disconnection and striatal atrophy likely contribute to progressive decline in motor and neuropsychological function in HD.