Progressive alterations in white matter microstructure across the timecourse of Huntington's disease.

Background: Whole-brain longitudinal diffusion studies are crucial to examine changes in structural connectivity in neurodegeneration. Here, we investigated the longitudinal alterations in white matter (WM) microstructure across the timecourse of Huntington's disease (HD).

Methods: We examined changes in WM microstructure from premanifest to early manifest disease, using data from two cohorts with different disease burden.

Longitudinal Diffusion Tensor Imaging Shows Progressive Changes in White Matter in Huntington's Disease.

Background: Huntington's disease is marked by progressive neuroanatomical changes, assumed to underlie the development of the disease's characteristic symptoms. Previous work has demonstrated longitudinal macrostructural white-matter atrophy, with some evidence of microstructural change focused in the corpus callosum.

Objective: To more accurately characterise longitudinal patterns, we examined white matter microstructural change using Diffusion Tensor Imaging (DTI) data from three timepoints over a 15 month period.

Short-interval observational data to inform clinical trial design in Huntington's disease.

Objectives: To evaluate candidate outcomes for disease-modifying trials in Huntington's disease (HD) over 6-month, 9-month and 15-month intervals, across multiple domains. To present guidelines on rapid efficacy readouts for disease-modifying trials.

Methods: 40 controls and 61 patients with HD, recruited from four EU sites, underwent 3 T MRI and standard clinical and cognitive assessments at baseline, 6 and 15 months.

Inconsistent emotion recognition deficits across stimulus modalities in Huntington׳s disease.

Background: Recognition of negative emotions is impaired in Huntington׳s Disease (HD). It is unclear whether these emotion-specific problems are driven by dissociable cognitive deficits, emotion complexity, test cue difficulty, or visuoperceptual impairments. This study set out to further characterise emotion recognition in HD by comparing patterns of deficits across stimulus modalities; notably including for the first time in HD, the more ecologically and clinically relevant modality of film clips portraying dynamic facial expressions.

Cerebellar abnormalities in Huntington's disease: a role in motor and psychiatric impairment?

The cerebellum has received limited attention in Huntington's disease (HD), despite signs of possible cerebellar dysfunction, including motor incoordination and impaired gait, which are currently attributed to basal ganglia atrophy and disrupted fronto-striatal circuits. This study is the first to investigate a potential contribution of macro- and microstructural cerebellar damage to clinical manifestations of HD. T1- and diffusion-weighted 3T magnetic resonance imaging (MRI) scans were obtained from 12 controls and 22 early-stage HD participants.

Test-Retest Reliability of Diffusion Tensor Imaging in Huntington's Disease.

Diffusion tensor imaging (DTI) has shown microstructural abnormalities in patients with Huntington's Disease (HD) and work is underway to characterise how these abnormalities change with disease progression. Using methods that will be applied in longitudinal research, we sought to establish the reliability of DTI in early HD patients and controls. Test-retest reliability, quantified using the intraclass correlation coefficient (ICC), was assessed using region-of-interest (ROI)-based white matter atlas and voxelwise approaches on repeat scan data from 22 participants (10 early HD, 12 controls).

Longitudinal neuroimaging biomarkers in Huntington's Disease.

Identifying markers able to characterise the progression of Huntington's Disease (HD) is of great importance to the HD research community, as such markers may provide valuable outcome measures in future clinical trials. Neuroimaging measures are obvious candidates because of their clear relevance to the neuropathology of the disease. Many also show improved precision and sensitivity compared with standard functional scales.

Evaluation of multi-modal, multi-site neuroimaging measures in Huntington's disease: Baseline results from the PADDINGTON study.

Background: Macro- and micro-structural neuroimaging measures provide valuable information on the pathophysiology of Huntington's disease (HD) and are proposed as biomarkers. Despite theoretical advantages of microstructural measures in terms of sensitivity to pathology, there is little evidence directly comparing the two.

Methods: 40 controls and 61 early HD subjects underwent 3 T MRI (T1- and diffusion-weighted), as part of the PADDINGTON study.