Apathy and atrophy of subcortical brain structures in Huntington's disease: A two-year follow-up study.

Background: Huntington's disease (HD) is characterized by motor and behavioral symptoms, and cognitive decline. HD gene carriers and their caregivers report the behavioral and cognitive symptoms as the most burdensome. Apathy is the most common behavioral symptom of HD and is related to clinical measures of disease progression, like functional capacity.

Cognitive decline in Huntington's disease expansion gene carriers.

Background: In Huntington's Disease (HD) cognitive decline can occur before unequivocal motor signs become apparent. As cognitive decline often starts early in the course of the disease and has a progressive nature over time, cognition can be regarded as a key target for symptomatic treatment. The specific progressive profile of cognitive decline over time is unknown.

A multi-component cognitive behavioural intervention for the treatment of fear of falling after hip fracture (FIT-HIP): protocol of a randomised controlled trial.

Background: Hip fracture is a common injury in the geriatric population. Despite surgical repair and subsequent rehabilitation programmes, functional recovery is often limited, particularly in individuals with multi-morbidity. This leads to high care dependency and subsequent use of healthcare services.

Decreased cerebral perfusion in Duchenne muscular dystrophy patients.

Duchenne muscular dystrophy is caused by dystrophin gene mutations which lead to the absence of the protein dystrophin. A significant proportion of patients suffer from learning and behavioural disabilities, in addition to muscle weakness. We have previously shown that these patients have a smaller total brain and grey matter volume, and altered white matter microstructure compared to healthy controls.

MRI Susceptibility Changes Suggestive of Iron Deposition in the Thalamus after Ischemic Stroke.

Background: Iron accumulation has been linked to neuronal injury following cerebral ischemia. In animals, a hypointense signal on T2*-weighted (T2*-w) MRI correlated with iron deposits in remote brain regions following ischemic stroke. We aim to assess whether such signal changes are present in remote brain structures following ischemic stroke in humans.

Reliability and factor structure of the Short Problem Behaviors Assessment for Huntington's disease (PBA-s) in the TRACK-HD and REGISTRY studies.

The authors report the inter-rater reliability and factor structure of the Short Problem Behaviors Assessment (PBA-s), a semistructured interview to measure severity and frequency of behavioral problems in Huntington's disease. Video recordings of 410 PBA-s interviews were rescored by an independent rater, and Cohen's kappa calculated to assess inter-rater reliability. The mean kappa was 0.

Microstructural brain abnormalities in Huntington's disease: A two-year follow-up.

Objectives: To investigate both cross-sectional and time-related changes of striatal and whole-brain microstructural properties in different stages of Huntington's disease (HD) using diffusion tensor imaging.

Experimental Design: From the TRACK-HD study, premanifest gene carriers (preHD), early manifest HD and controls were scanned at baseline and 2-year follow-up. Stratification of the preHD group into a far (preHD-A) and near (preHD-B) to predicted disease onset was performed.

Longitudinal metabolite changes in Huntington's disease during disease onset.

Background: Previous cross-sectional magnetic resonance spectroscopy (MRS) studies in Huntington's disease (HD) have demonstrated differences in metabolite concentrations in several regions of interest, especially the putamen and caudate nucleus.

Objective: To assess metabolite changes in both premanifest and early HD over a two year follow up period using MRS at 7 Tesla in several regions of interest.

Methods: In 13 HD gene carriers (10 premanifest and 3 manifest HD) proton MRS was performed at baseline and after 24 months.

Longitudinal resting state fMRI analysis in healthy controls and premanifest Huntington's disease gene carriers: a three-year follow-up study.

Background: We previously demonstrated that in the premanifest stage of Huntington's disease (preHD), a reduced functional connectivity exists compared to healthy controls. In the current study, we look at possible changes in functional connectivity occurring longitudinally over a period of 3 years, with the aim of assessing the potential usefulness of this technique as a biomarker for disease progression in preHD.

Methods: Twenty-two preHD and 17 healthy control subjects completed resting state functional magnetic resonance imaging (fMRI) scans in two visits with 3 years in between.

The potential of composite cognitive scores for tracking progression in Huntington's disease.

Background: Composite scores derived from joint statistical modelling of individual risk factors are widely used to identify individuals who are at increased risk of developing disease or of faster disease progression.

Objective: We investigated the ability of composite measures developed using statistical models to differentiate progressive cognitive deterioration in Huntington's disease (HD) from natural decline in healthy controls.

Methods: Using longitudinal data from TRACK-HD, the optimal combinations of quantitative cognitive measures to differentiate premanifest and early stage HD individuals respectively from controls was determined using logistic regression.

Reduced cerebral gray matter and altered white matter in boys with Duchenne muscular dystrophy.

Objective: Duchenne muscular dystrophy (DMD) is characterized by progressive muscle weakness caused by DMD gene mutations leading to absence of the full-length dystrophin protein in muscle. Multiple dystrophin isoforms are expressed in brain, but little is known about their function. DMD is associated with specific learning and behavioral disabilities that are more prominent in patients with mutations in the distal part of the DMD gene, predicted to affect expression of shorter protein isoforms.

Motor dysfunction influence on executive functioning in manifest and premanifest Huntington's disease.

Motor disturbances can be present in both manifest and premanifest Huntington's disease (HD). We aimed to investigate the role of motor functioning on executive functioning to better understand the progression of cognitive dysfunction in HD. Forty patients with manifest HD, 21 patients with premanifest HD, and a group of 28 controls were tested twice with a 1-year interval.

Eye-of-the-tiger-sign in a 48 year healthy adult.

We report a healthy adult male, who underwent, as a control subject, part of a Huntington's disease study, extensive testing during three visits in a two year follow-up, including clinical examination and 3.0 T MRI scans. The T2-weighted MRI sequences revealed the "eye-of-the-tiger-sign".

The role of iron imaging in Huntington's disease.

Huntington's disease (HD) is a devastating neurological disorder that affects the brain. The cause of HD is an expanded CAG trinucleotide repeat in the Htt gene. The Htt gene is responsible for the protein huntingtin, the exact functions of which have yet to be elucidated.

Reduced functional brain connectivity prior to and after disease onset in Huntington's disease.

Background: Huntington's disease (HD) is characterised by both regional and generalised neuronal cell loss in the brain. Investigating functional brain connectivity patterns in rest in HD has the potential to broaden the understanding of brain functionality in relation to disease progression. This study aims to establish whether brain connectivity during rest is different in premanifest and manifest HD as compared to controls.

Longitudinal pilot-study of Sustained Attention to Response Task and P300 in manifest and pre-manifest Huntington's disease.

Background: Earlier research has found cross-sectional attentional control deficits in manifest Huntington's disease (HD) using neuropsychological testing combined with simultaneous P300 registration. In the current pilot-study, we investigate attentional control in pre-manifest and manifest HD over a 3-year follow-up period.

Method: Five manifest HD (MHD), 9 pre-manifest HD (PMHD), and 12 control subjects were included.

Texture analysis of ultrahigh field T2*-weighted MR images of the brain: application to Huntington's disease.

Purpose: To develop a framework for quantitative detection of between-group textural differences in ultrahigh field T2*-weighted MR images of the brain.

Materials And Methods: MR images were acquired using a three-dimensional (3D) T2*-weighted gradient echo sequence on a 7 Tesla MRI system. The phase images were high-pass filtered to remove phase wraps.

A review of cognition in Huntington's disease.

With the prospect of potential treatments for Huntington's disease (HD), non-invasive markers of disease progression are needed. Cognitive impairment has long been recognised as one of the core symptoms of HD. The first aim of this review is to provide insight into the onset and nature of cognitive loss in the progressing stages of HD.

Quality of life in Huntington's disease: a comparative study investigating the impact for those with pre-manifest and early manifest disease, and their partners.

Background: Given the multifaceted nature of this inherited neurodegenerative condition, typically affecting adults in mid-life, it is perhaps not surprising that studies indicate poorer Health Related Quality of Life (HrQoL) in those with the gene-expansion and, by association, in their families.

Objective: This study aimed to extend the current literature by exploring specific life domains, including at an earlier disease stage than usually reported in the HRQoL literature, and in a subgroup of gene-negative partners.

Methods: 355 participants from the TRACK-HD cohort (120 Controls, 118 Pre-HD and 117 early-HD) completed standardised self-report measures of HrQoL (SF36 and QoLI), underwent clinical assessments of capacity and motor function (UHDRS), semi structured interviews assessing neuropsychiatric symptoms (PBA-s), completed paper and computerized cognitive tasks and assessment of behaviours associated with damage to frontal brain circuits (FrSBe).

Cognition in Huntington's disease in manifest, premanifest and converting gene carriers over ten years.

Background: Cognitive decline in Huntington's disease (HD) remains an area of inconsistencies, especially far from disease onset.

Objective: To clarify the course of cognition in premanifest HD.

Methods: Twenty-six premanifest HD, 19 manifest HD, and 87 control subjects were followed for ten years, using an extensive cognitive battery.

Emotional face recognition deficits and medication effects in pre-manifest through stage-II Huntington's disease.

Facial emotion recognition impairments have been reported in Huntington's disease (HD). However, the nature of the impairments across the spectrum of HD remains unclear. We report on emotion recognition data from 344 participants comprising premanifest HD (PreHD) and early HD patients, and controls.

Evaluation of longitudinal 12 and 24 month cognitive outcomes in premanifest and early Huntington's disease.

Background: Deterioration of cognitive functioning is a debilitating symptom in many neurodegenerative diseases, such as Huntington's disease (HD). To date, there are no effective treatments for the cognitive problems associated with HD. Cognitive assessment outcomes will have a central role in the efforts to develop treatments to delay onset or slow the progression of the disease.

Elevated brain iron is independent from atrophy in Huntington's Disease.

Increased iron in subcortical structures in patients with Huntington's Disease (HD) has been suggested as a causal factor of neuronal degeneration. The present study examines iron accumulation, measured using magnetic resonance imaging (MRI), in premanifest gene carriers and in early HD patients as compared to healthy controls. In total 27 early HD patients, 22 premanifest gene carriers and 25 healthy controls, from the Leiden site of the TRACK-HD study, underwent 3T MRI including high resolution 3D T(1)- and T(2)-weighted and asymmetric spin echo (ASE) sequences.

The structural correlates of functional deficits in early huntington's disease.

Neuropathological studies in Huntington disease (HD) have demonstrated neuronal loss in the striatum, as well as in other brain regions including the cortex. With diffusion tensor MRI we evaluated the hypothesis that the clinical dysfunction in HD is related to regionally specific lesions of circuit-specific cortico-basal ganglia networks rather than to the striatum only. We included 27 HD and 24 controls from the TRACK-HD Paris cohort.

Visual Working Memory Impairment in Premanifest Gene-Carriers and Early Huntington's Disease.

Working memory deficits have been found in Huntington's disease (HD) and in a small group of premanifest (PreHD) gene-carriers. However, the nature and extent of these deficits are unknown. In a large cross-sectional study, we aimed to determine the degree of visuospatial working memory dysfunction across multiple stages of HD.