A useful cognitive motor dual task paradigm in prodromal and manifest Huntington's disease.

Introduction: Individuals with Huntington's disease (HD) experience increased difficulty with balance throughout disease progression. Adding a simultaneous cognitive task to a balance assessment, referred to as a dual task (DT) paradigm, may have a deleterious effect on balance, which can be expressed in terms of a Dual Task Cost (DTC), relative to a single task (ST) condition. The aim of this study is to explore whether a cognitive-motor DT paradigm uncovers balance deficits in prodromal (Pro-HD) and manifest HD, compared to healthy adults (HA).

Mapping neurodegeneration across the Huntington's disease spectrum: a five-year longitudinal analysis of plasma neurofilament light.

Background: Neurofilament light (NfL) has previously been highlighted as a potential biomarker for Huntington's Disease (HD) using cross-sectional analyses. Our study aim was to investigate how longitudinal trajectories of plasma NfL relate to HD disease stage.

Methods: 108 participants [78 individuals with the HD mutation, and 30 healthy controls (HC)] were included in this study.

Exploring bradyphrenia in Huntington's disease using the computerized test of information processing (CTiP).

Background: Bradyphrenia, best thought of as the mental equivalent of bradykinesia, has been described in several disorders of the brain including Parkinson's disease and schizophrenia; however, little is known about this phenomenon in Huntington's Disease (HD).

Objective: The aim of this study was to investigate the presence of bradyphrenia in HD using the Computerized Test of Information Processing (CTiP), an easy to administer and objective task that assesses cognitive processing speed with increasing task complexity.

Methods: This study included 211 participants: Huntington's Disease Integrated Staging System (HD-ISS) Stage 0 [n = 28], Stage 1 [n = 30], Stage 2 [n = 48] and Stage 3 [n = 48], and healthy controls (HC) [n = 57].

Computer simulations predict the impact of neuronal atrophy on the calcium dynamics in Huntington's disease.

One of the early hallmarks of Huntington's disease (HD) is neuronal cell atrophy, especially in the striatum, underlying motor dysfunction in HD. Here using a computer model, we have predicted the impact of cell shrinkage on calcium dynamics at the cellular level. Our model indicates that as cytosolic volume decreases, the amplitude of calcium transients increases and the endoplasmic reticulum (ER) becomes more leaky due to calcium-induced calcium release and a "toxic" positive feedback mechanism mediated by ryanodine receptors that greatly increases calcium release into the cytosol.

LASSI-L detects early cognitive changes in pre-motor manifest Huntington's disease: a replication and validation study.

Background And Objectives: Cognitive decline is an important early sign in pre-motor manifest Huntington's disease (preHD) and is characterized by deficits across multiple domains including executive function, psychomotor processing speed, and memory retrieval. Prior work suggested that the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L)-a verbal learning task that simultaneously targets these domains - could capture early cognitive changes in preHD. The current study aimed to replicate, validate and further analyze the LASSI-L in preHD using larger datasets.

Clinical evaluation of white matter lesions on 3D inversion recovery ultrashort echo time MRI in multiple sclerosis.

Background: We clinically evaluated the quality of white matter lesions (WML) of the cerebrum on 3D inversion recovery ultrashort echo time (IR-UTE) magnetic resonance imaging (MRI) in multiple sclerosis (MS) patients.

Methods: Forty-nine patients with MS were included in this study. A 3T MRI scanner was used.

Plasma NfL as a prognostic biomarker for enriching HD-ISS stage 1 categorisation: a cross-sectional study.

Background: The recently proposed Huntington's Disease Integrated Staging System (HD-ISS) categorises individuals with the Huntintin genetic mutation into disease progression cohorts based on quantitative neuroimaging, cognitive, and functional markers for research purposes. Unfortunately, many research studies do not collect quantitative neuroimaging data, and so the authors of the HD-ISS have subsequently provided approximated cohort thresholds based on disease and clinical data alone. However, these are rough proxies that aim to maximise stage separation, and should not be considered as 1:1 substitutes for the HD-ISS.

Graphomotor Dysfluency as a Predictor of Disease Progression in Premanifest Huntington's Disease.

Background: Prior studies have relied on conventional observer-based severity ratings such as the Unified Huntington's Disease Rating Scale (UHDRS) to identify early motor markers of decline in Huntington's disease (HD).

Objective: The present study examined the predictive utility of graphomotor measures handwriting and drawing movements.

Methods: Seventeen gene-positive premanifest HD subjects underwent comprehensive clinical, cognitive, motor, and graphomotor assessments at baseline and at follow-up intervals ranging from 9-36 months.

The signal intensity variation of multiple sclerosis (MS) lesions on magnetic resonance imaging (MRI) as a potential biomarker for patients' disability: A feasibility study.

Introduction: Although many lesion-based MRI biomarkers in multiple sclerosis (MS) patients were investigated, none of the previous studies dealt with the signal intensity variations (SIVs) of MS lesions. In this study, the SIVs of MS lesions on direct myelin imaging and standard clinical sequences as possible MRI biomarkers for disability in MS patients were assessed.

Methods: Twenty seven MS patients were included in this prospective study.

Development and Psychometric Properties of a New Brief, Yet Comprehensive, Behavioral Questionnaire for Huntington's Disease.

Background: Individuals with Huntington's disease (HD) experience motoric, cognitive, and psychiatric dysfunction. These difficulties can cause maladaptive behaviors that can be very distressing to family and caregivers. Capturing these behaviors in clinical and research settings is crucial.

Salivary Huntingtin protein is uniquely associated with clinical features of Huntington's disease.

Measuring Huntingtin (HTT) protein in peripheral cells represents an essential step in biomarker discovery for Huntington's Disease (HD), however to date, investigations into the salivary expression of HTT has been lacking. In the current study, we quantified total HTT (tHTT) and mutant HTT (mHTT) protein in matched blood and saliva samples using single molecule counting (SMC) immunoassays: 2B7-D7F7 (tHTT) and 2B7-MW1 (mHTT). Matched samples, and clinical data, were collected from 95 subjects: n = 19 manifest HD, n = 34 premanifest HD (PM), and n = 42 normal controls (NC).

Anosognosia in HD: Comparison of self-report and caregiver ratings with objective performance measures.

Introduction: Individuals with Huntington's disease (HD) commonly experience anosognosia, a lack of awareness of deficits. Thus, it is important to examine the accuracy of patient vs caregiver ratings on the basis of objective performance-based measures.

Methods: The Anosognosia Scale (AS) was given to 33 patients with manifest HD and their caregivers.

Assessing the state of care for Huntington disease in the United States: Results from a survey of practices treating Huntington disease patients.

Background: No study to date has thoroughly examined US Huntington disease (HD) care delivery in a variety of clinic settings by HD specialists and non-specialists.

Objective: To obtain a clearer understanding of current care structure and delivery of care through a survey of representative US physicians treating HD patients.

Methods: We designed and fielded a survey of 40 closed-ended evaluative items and one open-ended item to a sample of 339 US practices.

Differences in body sway can be identified in Huntington's disease using a practical balance assessment device.

Introduction: Huntington's disease (HD) is a progressive neurodegenerative disorder with motor, cognitive, and psychiatric symptoms that typically manifest in middle adulthood. Balance assessments may be useful for predicting disease onset and progression, but studies are limited. We aimed to enhance estimates of HD onset using an inexpensive and practical body sway assessment device [i.

Source recognition discriminability impairment in Huntington's versus Alzheimer's disease: Evidence from the CVLT-3.

Research suggests that individuals with Huntington's disease (HD) perform better than individuals with Alzheimer's disease (AD) on the California Verbal Learning Test (CVLT) Yes/No Recognition trial. However, those with HD have been shown to have deficits comparable to those with AD on the Source Recognition Discriminability (RD) index (which assesses the ability to distinguish between List A targets and List B distractors), suggesting that HD may involve selective impairment in aspects of yes/no recognition that rely on source memory. However, whether individuals with HD and AD show comparable deficits on Source RD across stages of dementia severity has not been adequately investigated.

The Repeatable Battery for the Assessment of Neuropsychological Status, While Useful for Measuring Cognitive Changes in Manifest Huntington Disease, May Show Limited Utility in Premanifest Disease.

Background: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a brief, standardized neuropsychological test that assesses several areas of cognitive function. Recent studies, although sparse, have examined the use of the RBANS to detect cognitive deficits in individuals with manifest Huntington disease (HD); however, no studies have investigated its utility to detect cognitive deficits in individuals with premanifest HD (PreHD), where cognitive symptoms are thought to be more subtle.

Objective: To assess cognitive deficits in individuals with HD, particularly in individuals with PreHD, using an easily administered, brief but comprehensive, neuropsychological test.

Myelin water imaging using a short-TR adiabatic inversion-recovery (STAIR) sequence.

Purpose: To develop a new myelin water imaging (MWI) technique using a short-TR adiabatic inversion-recovery (STAIR) sequence on a clinical 3T MR scanner.

Methods: Myelin water (MW) in the brain has both a much shorter T and a much shorter T * than intracellular/extracellular water. A STAIR sequence with a short TR was designed to efficiently suppress long T signals from intracellular/extracellular water, and therefore allow selective imaging of MW, which has a much shorter T .

Associations between prognostic index scores and plasma neurofilament light in Huntington's disease.

Introduction: The inclusion of premanifest Huntington's Disease (Pre-HD) subjects in clinical trials necessitates selecting those who are near transition to manifest Huntington's disease (Man-HD). We previously determined that plasma neurofilament light (NfL) levels are significantly correlated with predicted years to Man-HD onset, using established formulae. Recently, a new normalized prognostic index (PIN) score for predicting Pre-HD disease progression has been validated.

Plasma neurofilament light in Huntington's disease: A marker for disease onset, but not symptom progression.

Objective: To investigate whether plasma NfL levels correlate with clinical symptom severity in premanifest (PM) and manifest HD (HD) individuals, and whether a NfL cut-point could distinguish PM from HD patients with reasonable accuracy.

Method: 98 participants (33 control, 26 PM, 39 HD), underwent blood sample collection and clinical assessment, using both UHDRS and non-UHDRS measures, at one academic HD Center. Years to onset (YTO), probability of disease onset in 5 years, and predicted years until 60% onset probability were also calculated.

Inversion Recovery Ultrashort TE MR Imaging of Myelin is Significantly Correlated with Disability in Patients with Multiple Sclerosis.

Background And Purpose: MR imaging has been widely used for the noninvasive evaluation of MS. Although clinical MR imaging sequences are highly effective in showing focal macroscopic tissue abnormalities in the brains of patients with MS, they are not specific to myelin and correlate poorly with disability. We investigated direct imaging of myelin using a 2D adiabatic inversion recovery ultrashort TE sequence to determine its value in assessing disability in MS.

Central Cognitive Processing Speed Is an Early Marker of Huntington's Disease Onset.

Background: Several studies have suggested that cognitive processing speed may be useful for assessing early cognitive change in premanifest Huntington's disease (HD); however, current measures lack the ability to control for the effects of motor dysfunction commonly found in HD. The Computerized Test of Information Processing (CTiP) is a rapidly administered computerized tool that allows for the examination of central cognitive processing speed by using motor-corrected scores to account for motor dysfunction.

Objective: To examine central cognitive processing speed as an early marker of HD onset using the CTiP.

Levels of Interleukin-6 in Saliva, but Not Plasma, Correlate with Clinical Metrics in Huntington's Disease Patients and Healthy Control Subjects.

Growing evidence suggests that inflammatory responses, in both the brain and peripheral tissues, contribute to disease pathology in Huntington's disease (HD), an inherited, progressive neurodegenerative disorder typically affecting adults in their 30-40 s. Hence, studies of inflammation-related markers in peripheral fluids might be useful to better characterize disease features. In this study, we measured levels of C-reactive protein (CRP), Interleukin-6 (IL-6), interleukin 1 beta (IL-1B), and alpha-amylase (AA) in saliva and plasma from = 125 subjects, including = 37 manifest HD patients, = 36 premanifest patients, and = 52 healthy controls, using immunoassays.

Myelin Imaging in Human Brain Using a Short Repetition Time Adiabatic Inversion Recovery Prepared Ultrashort Echo Time (STAIR-UTE) MRI Sequence in Multiple Sclerosis.

Background Water signal contamination is a major challenge for direct ultrashort echo time (UTE) imaging of myelin in vivo because water contributes most of the signals detected in white matter. Purpose To validate a new short repetition time (TR) adiabatic inversion recovery (STAIR) prepared UTE (STAIR-UTE) sequence designed to suppress water signals and to allow imaging of ultrashort T2 protons of myelin in white matter using a clinical 3-T scanner. Materials and Methods In this prospective study, an optimization framework was used to obtain the optimal inversion time for nulling water signals using STAIR-UTE imaging at different TRs.