Concurrent Cross-Sectional and Longitudinal Analyses of Multivariate White Matter Profiles and Clinical Functioning in Pre-Diagnosis Huntington Disease.

Background: Gray matter (GM) atrophy in the striatum and across the brain is a consistently reported feature of the Huntington Disease (HD) prodrome. More recently, widespread prodromal white matter (WM) degradation has also been detected. However, longitudinal WM studies are limited and conflicting, and most analyses comparing WM and clinical functioning have also been cross-sectional.

Apathy Is Related to Cognitive Control and Striatum Volumes in Prodromal Huntington's Disease.

Objectives: Apathy is a debilitating symptom of Huntington's disease (HD) and manifests before motor diagnosis, making it an excellent therapeutic target in the preclinical phase of Huntington's disease (prHD). HD is a neurological genetic disorder characterized by cognitive and motor impairment, and psychiatric abnormalities. Apathy is not well characterized within the prHD.

Dynamic functional network connectivity in Huntington's disease and its associations with motor and cognitive measures.

Dynamic functional network connectivity (dFNC) is an expansion of traditional, static FNC that measures connectivity variation among brain networks throughout scan duration. We used a large resting-state fMRI (rs-fMRI) sample from the PREDICT-HD study (N = 183 Huntington disease gene mutation carriers [HDgmc] and N = 78 healthy control [HC] participants) to examine whole-brain dFNC and its associations with CAG repeat length as well as the product of scaled CAG length and age, a variable representing disease burden. We also tested for relationships between functional connectivity and motor and cognitive measurements.

High and Low Levels of an NTRK2-Driven Genetic Profile Affect Motor- and Cognition-Associated Frontal Gray Matter in Prodromal Huntington's Disease.

This study assessed how (brain-derived neurotrophic factor) and other genes involved in its signaling influence brain structure and clinical functioning in pre-diagnosis Huntington's disease (HD). Parallel independent component analysis (pICA), a multivariate method for identifying correlated patterns in multimodal datasets, was applied to gray matter concentration (GMC) and genomic data from a sizeable PREDICT-HD prodromal cohort ( = 715). pICA identified a genetic component highlighting , which encodes BDNF's TrkB receptor, that correlated with a GMC component including supplementary motor, precentral/premotor cortex, and other frontal areas ( < 0.

Genetics Modulate Gray Matter Variation Beyond Disease Burden in Prodromal Huntington's Disease.

Huntington's disease (HD) is a neurodegenerative disorder caused by an expansion mutation of the cytosine-adenine-guanine (CAG) trinucleotide in the gene. Decline in cognitive and motor functioning during the prodromal phase has been reported, and understanding genetic influences on prodromal disease progression beyond CAG will benefit intervention therapies. From a prodromal HD cohort ( = 715), we extracted gray matter (GM) components through independent component analysis and tested them for associations with cognitive and motor functioning that cannot be accounted for by CAG-induced disease burden (cumulative effects of CAG expansion and age).

Whole-Brain Connectivity in a Large Study of Huntington's Disease Gene Mutation Carriers and Healthy Controls.

Huntington's disease (HD) is an inherited brain disorder characterized by progressive motor, cognitive, and behavioral dysfunctions. It is caused by abnormally large trinucleotide cytosine-adenine-guanine (CAG) repeat expansions on exon 1 of the Huntingtin gene. CAG repeat length (CAG-RL) inversely correlates with an earlier age of onset.

Patterns of Co-Occurring Gray Matter Concentration Loss across the Huntington Disease Prodrome.

Huntington disease (HD) is caused by an abnormally expanded cytosine-adenine-guanine (CAG) trinucleotide repeat in the gene. Age and CAG-expansion number are related to age at diagnosis and can be used to index disease progression. However, observed onset-age variability suggests that other factors also modulate progression.