Predictors of Working Capacity Changes Related to Huntington’s Disease: A Longitudinal Study

Abstract

Background: Huntington’s disease (HD) is an inherited neurodegenerative disorder that is characterized by motor, cognitive, and psychiatric symptoms. Although 65%of HD expanded gene carriers report changes in employment as the first functional loss, little is known about the predictors leading to changes of working capacity. Given the impact on quality of life, understanding of these factors is of great clinical value. Objective: This study evaluates disease specific characteristics and their predictive value in loss of working capacity in HD. Methods: Longitudinal data was collected through the worldwide observational study (Enroll-HD), with 15,301 participants in total and 2,791 HD and healthy control participants meeting the inclusion criteria. Changes in working capacity were analyzed by means of a survival analysis. Predictive values of demographic factors and clinical characteristics were assessed for premanifest and manifest HD through Cox regressions. Results: HD expanded gene carriers, manifest and premanifest combined, had a 31%chance of experiencing changes in employment after three years, compared to 4%in healthy controls. Apathy was found to be the most crucial determinant of working capacity changes in premanifest HD, while executive and motor dysfunction play an important role in manifest HD. Conclusion: HD expanded gene carriers are more likely to lose working capacity compared to healthy controls. Disease progression, altered motor function, cognitive decline, and in an early stage of the disease apathetic symptoms are indicative of negative changes in working capacity. Clinicians should recognize that early disease related changes, especially apathy, can affect working capacity.

Protocol for a randomised controlled feasibility trial of HD-DRUM, a rhythmic movement training application for cognitive and motor symptoms in people with Huntington’s disease

“…Participants will be assessed in the following tests that have been shown sensitive to cognitive 6 and motor symptoms in HD 25 26 . The testing session will take approximately two hours including breaks.…”

“…Huntington’s disease (HD) is a genetic neurodegenerative disease that leads to the progressive loss of cognitive and motor abilities, largely due to basal ganglia (BG) atrophy. Striatal atrophy 1 and microstructural alterations in white matter (WM) connections 2 with associated cognitive control dysfunctions 3–5 occur many years before the clinical onset of motor symptoms and will eventually negatively impact a person’s ability to live independently 6 .…”

Medial prefrontal transcranial alternating current stimulation for apathy in Huntington’s disease

“…The TFC is a clinician rating of how the person with HD is functioning across the domains of occupation, finances, domestic chores, activities of daily living, and care level (Beglinger et al 2010, Shoulson and Fahn 1979). Our choice to recruit people in the late premanifest and early manifest stages of the disease continuum reflected the prevalence and functional impact of apathy and mild cognitive impairment during these stages, when the person with HD is continuing to participate in home, work, and social activities (Fritz et al 2018, Jacobs, Hart, and Roos 2018, Van Der Zwaan et al 2021).…”

HD-DRUM, a Tablet-Based Drumming Training App Intervention for People With Huntington Disease: App Development Study

“…Striatal atrophy [ 1 ] and white matter degeneration [ 2 ] are observed many years before the onset of movement symptoms. These early brain changes are accompanied by impairments in psychomotor speed and executive functions [ 3 , 4 ] including problems in decision-making, multitasking, and motor sequence learning, all of which may hamper a person’s everyday functional abilities such as working capacity [ 5 ].…”