Impairments to executive function in emerging adults with Huntington disease.

BACKGROUND AND OBJECTIVES: The clinical diagnosis of Huntington disease (HD) is typically made once motor symptoms and chorea are evident. Recent reports highlight the onset of cognitive and psychiatric symptoms before motor manifestations. These findings support further investigations of cognitive function across the lifespan of HD sufferers. METHODS: To assess cognitive symptoms in the developing brain, we administered assessments from the National Institutes of Health Toolbox Cognitive Battery, an age-appropriate cognitive assessment with population norms, to a cohort of children, adolescents and young adults with (gene-expanded; GE) and without (gene-not-expanded; GNE) the trinucleotide cytosine, adenine, guanine (CAG) expansion in the Huntingtin gene. These five assessments that focus on executive function are well validated and form a composite score, with population norms. We modelled these scores across age, and CAP score to estimate the slope of progression, comparing these results to motor symptoms. RESULTS: We find significant deficits in the composite measure of executive function in GE compared with GNE participants. GE participant performance on working memory was significantly lower compared with GNE participants. Modelling these results over age suggests that these deficits occur as early as 18 years of age, long before motor manifestations of HD. CONCLUSIONS: This work provides strong evidence that impairments in executive function occur as early as the second decade of life, well before anticipated motor onset. Future investigations should delineate whether these impairments in executive function are due to abnormalities in neurodevelopment or early sequelae of a neurodegenerative process.

Inhibitory control, working memory and coping with stress: Associations with symptoms of anxiety and depression in adults with Huntington's disease.

OBJECTIVE: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by neuropsychiatric symptoms (e.g., anxiety and depression), where individuals suffer high levels of stress from the social, physical, and cognitive burden of the disease. The present study examined two factors associated with increased risk for symptoms of anxiety and depression: executive function skills (inhibitory control/attention and working memory) and skills to cope with stress. METHOD: Adults with HD completed the NIH Toolbox measures of inhibitory control/attention and working memory, as well as self-report measures of coping with HD-related stress and symptoms of anxiety and depression. Path analyses were used to test direct and indirect associations among the subtypes of executive functioning, coping, and symptoms. RESULTS: No significant associations were found in the full sample (n = 47), due to a significant portion of the sample with very low executive function abilities. Additional analyses were conducted on a subset of the sample (participants in the top three quartiles on both measures of executive functioning, n = 32). Significant indirect associations emerged among inhibitory control/attention skills, secondary control coping (e.g., acceptance and reappraisal), and symptoms of anxiety and depression in the subsample. Higher inhibitory control/attention skills were associated with greater use of secondary control coping, and greater use of these coping skills was related to lower symptoms of anxiety and depression. No direct or indirect associations were found among working memory skills, coping, and symptoms of anxiety and depression. CONCLUSIONS: Implications for interventions to enhance executive function and coping skills in adults with HD are highlighted. (PsycInfo Database Record (c) 2022 APA, all rights reserved).