"Frontal" Behaviors Before the Diagnosis of Huntington's Disease and Their Relationship to Markers of Disease Progression: Evidence of Early Lack of Awareness

Duff, Kevin; Paulsen, Jane S.; Beglinger, Leigh J.; Langbehn, Douglas R.; Wang, Chiachi; Stout, Julie C.; Ross, Christopher A.; Aylward, Elizabeth H.; Carlozzi, Noelle E.; Queller, Sarah

doi:10.1176/appi.neuropsych.22.2.196

Cited by 98 publications

(137 citation statements)

References 30 publications

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“…Furthermore, we know that a small portion of our sample (largely our later-stage participants) were more likely to have incomplete survey data; some of this data loss was due to participant fatigue, while other data loss was due to practical limitations related to exceeding study visit lengths for reserved testing space (and an inability to complete the assessment outside of the clinic visit). Thus, additional work is needed to determine when self-report becomes unreliable [89]. …”

Section: Discussionmentioning

confidence: 99%

HDQLIFE: development and assessment of health-related quality of life in Huntington disease (HD)

et al. 2016

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Purpose Huntington disease (HD) is a chronic, debilitating genetic disease that affects physical, emotional, cognitive, and social health. Existing patient-reported outcomes (PROs) of health-related quality of life (HRQOL) used in HD are neither comprehensive, nor do they adequately account for clinically meaningful changes in function. While new PROs examining HRQOL (i.e., Neuro-QoL—Quality of Life in Neurological Disorders and PROMIS—Patient-Reported Outcomes Measurement Information System) offer solutions to many of these shortcomings, they do not include HD-specific content, nor have they been validated in HD. HDQLIFE addresses this by validating 12 PROMIS/Neuro-QoL domains in individuals with HD and by using established PROMIS methodology to develop new, HD-specific content. Methods New item pools were developed using cognitive debriefing with individuals with HD, and expert, literacy, and translatability reviews. Existing item banks and new item pools were field tested in 536 individuals with prodromal, early-, or late-stage HD. Results Moderate to strong relationships between Neuro-QoL/PROMIS measures and generic self-report measures of HRQOL, and moderate relationships between Neuro-QoL/PROMIS and clinician-rated measures of similar constructs supported the validity of Neuro-QoL/PROMIS in individuals with HD. Exploratory and confirmatory factor analysis, item response theory, and differential item functioning analyses were utilized to develop new item banks for Chorea, Speech Difficulties, Swallowing Difficulties, and Concern with Death and Dying, with corresponding six-item short forms. A four-item short form was developed for Meaning and Purpose. Conclusions HDQLIFE encompasses both validated Neuro-QoL/PROMIS measures, as well as five new scales in order to provide a comprehensive assessment of HRQOL in HD.

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Section: Discussionmentioning

confidence: 99%

HDQLIFE: development and assessment of health-related quality of life in Huntington disease (HD)

et al. 2016

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“…Executive function and working memory are especially vulnerable to early brain changes in pmHD (Duff et al 2010; Hart et al 2011; Stout et al 2011). We assessed cognitive function in these domains by using the National Institutes of Health (NIH) EXAMINER (Kramer et al 2014) Executive Composite and Working Memory Score.…”

Section: Methodsmentioning

confidence: 99%

Surface-based morphometry reveals caudate subnuclear structural damage in patients with premotor Huntington disease

Kim

Possin

et al. 2016

Brain Imaging and Behavior

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In patients with premotor Huntington’s disease (pmHD), literature has reported decreases in caudate volume. However, the regional vulnerability of the caudate nucleus to pmHD remains to be clarified. We aimed to determine whether regional structural damage of the caudate nucleus was present in pmHD and was correlated with clinical profile using a surface-based morphometric technique applied to T1-weighted MRI. The study cohort consisted of 14 volunteers with genetically confirmed pmHD (6 males; 41.8 ± 13.2 years) and 11 age- and sex-matched controls (5 males; 46.2 ± 11.9 years, p > 0.3). On 3-T T1-weighted images, bilateral caudate volumes were manually delineated. The resulting labels were converted to a surface, triangulated with 1002 points equally distributed across subjects using SPHARM-PDM. Displacement vectors were then computed between each individual and a template surface representing the whole cohort. Computing point-wise Jacobian determinants (JD) from these vectors quantified local volumes. We found decreases in bilateral global caudate volumes in the pmHD group compared to controls (t = 3.4; p = 0.002). Point-wise analysis of local volumes mapped caudate atrophy in pmHD primarily onto medial surface (t > 2.7; FDR < 0.05), with most pronounced changes in anteromedial subdivision. In a combined group of patients and controls, volume within the area presenting significant group difference was positively correlated with scores of executive function (r = 0.7; p < 0.001) and working memory (r = 0.6; p = 0.002). In patients, the caudate atrophy was associated with increase in disease burden (r = 0.7; p = 0.005). Caudate subnuclear atrophy measured using our surface-based morphometric technique is evident in pmHD, correlates with clinical variables, and may provide a more sensitive biomarker than global volumes.

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“…For example, measures of executive functioning, including speed/inhibition, verbal working memory, verbal learning and memory, motor planning, sensory-perceptual processing, and attention and information integration are all sensitive to worsening of cognitive function in people with prodromal HD in the Medium and High CAP groups (Harrington et al, 2012). Impaired elements of executive function have been reported in prodromal HD on a wide variety of cognitive tasks (Duff et al, 2010; Papp et al, 2013). Furthermore, baseline ratings by companions of participants’ everyday executive function in the Medium and High groups are consistent with findings reported by Paulsen et al (2013) who examined longitudinal change in the CAP groups, and by Peavy et al (2010), who noted attention measures are among those which better define the onset of functional decline in HD.…”

Section: Discussionmentioning

confidence: 99%

Everyday cognition in prodromal Huntington disease.

Williams¹,

Kim²,

Downing³

et al. 2015

Neuropsychology

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Objective Assessment of daily functions affected by cognitive loss in prodromal Huntington disease (HD) is necessary in practice and clinical trials. We evaluated baseline and longitudinal sensitivity of the Everyday Cognition (ECog) scales in prodromal HD and compared self- and companion-ratings. Method Everyday cognition was self-assessed by 850 participants with prodromal HD and 768 companions. We examined internal structure using confirmatory factor analysis (CFA) on baseline data. For longitudinal analysis, we stratified participants into Low, Medium, and High disease progression groups. We examined ECog scores for group differences and participant-and-companion differences using linear mixed effects regression (LMER). Comparison with the Total Functional Capacity (TFC) scale was made. Results CFA revealed good fit of a 5-factor model having a global factor (total score), and sub factors (subscales) of memory, language, visuospatial perception, and executive function. At study entry, participants and companions in the Medium and High groups reported significantly worsened everyday cognition as well as significant functional decline over time. Losses became more pronounced and participant and companion ratings diverged as individuals progressed. TFC showed significant functional loss over time in the High group but not in the Medium group. Conclusions Disease progression is associated with reduced self- and companion-reported everyday cognition in prodromal HD participants who are less than 13 years to estimated motor onset. Our findings suggest companion ratings are more sensitive than participants’ for detecting longitudinal change in daily cognitive function. ECog appears more sensitive to specific functional changes in the prodrome of HD than the TFC.

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"Frontal" Behaviors Before the Diagnosis of Huntington's Disease and Their Relationship to Markers of Disease Progression: Evidence of Early Lack of Awareness

Cited by 98 publications

References 30 publications

HDQLIFE: development and assessment of health-related quality of life in Huntington disease (HD)

HDQLIFE: development and assessment of health-related quality of life in Huntington disease (HD)

Surface-based morphometry reveals caudate subnuclear structural damage in patients with premotor Huntington disease

Everyday cognition in prodromal Huntington disease.

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