Composite <scp>UHDRS</scp> Correlates With Progression of Imaging Biomarkers in Huntington's Disease

Estévez-Fraga, Carlos; Scahill, Rachael I.; Dürr, Alexandra; Leavitt, Blair R.; Roos, Raymund A.C.; Langbehn, Douglas R.; Rees, Geraint; Gregory, Sarah; Tabrizi, Sarah J.

doi:10.1002/mds.28489

Cited by 16 publications

(21 citation statements)

References 39 publications

(78 reference statements)

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“…This composite score is a multidimensional measure of progression in HD being used as a primary outcome in clinical trials. 6 Interestingly, direct NfL‐by‐sex interactions on motor or psychiatric symptoms were not observed in our sample. However, as expected, in an indirect manner, the integrity in the brain regions showing a significant NfL‐by‐sex interaction correlated with motor, cognitive, and psychiatric symptoms.…”

Section: Discussionmentioning

confidence: 55%

“…From a clinical perspective, the NfL‐by‐sex interaction on cUHDRS is noteworthy. This composite score is a multidimensional measure of progression in HD being used as a primary outcome in clinical trials 6 . Interestingly, direct NfL‐by‐sex interactions on motor or psychiatric symptoms were not observed in our sample.…”

Section: Discussionmentioning

confidence: 58%

“…Finally, composite UHDRS (cUHDRS) scores were computed, given its improved performance as a measure of disease progression in HD. 6 …”

Section: Methodsmentioning

confidence: 99%

“…Total functional capacity (TFC) and motor symptoms (TMS) were recorded from the Unified Huntington’s Disease Rating Scale (UHDRS). The following cognitive and neuropsychiatric indicators, known to be sensitive to HD progression with minimal medication‐related alterations, 5,6 were included: Symbol Digit Modality Test (SDMT), Stroop‐word task, and the apathy score of the Problem Behavior Assessment (PBA). Finally, composite UHDRS (cUHDRS) scores were computed, given its improved performance as a measure of disease progression in HD 6 …”

Section: Methodsmentioning

confidence: 99%

“…Finally, composite UHDRS (cUHDRS) scores were computed, given its improved performance as a measure of disease progression in HD. 6 Biomarker and neuroimaging procedures CSF samples were collected, processed, aliquoted in polypropylene tubes, and frozen at −80°C until analysis according to international consensus recommendations. 7 NfL levels were measured with the NF-light Advantage kit (Cat# 103186) using the Single Molecule Array (Simoa) technology (Simoa; Quanterix, Lexington, MA, USA) in the Biomarker detection system by following the manufacturer's instructions.…”

Section: Sample and Assessmentsmentioning

confidence: 99%

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Interaction between sex and neurofilament light chain on brain structure and clinical severity in Huntington’s disease

Sampedro

Martínez‐Horta

Pérez‐Pérez

et al. 2021

Ann Clin Transl Neurol

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Female Huntington's disease (HD) patients have consistently shown a faster clinical worsening than male, but the underlying mechanisms responsible for this observation remain unknown. Here, we describe how sex modifies the impact of neurodegeneration on brain atrophy and clinical severity in HD. Cerebrospinal fluid neurofilament light chain (NfL) levels were used as a biological measure of neurodegeneration, and brain atrophy was assessed by structural magnetic resonance imaging. We found that larger NfL values in women reflect higher brain atrophy and clinical severity than in men (p < 0.05 for an interaction model). This differential vulnerability could have important implications in clinical trials.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 58%

“…Finally, composite UHDRS (cUHDRS) scores were computed, given its improved performance as a measure of disease progression in HD. 6 …”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Sample and Assessmentsmentioning

confidence: 99%

See 3 more Smart Citations

Interaction between sex and neurofilament light chain on brain structure and clinical severity in Huntington’s disease

Sampedro

Martínez‐Horta

Pérez‐Pérez

et al. 2021

Ann Clin Transl Neurol

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Modifiable factors associated with Huntington's disease progression in presymptomatic participants

Gil‐Salcedo,

Massart,

de Langavant

et al. 2024

Ann Clin Transl Neurol

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ObjectiveHuntington's disease (HD) is a neurodegenerative disorder characterized by progressive motor, cognitive, and psychiatric symptoms. Our aim here was to identify factors that can be modified to slow disease progression even before the first symptoms appear.MethodsWe included 2636 presymptomatic individuals (comparison with family controls) drawn from the prospective observational cohort Enroll‐HD, with more than 35 CAG repeats and at least two assessments of disease progression measured with the composite Huntington's disease rating Scale (cUHDRS). The association between sociodemographic factors, health behaviors, health history, and cUHDRS trajectory was assessed with a mixed‐effects random forest using partial dependence plots and Shapley additive explanation method.ResultsParticipants were followed by an average of 3.4 (SD = 1.97) years. We confirmed the negative impact of age and a high number of CAG repeats. We found that a high level of education, a body mass index (BMI) <23 kg/m2 before the age of 40 and >23 kg/m2 thereafter, alcohol consumption of <15 units per week, current coffee consumption and no smoking were linked to slow disease progression, as did no previous exposure to antidepressants or anxiolytic, no psychiatric history or comorbidities, and being female. Other comorbidities or marital status showed no major association with HD evolution.InterpretationReducing modifiable risk factors for HD is one way to support the presymptomatic population. A high level of education, low‐to‐moderate alcohol consumption, no smoking, and BMI control are likely to slow disease progression in this population.

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Progressive alterations in white matter microstructure across the timecourse of Huntington's disease

et al. 2023

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Background Whole‐brain longitudinal diffusion studies are crucial to examine changes in structural connectivity in neurodegeneration. Here, we investigated the longitudinal alterations in white matter (WM) microstructure across the timecourse of Huntington's disease (HD). Methods We examined changes in WM microstructure from premanifest to early manifest disease, using data from two cohorts with different disease burden. The TrackOn‐HD study included 67 controls, 67 premanifest, and 10 early manifest HD (baseline and 24‐month data); the PADDINGTON study included 33 controls and 49 early manifest HD (baseline and 15‐month data). Longitudinal changes in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity from baseline to last study visit were investigated for each cohort using tract‐based spatial statistics. An optimized pipeline was employed to generate participant‐specific templates to which diffusion tensor imaging maps were registered and change maps were calculated. We examined longitudinal differences between HD expansion‐carriers and controls, and correlations with clinical scores, including the composite UHDRS (cUHDRS). Results HD expansion‐carriers from TrackOn‐HD, with lower disease burden, showed a significant longitudinal decline in FA in the left superior longitudinal fasciculus and an increase in MD across subcortical WM tracts compared to controls, while in manifest HD participants from PADDINGTON, there were significant widespread longitudinal increases in diffusivity compared to controls. Baseline scores in clinical scales including the cUHDRS predicted WM microstructural change in HD expansion‐carriers. Conclusion The present study showed significant longitudinal changes in WM microstructure across the HD timecourse. Changes were evident in larger WM areas and across more metrics as the disease advanced, suggesting a progressive alteration of WM microstructure with disease evolution.

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Composite UHDRS Correlates With Progression of Imaging Biomarkers in Huntington's Disease

Cited by 16 publications

References 39 publications

Interaction between sex and neurofilament light chain on brain structure and clinical severity in Huntington’s disease

Interaction between sex and neurofilament light chain on brain structure and clinical severity in Huntington’s disease

Modifiable factors associated with Huntington's disease progression in presymptomatic participants

Progressive alterations in white matter microstructure across the timecourse of Huntington's disease

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