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This study aims to give an overview of the number of prenatal tests for Huntington's disease ( HD), test results, and pregnancy outcomes in the Netherlands between 1998 and 2008 and to compare them with available data from the period 1987 to 1997. A total of 126 couples underwent prenatal diagnosis ( PND) on 216 foetuses: 185 (86%) direct tests and 31 (14%) exclusion tests. In 9% of direct tests the risk for the foetus was 25%. Four at-risk parents (4%) carried intermediate alleles. Ninety-one foetuses had CAG expansions ≥36% or 50% risk haplotypes: 75 (82%) were terminated for HD, 12 (13%) were carried to term; four pregnancies were miscarried, terminated for other reasons or lost to follow-up. Unaffected pregnancies (122 foetuses) resulted in the birth of 112 children. The estimated uptake of PND was 22% of CAG expansion carriers (≥36 repeats) at reproductive age. PND was used by two new subgroups: carriers of intermediate alleles and 50% at-risk persons opting for a direct prenatal test of the foetus. A significant number of HD expansion or 50% risk pregnancies were continued. Speculations were made on causative factors contributing to these continuations. Further research on these couples' motives is needed. [ABSTRACT FROM AUTHOR]

We aimed to study reproductive behaviour of couples opting for prenatal diagnosis ( PND) and pre-implantation genetic diagnosis ( PGD) for Huntington's disease ( HD). In the Netherlands, exclusion PND is available for persons at 50% risk, whereas exclusion PGD is not allowed. All 162 couples who underwent PND or PGD for HD between 1998 and 2008 and referrals for exclusion PGD to Belgium were included. Couples' reproductive information was collected until December 2010; 132 couples (81.5%) underwent PND in 262 pregnancies, 54 (33.3%) started PGD, and 25 used both. Sixteen percent of PND couples used exclusion PND and 6% used exclusion PGD. The outcomes were 76.5% of PND couples delivered ≥1 unaffected child(ren) after PND, and 44.4% of PGD couples delivered ≥1 PGD child(ren) (mean 2.5 cycles/couple). Couples opting for PGD secondarily (after a previous pregnancy) had more frequently terminated a pregnancy for HD (87.0%) compared with couples secondarily opting for PND (55.2%; p = 0.015). At-risk or HD expansion carrier males were underrepresented in the group of couples primarily opting for PGD (25%) and overrepresented in the secondary PGD group (64%). We conclude that couples reconsider their choices in every subsequent pregnancy based on their previous experience, personal beliefs and the gender of the at-risk partner. [ABSTRACT FROM AUTHOR]

van Rij MC, de Die-Smulders CEM, Bijlsma EK, de Wert GMWR, Geraedts JP, Roos RAC, Tibben A. Evaluation of exclusion prenatal and exclusion preimplantation genetic diagnosis for Huntington's disease in the Netherlands. Individuals at 50% risk of Huntington's disease (HD) who prefer not to know their carrier status, might opt for exclusion prenatal diagnosis (ePND) or exclusion preimplantation genetic diagnosis (ePGD). This study aims to provide a better understanding of couples' motives for choosing ePND or ePND, and surveys couples' experiences in order to make recommendations for the improvement of counselling for exclusion testing. This qualitative retrospective interview study focussed on couples who underwent ePND or ePGD for HD in the period 1996-2010. Seventeen couples were included of which 13 had experienced ePND and 6 ePGD. Mean time-interval since exclusion-testing was 3.9 years. Couples' moral reservations regarding termination of pregnancy (TOP) or discarding healthy embryos were counterbalanced by the wish to protect their future child against HD. Seven couples had terminated a total of 11 pregnancies with a 50% HD risk, none showed regret. ePGD was used by couples who wanted to avoid (another) TOP. ePND and ePGD are acceptable reproductive options for a specific group of counsellees. To guarantee sound standards of care, it is imperative that candidate couples be given in-depth non-directive counselling about all possible scenarios, and adequate professional and psychological support prior to, during and after ePND/ePGD. [ABSTRACT FROM AUTHOR]

Chronic illness not only affects the life of those suffering from Huntington's disease but also threatens the quality of life (QOL) of their spouses. In this study, we focus on Huntington's disease (HD). The impact of HD on the QOL of spouses has been hardly studied from a behavioral medicine or health psychology perspective. We hypothesize that spouses' illness perceptions and coping mechanisms will contribute significantly to the prediction of their QOL. Illness perceptions, coping mechanisms, and the QOL of 90 spouses of patients with HD were assessed by means of the Illness Perception Questionnaire, the COPE, and the Medical Outcome Study 36-item Short Form Health Survey, respectively. After controlling for demographic and illness-related variables, coping mechanisms explained a significant amount of variance of spouses' role functioning. Given our results, more empirical and longitudinal research is justified on coping mechanisms and illness perceptions of spouses living with Huntington's disease. [ABSTRACT FROM AUTHOR]

Background and Objectives: The total functioning capacity (TFC) assessment has been integral to Huntington's disease (HD) research and clinical trials, measuring disease stage and progression. This study investigates the natural progression of function in HD, focusing on changes in TFC scores related to age and CAG-repeat length, and evaluates TFC's strengths and weaknesses in longitudinal studies., Methods: Using Enroll-HD platform's clinical dataset version 5, including Registry-3, we analysed data from 21,079 participants, with 16,083 having an expanded CAG repeat. Our final analysis encompassed 15,527 patients and 52,457 visits, with TFC scores ranging from 0 to 13., Results: Alluvial charts show that most individuals maintain maximum functional capacity over time. 3505 individuals experienced change in TFC scores, over the subsequent 4 years, 2224 (64.1%) experienced declining TFC scores, while 661 (18.6%) showed improvement within a year. The remaining 17.3% exhibited stable TFC scores. Age-related changes followed a specific sequence: occupation, household chores/finances, daily living, and care. Longer CAG-repeat lengths were linked to earlier functional decline, with some geographic regions showing earlier losses in specific domains. Reduced penetrance CAG-repeat groups exhibited different trajectories from full penetrance HD participants., Discussion: When we focus on those who experienced a change in TFC score, the number of HD patients with regained functional capacity is substantial, even considering interrater variability, which may influence outcome assessments in clinical trials. The TFC effectively reflects changes in functional domains as intended. Analysis of the reduced penetrance group suggests potential selection biases in seeking medical attention earlier and for reasons unrelated to HD., Competing Interests: Declarations. Conflicts of Interest: O.M. Dekker is Deputy Editor European Journal of Endocrinology. R.A.C. Roos is member of the DSMB uniQure CT-AMT 130, DSMB Enroll-HD. Susanne T. de Bot is a member of the HD Expert Advisory Panel for the PTC518 phase 3 program (PTC Therapeutics). Ethical Standard Statement: This study was conducted in compliance with the ethical standards outlined in the Declaration of Helsinki. All sites obtained and maintained local ethical approval. All participants provided informed consent prior to participation in the study, and their confidentiality and privacy were maintained throughout., (© 2024. The Author(s).)

Background: Proper medication reconciliation (= comparing the accuracy of patient-reported medication use with pharmacy records) could prevent potentially dangerous situations such as drug-drug interactions and hospitalization. This is particularly important when patients rely on multiple medications, such as in neurodegenerative disorders like Huntington's Disease (HD). Currently, it is unknown how often medication discrepancies occur in HD patients and which factors contribute to the discrepancies., Objective: Identify prognostic factors of medication discrepancies in HD, using patient-reported medication use and local pharmacy records., Methods: With 134 pre- and manifest HD patients, we performed a multivariable logistic regression analysis with medication discrepancy as dependent variable (pharmacy records as reference value) and sex, CAP score, disease status (pre- or manifest HD), number of concomitant medications taken, presence of an informal caregiver, Unified Huntington's Disease Rating Scale-Total Functioning Capacity, unified cognitive Z-score and Problem Behaviors Assessment-short characteristic scores for depression, anxiety, and apathy as independent variables., Results: Medication discrepancies were reported frequently, both in premanifest (43.2%) and manifest HD subjects (36.7%). Impaired cognition significantly predicted medication discrepancies (beta = -0.688, SE 0.27, p = 0.011). All other variables were non-significant., Conclusions: Regardless of HD disease status and stage, patient self-reported medication use is not a reliable source, especially in those with impaired cognitive function. The presence of an informal caregiver and the absence of polypharmacy, depression, anxiety and apathy do not influence self-reported medication accuracy. Objective verification of medication use with HD patients' local pharmacy is recommended., Trial Registration Number: ICTRP-NL-OMON55123, HD-med, registered 26-Nov-2019., Competing Interests: Declarations. Conflict of interest: This research was supported by private HD community donations. We received no funding from commercial or not-for-profit parties. HD-MED is an investigator-initiated study set up by the Department of Neurology and Department of Clinical Pharmacy and Toxicology of the Leiden University Medical Center. The authors declare that there are no conflicts of interest relevant to this work. Ethics approval, and consent to participate and publish: All participants in the HD-MED and ENROLL-HD study gave written informed consent to participate in the study and have their data published in international journals. The HD-MED study is approved by the medical research ethics committee Leiden Den Haag Delft under number NL70391.058.19 and is registered in the International Clinical Trials Registry Platform under number NL-OMON55123. The HD-med study is in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All sites participating in the ENROLL-HD study have obtained local ethical approval. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines., (© 2024. The Author(s).)

Background: Huntington's Disease is a rare neurodegenerative disorder in which appropriate medication management is essential. While many medications are prescribed based on expert knowledge, overviews of actual medication use in HD are sparse., Objectives: We provide a detailed overview of medication use and associated indications across HD disease stages, considering sex and regional differences., Methods: Data from the largest observational HD study, ENROLL-HD, were used. We created HD-related medication and indication classes to identify medication trends in manifest, premanifest and control subjects. We studied medication use in adult, childhood- and adolescent-onset HD, incorporating disease stage (including phenoconverters), sex and regional differences., Results: In 8546 manifest HD patients, 84.6% used medication (any type), with the average number of medications per user rising from 2.5 in premanifest HD to 5.2 in end stage disease. Antipsychotics (29.2%), SSRIs (27.5%) and painkillers (21.8%) were most often used. Medication use varied with disease progression. Several differences were observed between the sexes, and notably between Europe and Northern America as well. Medication use increased after phenoconversion (from 64.8% to 70.6%, P < 0.05), with the largest difference in antipsychotic use (4.4%-7.8%, P < 0.05). Medication patterns were different in childhood-onset HD, with no use of painkillers, less use of anti-chorea and antidepressant drugs, and more for aggression and irritability., Conclusions: Medication use in HD increases with disease progression, with varying types of medications prescribed based on disease stage, sex, and region of living. Recognizing these medication trends is vital for further personalized HD management., (© 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Juvenile-onset Huntington's disease (JHD) represents 1-5% of Huntington's disease (HD) patients, with onset before the age of 21. Pediatric HD (PHD) relates to a proportion of JHD patients that is still under 18 years of age. So far, both populations have been excluded from interventional trials., Objective: Describe the prevalence and incidence of JHD and PHD in the Netherlands and explore their ability to participate in interventional trials., Methods: The prevalence and incidence of PHD and JHD patients in the Netherlands were analyzed. In addition, we explored proportions of JHD patients diagnosed at pediatric versus adult age, their diagnostic delay, and functional and modelled (CAP100) disease stage in JHD and adult-onset HD patients at diagnosis., Results: The prevalence of JHD and PHD relative to the total manifest HD population in January 2024 was between 0.84-1.25% and 0.09-0.14% respectively. The mean incidence of JHD patients being diagnosed was between 0.85-1.28 per 1000 patient years and of PHD 0.14 per 1.000.000 under-aged person years. 55% of JHD cases received a clinical diagnosis on adult age. At diagnosis, the majority of JHD patients was functionally compromised and adolescent-onset JHD patients were significantly less independent compared to adult-onset HD patients., Conclusions: In the Netherlands, the epidemiology of JHD and PHD is lower than previously suggested. More than half of JHD cases are not eligible for trials in the PHD population. Furthermore, higher functional dependency in JHD patients influences their ability to participate in trials. Lastly, certain UHDRS functional assessments and the CAP100 score do not seem appropriate for this particular group.

Cortical cell loss is a core feature of Huntington's disease (HD), beginning many years before clinical motor diagnosis, during the premanifest stage. However, it is unclear how genetic topography relates to cortical cell loss. Here, we explore the biological processes and cell types underlying this relationship and validate these using cell-specific post-mortem data. Eighty premanifest participants on average 15 years from disease onset and 71 controls were included. Using volumetric and diffusion MRI we extracted HD-specific whole brain maps where lower grey matter volume and higher grey matter mean diffusivity, relative to controls, were used as proxies of cortical cell loss. These maps were combined with gene expression data from the Allen Human Brain Atlas (AHBA) to investigate the biological processes relating genetic topography and cortical cell loss. Cortical cell loss was positively correlated with the expression of developmental genes (i.e. higher expression correlated with greater atrophy and increased diffusivity) and negatively correlated with the expression of synaptic and metabolic genes that have been implicated in neurodegeneration. These findings were consistent for diffusion MRI and volumetric HD-specific brain maps. As wild-type huntingtin is known to play a role in neurodevelopment, we explored the association between wild-type huntingtin (HTT) expression and developmental gene expression across the AHBA. Co-expression network analyses in 134 human brains free of neurodegenerative disorders were also performed. HTT expression was correlated with the expression of genes involved in neurodevelopment while co-expression network analyses also revealed that HTT expression was associated with developmental biological processes. Expression weighted cell-type enrichment (EWCE) analyses were used to explore which specific cell types were associated with HD cortical cell loss and these associations were validated using cell specific single nucleus RNAseq (snRNAseq) data from post-mortem HD brains. The developmental transcriptomic profile of cortical cell loss in preHD was enriched in astrocytes and endothelial cells, while the neurodegenerative transcriptomic profile was enriched for neuronal and microglial cells. Astrocyte-specific genes differentially expressed in HD post-mortem brains relative to controls using snRNAseq were enriched in the developmental transcriptomic profile, while neuronal and microglial-specific genes were enriched in the neurodegenerative transcriptomic profile. Our findings suggest that cortical cell loss in preHD may arise from dual pathological processes, emerging as a consequence of neurodevelopmental changes, at the beginning of life, followed by neurodegeneration in adulthood, targeting areas with reduced expression of synaptic and metabolic genes. These events result in age-related cell death across multiple brain cell types., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

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., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Huntington's Disease (HD) is a rare, neurodegenerative disorder characterized by chorea, cognitive decline, and behavioral changes. Despite wide clinical use since the mid-1980s, tiapride was recently withdrawn from the Dutch market without rationale. Although alternatives are available, many patients experienced dysregulation after this unwanted change. We provide insight into the impact of sudden tiapride withdrawal by reviewing medical records of HD patients who were using tiapride at the time of withdrawal. In addition, we performed a systematic search in five databases on tiapride efficacy and its safety profile in HD. Original research and expert opinions were included. In our patient group on tiapride, 50% required tiapride import from abroad. Regarding the review, 12 articles on original datasets and three expert opinions were included. The majority of studies showed an improvement in chorea while patients were on tiapride. Due to limited sample sizes, not all studies performed statistical tests on their results. Fifty percent of clinical experts prefer tiapride as initial chorea monotherapy, especially when comorbid behavioral symptoms are present. Side effects are often rare and mild. No safety concerns were reported. In conclusion, tiapride is almost irreplaceable for some patients and is an effective and safe chorea treatment in HD.

Huntington's disease (HD) is an inherited neurodegenerative disease. People at risk for HD can choose to get predictive testing years before the clinical onset. HD is characterized by motor, cognitive and psychiatric symptoms and has a mean age at onset between 30 and 50 years, an age at which people are usually still working. This systematic review focuses on summarizing which disease-specific characteristics influence employment and working capacity in HD. Twenty-three studies were identified and showed that while employment and working capacity in HD are negatively influenced by cognitive decline and motor impairments, apathy already plays a role in the prodromal stage. Moreover, the influence of HD transcends the clinical manifestation of the disease, as some people at risk are already experiencing the impact of HD on employment through fear of or actual genetic discrimination. Employment and working capacity are not influenced by predictive testing for HD in and of itself., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Huntington disease is an autosomal dominant inherited brain disorder that typically becomes manifest in adulthood. Juvenile-onset Huntington disease refers to approximately 5% of patients with symptom onset before the age of 21 years. The causal factor is a pathologically expanded CAG repeat in the Huntingtin gene. Age at onset is inversely correlated with CAG repeat length. Juvenile-onset patients have distinct symptoms and signs with more severe pathology of involved brain structures in comparison with disease onset in adulthood. The aim of this review is to compare clinical and pathological features in juvenile- and adult-onset Huntington disease and to explore which processes potentially contribute to the observed differences. A specific focus is placed on molecular mechanisms of mutant huntingtin in early neurodevelopment and the interaction of a neurodegenerative disease and postnatal brain maturation. The importance of a better understanding of pathophysiological differences between juvenile- and adult-onset Huntington disease lies in development and implementation of new therapeutic strategies. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Objectives: To explore the prevalence of dysphagia and fear of choking in patients with Huntington's disease (HD) as well as preventive measures, both those applied and those not included in managing dysphagia. Also, to investigate related problems encountered by their formal and informal caregivers., Design: A multi-center observational cross-sectional study., Setting and Participants: 158 HD patients, recruited from six Dutch nursing homes specialized in HD, and their formal and informal caregivers., Measurements: Patients were assessed by means of questionnaires enquiring about dysphagia, fear of choking and measures to manage dysphagia. Also, questionnaires were administered about awareness of dysphagia symptoms, cognition and anxiety. Because we expected individuals with greater care dependency to have a higher severity of dysphagia, we distinguished between a care-independent and a care-dependent group of HD patients., Results: In the total group, 90.5% of HD patients had one or more dysphagia symptoms. The prevalence of FoC in HD patients and the formal and informal caregivers' fears about choking in HD patients was 45.7%, 19.0% and 59.5%, respectively, for care-independent patients and 58.7%, 50.1% and 77.5% for care-dependent patients. The score on the Huntington's Disease Dysphagia Scale was a predictor for fear of FoC in care-independent patients. Speech-language therapy, supervision during eating and drinking and adaptation of food and drink consistency were the most frequently applied measures to manage dysphagia, a combination was used in most HD patients., Conclusions: In HD patients, the prevalence of dysphagia is high and fear of choking is common among both patients and caregivers. A more severe degree of dysphagia is a predictor of FoC in care-independent HD patients. A combination of measures was used to manage dysphagia in most HD patients., Competing Interests: The authors have no conflict of interest to report.

Introduction: Pain could be an unknown non-motor symptom in Huntington's Disease (HD). The aim is therefore, to study the prevalence of pain interference, painful conditions and analgesic use across the different stages of HD and compare these levels to non-HD gene mutation carriers., Methods: A cross-sectional analysis of the Enroll-HD study was conducted in premanifest, manifest HD gene mutation carriers (n = 3989 and n = 7,485, respectively) and in non-HD gene mutation carriers (n = 3719). To investigate group differences, multivariable logistic regression analysis was performed with pairwise comparisons., Results: In the HD mutation carriers, the overall prevalence of pain interference was 34% (95% CI 31%-35%), of painful conditions 17% (95% CI 15%-19%) and analgesic use 13% (95% CI 11%-15%). Compared to non-mutation carriers, the prevalence of pain interference was significantly higher in the middle stage of HD (33% [95% CI 31%-35%] vs 42% [95% CI 39%-45%], P = 0,02), whereas the prevalence of painful conditions was significant lower in the late and middle stage of HD (17% [95% CI 16%-18%] vs 12% [95% CI 10%-14%], 15% [95% CI 13%-17%], P < 0,01]. No significant group difference was present in analgesic use., Conclusions: The prevalence of pain interference increases as HD progresses, however, the prevalence of painful conditions and analgesics do not increase accordingly. Further studies are necessary to investigate the aetiology of pain in HD and the risk for undertreatment of pain., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: Huntington's disease (HD) is a neurodegenerative disease with cognitive, motor and psychiatric symptoms. Toxic accumulation of misfolded mutant huntingtin protein induces mitochondrial dysfunction, leading to a bioenergetic insufficiency in neuronal and muscle cells. We evaluated the safety, pharmacokinetics and pharmacodynamics of SBT-020, a novel compound to improve mitochondrial function, in a 2-part study in early stage HD patients., Methods: Part 1 consisted of 7-day multiple ascending dose study to select the highest tolerable dose for Part 2, a 28-day multiple dose study. Mitochondrial function was measured in the visual cortex and calf muscle, using phosphorous magnetic resonance spectroscopy, and in circulating peripheral blood mononuclear cells., Results: Treatment-emergent adverse events were mild and more present in the SBT-020 group. Injection site reactions occurred in 91% in Part 1 and 97% in Part 2. Mitochondrial function in calf muscle, peripheral blood mononuclear cells or visual cortex was not changed overall due to treatment with SBT-020. In a posthoc analysis, patients with a higher degree of mitochondrial dysfunction (below the median [∆Ψ m < 3412 and τPCr > 42.5 s]) showed more improvement than patients with a relatively lower level of mitochondrial dysfunction., Conclusion: SBT-020 was safe at all doses, but no significant differences in any of the pharmacodynamic measurements between the treatment groups and placebo group could be demonstrated. The data suggest that the better than expected mitochondrial function in our patient population at baseline might explain the lack of effect of SBT-020., (© 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: The composite Unified Huntington's Disease Rating Scale (cUHDRS) is a multidimensional measure of progression in Huntington's disease (HD) being used as a primary outcome in clinical trials investigating potentially disease-modifying huntingtin-lowering therapies., Objective: Evaluating volumetric and structural connectivity correlates of the cUHDRS., Methods: One hundred and nineteen premanifest and 119 early-HD participants were included. Gray and white matter (WM) volumes were correlated with cUHDRS cross-sectionally and longitudinally using voxel-based morphometry. Correlations between baseline fractional anisotropy (FA); mean, radial, and axial diffusivity; and baseline cUHDRS were examined using tract-based spatial statistics., Results: Worse performance in the cUHDRS over time correlated with longitudinal volume decreases in the occipito-parietal cortex and centrum semiovale, whereas lower baseline scores correlated with decreased volume in the basal ganglia and surrounding WM. Lower cUHDRS scores were also associated with reduced FA and increased diffusivity at baseline., Conclusion: The cUHDRS correlates with imaging biomarkers and tracks atrophy progression in HD supporting its biological relevance. © 2021 International Parkinson and Movement Disorder Society., (© 2021 International Parkinson and Movement Disorder Society.)