Another Perspective on Huntington’s Disease: Disease Burden in Family Members and Pre-Manifest HD When Compared to Genotype-Negative Participants from ENROLL-HD

Achenbach, Jannis; Saft, Carsten

doi:10.3390/brainsci11121621

Cited by 11 publications

(8 citation statements)

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“…Importantly, significant differences in symptom frequency between pwHD (manifest and premanifest) and noncarriers (family controls and genotype‐negative) were only found for three indices of the PBA‐s, and not for the remaining eight (depression, suicidal ideation, anxiety, irritability, aggression, perseveration, paranoia, and hallucinations). This supports previous findings that a degree of psychological distress in various forms is shared between carriers and noncarriers across HD‐affected families (Achenbach & Saft, 2021 ; Maltby et al., 2021 ). Descriptions of psychosocial contributions to HD‐related distress may support this interpretation, as both carriers and noncarriers may experience intense anxiety and distress relating to changed familial narratives, disrupted interpersonal dynamics, grief, and lost plans for the future (Berrios et al., 2002 ; Brouwer‐DudokdeWit et al., 2002 ; Tibben et al., 1997 ; Yu et al., 2019 ).…”

Section: Discussionsupporting

confidence: 91%

“…This supports previous findings that a degree of psychological distress in various forms is shared between carriers and noncarriers across HD-affected families (Achenbach & Saft, 2021;Maltby et al, 2021). Descriptions of psychosocial contributions to HD-related distress may support this interpretation, as both carriers and noncarriers may experience intense anxiety and distress relating to changed familial narratives, disrupted interpersonal dynamics, grief, and lost plans for the future (Berrios et al, 2002;Brouwer-DudokdeWit et al, 2002;Tibben et al, 1997;Yu et al, 2019).…”

Section: Discussionsupporting

confidence: 88%

“…These include cognitive changes in memory, executive function, information processing, and emotional lability, and mental health symptoms such as depression, anxiety, irritability/anger, obsessive–compulsive behaviors, apathy, perseveration, and (less commonly) psychosis (Rickards et al., 2011 ; van Duijn, 2017 ; van Duijn et al., 2014 , 2007 ). Although motor changes are viewed as the most characteristic symptoms of HD, both people with HD (pwHD) and their families report that mental health is a primary issue in care (Mahmood et al., 2022 ; Smith et al., 2015 ), and mental distress has been demonstrated throughout HD families, including genetically unaffected individuals (Achenbach & Saft, 2021 ; Maltby et al., 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Mental health symptoms among those affected by Huntington's disease: A cross‐sectional study

et al. 2023

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Background Although cognitive and motor symptoms of Huntington's disease (HD) are associated with disease progression, the underlying causes of psychological symptoms are not as clearly understood. Recent evidence suggests that some mental health difficulties experienced by people with HD are shared by noncarriers within HD families. Accordingly, there is a need to evaluate potential systemic contributors to HD mental distress, to support meaningful interventions for psychological symptoms in people with HD and affected families. Method We used short‐form Problem Behaviors Assessment mental health symptom data from the international Enroll‐HD data set to characterize mental health symptoms across eight HD groups: Stages 1–5, premanifest and genotype‐negative individuals, and family controls ( n = 8567) using chi‐square analysis with post hoc comparisons. Results We identified that people with later‐stage HD (Stages 2–5) had significantly higher apathy, obsessive–compulsiveness, and (from Stage 3) disorientation than the remaining groups at a medium effect size, and that these findings largely held across three measure administrations over time. Conclusions These findings highlight the critical symptoms in manifest HD from Stage 2 onward, but also demonstrate that crucial symptoms such as depression, anxiety, and irritability are present across HD‐affected groups (including noncarriers of the gene expansion). The outcomes highlight a need for specific clinical management of later‐stage HD psychological symptoms, and for systemic support across affected families.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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Mental health symptoms among those affected by Huntington's disease: A cross‐sectional study

et al. 2023

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“…Aschenbach et al presented a cross-sectional study of the global enrollment HD registry [ 23 ]. In this huge cohort, the authors compared HD patients, premanifest mutation carriers, HD negative family members, and genetic negative control participants.…”

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confidence: 99%

Caregiver Burden in Movement Disorders and Neurodegenerative Diseases: Editorial

Klietz

2022

Brain Sciences

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“…Among the wide range of neurodegenerative diseases, neurological motor disorders (NMDs) such as Parkinson's disease (PD) and Huntington's disease (HD) have increased their prevalence, having a negative impact on public health as the associated financial burden will continue to increase (Ou et al, 2021 ). Moreover, NMDs and other neurodegenerative diseases are not only a freight for the patients and public health systems, but also negatively impact the quality of life of caregivers, which are usually patient's family members (Achenbach and Saft, 2021 ; Rosqvist et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Small molecules to perform big roles: The search for Parkinson's and Huntington's disease therapeutics

et al. 2023

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Neurological motor disorders (NMDs) such as Parkinson's disease and Huntington's disease are characterized by the accumulation and aggregation of misfolded proteins that trigger cell death of specific neuronal populations in the central nervous system. Differential neuronal loss initiates the impaired motor control and cognitive function in the affected patients. Although major advances have been carried out to understand the molecular basis of these diseases, to date there are no treatments that can prevent, cure, or significantly delay the progression of the disease. In this context, strategies such as gene editing, cellular therapy, among others, have gained attention as they effectively reduce the load of toxic protein aggregates in different models of neurodegeneration. Nevertheless, these strategies are expensive and difficult to deliver into the patients' nervous system. Thus, small molecules and natural products that reduce protein aggregation levels are highly sought after. Numerous drug discovery efforts have analyzed large libraries of synthetic compounds for the treatment of different NMDs, with a few candidates reaching clinical trials. Moreover, the recognition of new druggable targets for NMDs has allowed the discovery of new small molecules that have demonstrated their efficacy in pre-clinical studies. It is also important to recognize the contribution of natural products to the discovery of new candidates that can prevent or cure NMDs. Additionally, the repurposing of drugs for the treatment of NMDs has gained huge attention as they have already been through clinical trials confirming their safety in humans, which can accelerate the development of new treatment. In this review, we will focus on the new advances in the discovery of small molecules for the treatment of Parkinson's and Huntington's disease. We will begin by discussing the available pharmacological treatments to modulate the progression of neurodegeneration and to alleviate the motor symptoms in these diseases. Then, we will analyze those small molecules that have reached or are currently under clinical trials, including natural products and repurposed drugs.

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Another Perspective on Huntington’s Disease: Disease Burden in Family Members and Pre-Manifest HD When Compared to Genotype-Negative Participants from ENROLL-HD

Cited by 11 publications

References 58 publications

Mental health symptoms among those affected by Huntington's disease: A cross‐sectional study

Mental health symptoms among those affected by Huntington's disease: A cross‐sectional study

Caregiver Burden in Movement Disorders and Neurodegenerative Diseases: Editorial

Small molecules to perform big roles: The search for Parkinson's and Huntington's disease therapeutics

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