Time will tell: Decision making in premanifest and manifest Huntington’s disease

Heim, Beatrice; Peball, Marina; Saft, Carsten; Hein, Sarah Maria von; Ellmerer, Philipp; Piater, Johanna Maria; Seppi, Klaus

doi:10.1002/brb3.1843

Cited by 9 publications

(11 citation statements)

References 53 publications

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“…Focusing on the large cohort of premanifest participants, we investigated in these patients, formally without a clinical diagnosis of HD, more motoric, functional, cognitive, and psychiatric impairments if compared to genotype negative, and, in some parts, if compared to family controls. These findings go along with other research describing prodromal phases of HD, before the onset of distinct motoric symptoms (defined as diagnostic confidence level 4) and also go along with earlier observed neurocognitive, neuropsychiatric, biomarker, and structural MRI changes with brain atrophy in premanifest HD patients [ 40 , 41 , 42 , 43 , 44 , 45 ] Recently, CSF neurofilament light protein (NfL) was identified as a potential biomarker and is elevated far before the onset in pre-HD as a sensitive measure for neurodegenerative processes, starting decades before clinical onset [ 46 ]. As a limitation, no CSF measures or neuro-imaging data were available within the investigated cohorts, so neurobiological correlates could not be identified.…”

Section: Discussionsupporting

confidence: 86%

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

Saft

2021

Brain Sciences

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Background: In addition to the effects on patients suffering from motor-manifest Huntington’s disease (HD), this fatal disease is devasting to people who are at risk, premanifest mutation-carriers, and especially to whole families. There is a huge burden on people in the environment of affected HD patients, and a need for further research to identify at-risk caregivers. The aim of our research was to investigate a large cohort of family members, in comparison with genotype negative and premanifest HD in order to evaluate particular cohorts more closely. Methods: We used the ENROLL-HD global registry study to compare motoric, cognitive, functional, and psychiatric manifestation in family members, premanifest HD, and genotype negative participant as controls. Cross-sectional data were analyzed using ANCOVA-analyses in IBM SPSS Statistics V.28. Results: Of N = 21,116 participants from the global registry study, n = 5174 participants had a premanifest motor-phenotype, n = 2358 were identified as family controls, and n = 2640 with a negative HD genotype. Analysis of variance revealed more motoric, cognitive, and psychiatric impairments in premanifest HD (all p < 0.001). Self-reported psychiatric assessments revealed a significantly higher score for depression in family controls (p < 0.001) when compared to genotype negative (p < 0.001) and premanifest HD patients (p < 0.05). Family controls had significantly less cognitive capacities within the cognitive test battery when compared to genotype negative participants. Conclusions: Within the largest cohort of HD patients and families, several impairments of motoric, functional, cognitive, and psychiatric components can be confirmed in a large cohort of premanifest HD, potentially due to prodromal HD pathology. HD family controls suffered from higher self-reported depression and less cognitive capacities, which were potentially due to loaded or stressful situations. This research aims to sensitize investigators to be aware of caregiver burdens caused by HD and encourage support with socio-medical care and targeted psychological interventions. In particular, further surveys and variables are necessary in order to implement them within the database so as to identify at-risk caregivers.

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Section: Discussionsupporting

confidence: 86%

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

Saft

2021

Brain Sciences

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“…In line with this, deficits in emotion recognition and emotion recognition of body language is also reduced in HD patients [10, 14] and correlated with the severity of motor symptoms [14]. Given these impairments of emotion recognition as well as difficulties understanding social norms, the high prevalence of irritability and aggression in HD [15], the known widespread brain atrophy [16], and the impairment in decision-making [4], we speculated that our manifest HD cohort would perform worse than healthy control (HC), i.e., punish more often than HC. Hence, we wanted to assess whether extensive punishment is part of the neuropsychological profile of patients with manifest HD using a costly punishment task where participants were asked in fair and unfair rounds to punish a virtual counterpart.…”

Section: Introductionmentioning

confidence: 98%

“…Neuropsychiatric abnormalities can often precede motor symptoms [1][2][3] and can be more debilitating for HD patients and their families. Several studies found impairment in decision-making [4], theory of mind [5], overcoming stimulus-response incompatibility and prepulse inhibition [6], obsessive-compulsive behaviours [7], impairment in social perception [8], and emotion processing [9,10] in HD patients.…”

Section: Introductionmentioning

confidence: 99%

Tit for Tat: Costly Punishment in Manifest Huntington’s Disease

et al. 2021

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Objective: We aimed to investigate costly punishment in patients with HD. Background: Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease with motor, cognitive, and psychiatric symptoms. As neuropsychiatric abnormalities often precede motor symptoms, we wanted to assess whether costly punishment is part of the neuropsychological profile of patients with HD. Methods: A total of 40 non demented subjects were prospectively enrolled in this study with a between-subject design comparing manifest HD patients (n=18) to healthy controls (HC; n=22). All participants performed eight rounds of a costly punishment task, in which money was shared unevenly in 5 rounds or in a fair manner in the remaining three rounds. Participants then had to decide whether they wanted to punish the trustee. Furthermore, all participants underwent neuropsychological background tasks. Results: HD patients performed worse in the neuropsychological background tests compared to HC (all p-values<0.05). Moreover, HD patients punished more often in fair (Wald x2=5.03, p=0.025) but not in unfair rounds (Wald x2=1.63, p=0.202). Conclusions: Our results demonstrate increased costly punishment during fair conditions in HD patients. Whether this behaviour is due to a lack of recognition of social norms, an impairment in top-down inhibition, or an effect of anti-dopaminergic medication remains unclear.

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“…Nevertheless, these are preliminary data of a small sample size only tested by a subset of olfactory functioning. Our results provide indication that apart from early behavioral and cognitive changes in HD carriers [21], olfactory dysfunction could present another nonmotor symptom of HD present in very early disease stages and that further longitudinal studies are needed.…”

Section: Discussionmentioning

confidence: 77%

Extending the Spectrum of Nonmotor Symptoms with Olfaction in Premotor Huntington’s Disease: A Pilot Study

Heim¹,

Valent²,

Carbone³

et al. 2020

Neurodegener Dis

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Objective:The aim of this pilot study was to investigate change of olfactory functions in Huntington's disease (HD). Background: HD is a neurodegenerative disease characterized by motor, cognitive, and behavioral abnormalities. There are several studies reporting olfactory dysfunction in manifest and some studies in premanifest HD carriers, and a recent neuropathological study demonstrated HD-specific protein aggregation in the anterior olfactory nucleus in HD patients. In this study, we wanted to assess olfactory functions as a possible early nonmotor symptom of HD mutation carriers without disease-specific motor symptoms and HD patients. Methods: All participants had genetic confirmed HD and were prospectively recruited during their routine control in a specialized outpatient clinic of the Medical University of Innsbruck, Department of Neurology, Austria. Healthy controls (HCs) were caregivers from patients. They were only included if they were younger than 70 years, scored more than 24/30 points on the Mini Mental State Ex-amination, and had no other disease compromising olfactory function. Furthermore, all participants were tested on the Sniffin' sticks 16-items identification test. Results: We included 23 patients with manifest HD, 13 HD mutation carriers, and 19 HCs. Mutation carriers showed significant impaired odor identification compared to HCs (p < 0.001), as well as Huntington's patients compared with both mutation carriers (p = 0.003) and HCs (p < 0.001). Conclusions: The results of this pilot study suggest that olfactory dysfunction may be an early nonmotor symptom of HD and could be a potential marker to assess disease progression.

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Time will tell: Decision making in premanifest and manifest Huntington’s disease

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 9 publications

References 53 publications

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

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

Tit for Tat: Costly Punishment in Manifest Huntington’s Disease

Extending the Spectrum of Nonmotor Symptoms with Olfaction in Premotor Huntington’s Disease: A Pilot Study

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