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Background: Huntington's disease (HD) is a rare, neurodegenerative disease and its complex motor, cognitive and psychiatric symptoms exert a lifelong clinical burden on both patients and their families. Objective: To describe the clinical burden and natural history of HD. Methods: This longitudinal cohort study used data from the linked Swedish national registries to describe the occurrence of comorbidities (acute and chronic), symptomatic treatments and mortality in an incident cohort of individuals who either received the first diagnosis of HD above (adult onset HD; AoHD) or below (juvenile-onset HD; JoHD) 20 years of age, compared with a matched cohort without HD from the general population. Disease burden of all individuals alive in Sweden was described during a single calendar year (2018), including the occurrence of key symptoms, treatments and hospitalizations. Results: The prevalence of HD in 2018 was approximately 10.2 per 100,000. Of 1492 individuals with a diagnosis of HD during 2002 and 2018, 1447 had AoHD and 45 had JoHD. Individuals with AoHD suffered a higher incidence of obsessive–compulsive disorder, acute psychotic episodes, pneumonia, constipation and fractures compared with matched controls. Individuals with JoHD had higher incidence rates of epilepsy, constipation and acute respiratory symptoms. Median time to all-cause mortality in AoHD was 12.1 years from diagnosis. Patients alive with HD in Sweden in 2018 displayed a pattern of increased clinical burden for a number of years since diagnosis. Conclusions: This study demonstrates the significant and progressive clinical burden in individuals with HD and presents novel insights into the natural history of JoHD. [ABSTRACT FROM AUTHOR]

Objectives: Huntington's disease (HD) is a progressive neuropsychiatric disease characterized by involuntary movements and behavioural symptoms. This study aimed to explore the association between the level of Sense of Coherence (SOC) and health problems, and psychological distress factors in partners to HD affected persons and their need of support. Materials & Methods: A cross‐sectional, descriptive, correlational design was used. Data was generated from 94 HD partners from almost all networks, outpatient clinics and nursing homes specialized in HD across Sweden. HD partners filled out questionnaires with scales measuring SOC, health problems, psychological distress factors and the Total Functional Capacity Scale (TFC). Non‐parametric analysis was used to analyse group differences. Results: Huntington's disease partners with a lower level of SOC experienced more health problems than those with a higher level. Health problems among HD partners were most common among HD affected in TFC stage 3, indicating that the partners need most support during this period. Lower level of SOC was associated with loneliness in the relationship; less possibilities to socialize with friends; worries about the future as well as being subjected to physical aggression. The experience of physical aggression from the HD affected person was common (44.7%) and 28.6% of the partners expressed worries about being subjected to physical aggression. Conclusion: Our findings suggest that knowledge about the partners' SOC score may be a helpful indicator identifying HD partners who are more vulnerable and need additional help caring for the person with HD and can be a complementary tool in assessment protocols. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a hereditary neurodegenerative disease, currently lacking disease-modifying treatments. Biomarkers are needed for objective assessment of disease progression. Evidence supports both complex protein aggregation and astrocyte activation in HD. This study assesses the 42 amino acid long amyloid beta (Aβ42) and glial fibrillary acidic protein (GFAP) as potential biomarkers in the cerebrospinal fluid (CSF) of HD mutation carriers. CSF from participants was obtained from three sites in Sweden. Clinical symptoms were graded with the composite Unified Huntington's disease rating scale (cUHDRS). Protein concentrations were measured using ELISA. Pearson correlations were calculated to assess disease progression association. Results were adjusted for age and collection site. The study enrolled 28 manifest HD patients (ManHD), 13 premanifest HD gene-expansion carriers (PreHD) and 20 controls. Aβ42 levels did not differ between groups and there was no correlation with measures of disease progression. GFAP concentration was higher in ManHD (424 ng/l, SD 253) compared with both PreHD (266 ng/l, SD 92.4) and controls (208 ng/l, SD 83.7). GFAP correlated with both cUHDRS (r = −0.77, p < 0.001), and 5-year risk of disease onset (r = 0.70, p = 0.008). We provide evidence that indicates CSF Aβ42 has limited potential as a biomarker for HD. GFAP is a potential biomarker of progression in HD. Validation in larger cohorts measuring GFAP in blood and CSF would be of interest. • CSF Aβ42 is not associated with disease stage or clinical symptoms. • GFAP is increased in CSF of HD patients and increases already as the time to disease-onset abates. • GFAP levels are more closely associated to disease phenotype than CAG repeats and age combined. [ABSTRACT FROM AUTHOR]

Modernity has meant a cultural and social differentiation within the western society, which, according to Jürgen Habermas’ theory on communication, can be seen as a division between different forms of actions that takes place in different realms of the society. By combining Habermas’ notions of lifeworld and system with Arthur Frank’s analysis of stories as a way to experience illness, the article performs a cultural analysis of the meeting between families involved in caregiving in relation to Huntington’s disease and the Swedish welfare system. The ethnographic material shows how caregiving is given meaning through communicative action and illness stories, which are broken up by an instrumental legal discourse employed by the welfare system. This confrontation between communicative and instrumental action breeds alienation towards the state and the welfare system among the affected families. However, the families are able to empower themselves and confront the system through a hybrid form of action, which combines communicative and instrumental action. As such this hybridity, and the space that opens up on the basis of this hybridity, constitutes an important space within the modern society. [ABSTRACT FROM AUTHOR]

Purpose: The influence of the cytochrome P450 enzyme CYP2D6 in the metabolism of the novel dopaminergic stabilizer pridopidine was investigated in healthy Swedish Caucasians. Methods: Six extensive metabolizers (EM) and six poor metabolizers (PM) of debrisoquine were given a single oral dose of pridopidine (EM, 50 mg; PM, 25 mg). Results: The mean total plasma clearance of pridopidine was 541 and 138 mL/min in EM and PM, respectively ( p = 0.003), and was slightly higher in PM than the mean renal plasma clearance (105 mL/min; p = 0.11). The mean plasma area under the time-concentration curve between time zero and 32 h (AUC) of the N-depropyl metabolite ACR30 was higher in EM than in PM (1,377 vs. 61 nmol h/mL, respectively; p < 0.001). The urinary excretion of pridopidine + ACR30 was high in both EM (85 %) and PM (78 %). The dose-adjusted peak concentration (C) was not statistically different in EM and PM; consequently, the oral absorption of pridopidine was close to complete. Conclusions: Following a single dose of pridopidine, the drug is N-depropylated by CYP2D6 in EM, while in PM the most important elimination pathway is renal glomerular filtration. Results of studies examining the effects of multiple repeat dosing suggest that the CYP2D6 enzyme is at least partly inactivated by pridopidine. [ABSTRACT FROM AUTHOR]

Background: Huntington's disease not only affects motor speech control, but also may have an impact on the ability to produce and understand language in communication. Aims: The ability to comprehend basic and complex discourse was investigated in three different stages of Huntington's disease. Methods & Procedures: In this experimental group study, 18 patients with Huntington's disease completed a test that assessed basic language abilities as well as tests from a battery of tasks that explored the ability to comprehend more complex information. The test battery assessed the ability to comprehend logico-grammatical sentences, ambiguous information and inferred meaning on sentence and discourse levels. Outcomes & Results: In comparison with results from pair-matched participants in a control group, matched for gender, age and education, the group of individuals with Huntington's disease had significantly more problems with all tasks requiring more complex cognitive processing. There was a correlation, as well as tendencies towards correlations, between results in the group of individuals with Huntington's disease and stage of the disease. However, results within the stage groups were heterogeneous, and some individuals in an early stage of the disease sometimes performed as well as others in a late stage. Conclusions & Implications: It is likely that, in complex discourse tasks, individual differences in cognitive capacity may contribute and override other differences related to stage of disease. These results indicate that it is important to assess comprehension even in early stages of Huntington's disease, with tests that are sensitive to subtle language disorders, to reduce communication problems for the individuals concerned and their conversational partners. [ABSTRACT FROM AUTHOR]

This study examined the first participants who registered for the Huntington's disease predictive testing program 1990–1995 in Stockholm, Sweden. A psychosocial investigation was performed to evaluate potential effects of the presymptomatic testing. The results showed no significant differences between 13 genecarriers and 21 noncarriers in pretest attitudes, expectations, general well‐being, life satisfaction and lifestyle, the need for support, estimated sense of well‐being or degree of health. However, both groups showed high suicidal ideation and self‐injurious behavior. Noncarriers had a very high frequency of attempted suicide, and both groups had similarly pronounced psychiatric dysfunction. Their relatives also had high frequencies of psychiatric diseases, suicide or suicidal attempts. Most of the participants had a desire to meet a psychologist or a social worker. The need for counseling, using a well designed protocol, and the importance of focusing on suicide risk of participants in predictive testing programs is emphasized. [ABSTRACT FROM AUTHOR]

Background: There is a lack of studies of Huntington's disease (HD) in immigrants., Objective: To study the association between country of birth and incident HD in first-generation immigrants versus Swedish-born individuals and in second-generation immigrants versus Swedish-born individuals with Swedish-born parents., Methods: Study populations included all adults aged 18 years and older in Sweden, i.e., in the first-generation study 6,042,891 individuals with 1034 HD cases and in the second-generation study 4,860,469 individuals with 1001 cases. HD was defined as having at least one registered diagnosis of HD in the National Patient Register. The incidence of HD in different first-generation immigrant groups versus Swedish-born individuals was assessed by Cox regression, expressed as hazard ratios (HRs) and 95% confidence intervals (CI). The models were stratified by sex and adjusted for age, geographical residence in Sweden, educational level, marital status, and neighborhood socioeconomic status., Results: Mean age-standardized incidence rates per 100,000 person-years were for all Swedish-born 0.82 and for all foreign born 0.53 and for all men 0.73 and for all women 0.81, with the highest incidence rates for the group 80-84 years of age. After adjusting for potential confounders, the HRs were lower in women in the first- and second-generation, i.e., 0.49 (95% CI 0.36-0.67) and 0.63 (95% 0.45-0.87), respectively, and also among women from Finland or with parents from Finland., Significance: In general, the risk of HD was lower in first-generation and second-generation immigrant women but not among male immigrants., (© 2021. The Author(s).)