Affiliations: UCL Institute of Neurology, University College London, Queen Square, London, UK | London School of Hygiene and Tropical Medicine, London, UK | Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada | Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands | Department of Genetics and Cytogenetics, and INSERM UMR S679, APHP Hôpital de la Salpêtrière, Paris, France | School of Psychology, Psychiatry, and Psychological Medicine, Monash University, Clayton Campus, VIC, Australia | University of Manchester, Manchester Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
Note:  Correspondence to: Joy Read, UCL Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK. Tel.: +44 20 344 84056; Fax: +44 207 611 0129; E-mail: firstname.lastname@example.org
Abstract: Background: Given the multifaceted nature of this inherited neurodegenerative condition, typically affecting adults in mid-life, it is perhaps not surprising that studies indicate poorer Health Related Quality of Life (HrQoL) in those with the gene-expansion and, by association, in their families. Objective: This study aimed to extend the current literature by exploring specific life domains, including at an earlier disease stage than usually reported in the HRQoL literature, and in a subgroup of gene-negative partners. Methods: 355 participants from the TRACK-HD cohort (120 Controls, 118 Pre-HD and 117 early-HD) completed standardised self-report measures of HrQoL (SF36 and QoLI), underwent clinical assessments of capacity and motor function (UHDRS), semi structured interviews assessing neuropsychiatric symptoms (PBA-s), completed paper and computerized cognitive tasks and assessment of behaviours associated with damage to frontal brain circuits (FrSBe). Results: Each gene-expanded group scored statistically significantly lower than gene-negative sibling controls on the SF36 General Health subscale; neuropsychiatric symptoms and executive dysfunction were associated with reduced HrQoL. Those with Stage II disease reported statistically significantly lower HrQoL than gene-negative controls across physical, emotional and social life domains. Those partnered with manifest participants reported lower HrQoL in the social domain compared to those partnered with at-risk participants furthest from disease onset; and perseverative symptoms in manifest partners were found to be related to lower HrQoL in their gene-negative partners. HrQoL in gene-negative partners of pre-manifest individuals was associated with pre-manifest individuals' neuropsychiatric and cognitive function. Conclusions: Understanding the nature and timing of disruption to the HrQoL in people who are pre-manifest and diagnosed with HD, and their gene-negative partners, can inform the development of appropriate strategies and interventions.
Keywords: Huntington's disease, quality of life, TRACK-HD, life domains, cognitive function, neuropsychiatric function