BACKGROUND: Huntington's disease (HD) is a genetic, neurodegenerative disease. Due to the progressive nature of HD and the absence of a cure, (health-related) quality of life ((HR)QoL) is an important topic. Several studies have investigated (HR)QoL in HD, yet a clear synthesis of the existing literature is lacking to date. We performed a systematic review on self-reported (HR)QoL, and factors and intervention effects associated with (HR)QoL in premanifest and manifest HD gene expansion carriers (pHDGECs and mHDGECs, respectively). METHODS: PubMed, EMBASE, Web of Science, and PsycINFO were searched systematically from September 17th, 2021, up to August 11th, 2022. Methodological and conceptual quality of the included studies was assessed with two appraisal tools. RESULTS: 30 out of 70 eligible articles were included. mHDGECs experienced lower (HR)QoL compared to pHDGECs and controls, whereas mixed findings were reported when compared to other neurological diseases. Several factors were associated with (HR)QoL that might contribute to lower (HR)QoL in mHDGECs, including depressive symptoms, physical and psychological symptoms, lower functional capacity, lower support, and unmet needs. Multidisciplinary rehabilitation programs and a respiratory muscle training were beneficial for (HR)QoL in mHDGECs. DISCUSSION: (HR)QoL is experienced differently across the course of the disease. Although (HR)QoL is key for understanding the impact of HD and the effect of symptomatic treatment, there is a need to improve the methodological and conceptual shortcomings that were found in most studies, especially regarding the conceptual clarity when reporting on QoL and HRQoL. Suggestions for strengthening these shortcomings are provided in this review.

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine Charles University and General University Hospital Prague 12821 Prague Czech Republic

Department of Neurology Leiden University Medical Center 2300 RC Leiden The Netherlands

Department of Neurology University Hospital Ulm 89081 Ulm Germany

Department of Neuropsychiatry kbo Isar Amper Klinikum 84416 Taufkirchen Germany

Department of Psychiatry Leiden University Medical Center 2300 RC Leiden The Netherlands

Department of Public Health and Primary Care Leiden University Medical Center PO Box 9600 2300 RC Leiden The Netherlands

Huntington Center Topaz Overduin 2225 SX Katwijk aan Zee The Netherlands

National eHealth Living Lab Leiden University Medical Center Leiden The Netherlands

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