Factors Influencing Health-Related Quality of Life of Patients with Spinocerebellar Ataxia
Authors: Weber Niklas , Buchholz Maresa , Rädke Anika , Faber Jennifer , Schmitz-Hübsch Tanja , Jacobi Heike , Klockgether Thomas , Hoffmann Wolfgang , Michalowsky Bernhard ,   the EUROSCA study group, du Montcel Sophie Tezenas , Bauer Peter , Giunti Paola , Cook Arron , Labrum Robyn , Parkinson Michael H. , Durr Alexandra , Brice Alexis , Charles Perrine , Marelli Cecilia , Mariotti Caterina , Nanetti Lorenzo , Panzeri Marta , Rakowicz Maria , Sulek Anna , Sobanska Anna , Schöls Ludger , Hengel Holger , Baliko Laszlo , Melegh Bela , Filla Alessandro , Antenora Antonella , Infante Jon , Berciano José , van de Warrenburg Bart P. , Timmann Dagmar , Szymanski Sandra , Boesch Sylvia , Kang Jun-Suk , Pandolfo Massimo , Schulz Jörg B. , Molho Sonia , Diallo Alhassane ,   the ESMI study group, Hübener-Schmid Jeanette , Santana Magda , Grobe-Einsler Marcus , Koyak Berkan , Raposo Mafalda , Lima Manuela , Garcia-Moreno Hector , Giunti Paola , Pereira de Almeida Luís , van de Warrenburg Bart , van Gaalen Judith , Timmann Dagmar , Thieme Andreas , Reetz Kathrin , Dogan Imis , Wilke Carlo , Schöls Ludger , Riess Olaf , Synofzik Matthis , de Vries Jeroen , Infante Jon , Gulin Oz , Joers James , Onyike Chiadikaobi , Povazan Michal , Ratai Eva-Maria , Schmahmann Jeremy 
Published: January 2024

Abstract
Background
Little is known about the progression of health-related quality of life (HRQoL) and predicting factors in spinocerebellar ataxia (SCA). Such knowledge is crucial to identify modifiable factors promoting everyday life with SCA and attenuating HRQoL decline.

Objectives
This study is to assess HRQoL progression and identify factors affecting SCA patients’ HRQoL.

Methods
Longitudinal data (three-year follow-up) of 310 SCA patients of the European SCA3/Machado-Joseph-Disease Initiative (ESMI) (2016-2022) and 525 SCA patients (SCA1, SCA2, SCA3 or SCA6) of the EUROSCA natural history study cohort (2006–2015) were assessed. Both large cohort studies share standardized assessments of clinical measures, SARA, INAS, PHQ-9, and HRQoL (EQ-5D-3L). The association between HRQoL and clinical measures was assessed by Spearman Correlation (rs). Multivariable panel regression models were performed to evaluate the impact of patients’ socio-demographics, age of onset, SCA type and body mass index (BMI), and clinical measures on HRQoL progression.

Results
HRQoL significantly decreased over one (− 0.014, p = 0.095), two (− 0.028, p = 0.003), and three years (− 0.032, p = 0.002). Ataxia severity and mental health strongly correlated with HRQoL (rsSARA = − 0.589; rsPHQ-9 = − 0.507). HRQoL more intensively declined in male (ß = − 0.024, p = 0.038) patients with an earlier age of onset (ß = 0.002, p = 0.058). Higher progression of ataxia severity (ß = − 0.010, p ≤ 0.001), mental health problems (ß = − 0.012, p < 0.001), and higher BMI (ß = − 0.003, p = 0.029) caused more severe decline of patients’ HRQoL over time.

Discussion
In absence of curative treatments, stronger focus on mental health and weight influence could help clinical evaluation and accompany treatment improving SCA patients’ HRQoL, especially in male patients with early disease onset.