Silent destruction: hidden muscle wasting and body decline in early Huntington's disease

Huntington´s Disease (HD) is an autosomal dominant, neurodegenerative disorder with characteristic motor, behavioural, and cognitive impairment. Mutant Huntingtin may also affect peripheral tissue. We aimed to assess skeletal muscle (SMM) and fat mass, sarcopenia (EWGSOP2), and malnutrition in HD patients in early disease stages compared to age- and sex-matched healthy subjects. Body composition was evaluated by bioelectrical impedance analysis. The Unified HD Rating Scale and cognitive assessments were used for clinical characterization. Twenty early-stage HD patients (45% females) with a median age of 57 years, body mass index of 22 kg/m², Total Motor Score of 17 points, and Total Functional Capacity of 10 points were included consecutively and prospectively. Confirmed sarcopenia (15%, n = 3) was uncommon. Appendicular SMM index was reduced in 60% (n = 12) and body fat mass in 35% (n = 7). SMM reduction was significantly associated with low weight (p = 0.049) and body fat (p = 0.048). Patients in disease-stage2 (n = 11) had a lower weight (p = 0.009) and body fat (p = 0.008) than patients in disease-stage1 (n = 9; i.e., patients without functional decline). Weight was also lower (p = 0.011) when compared to 20 healthy controls (45% females; median age 56 years). Fifty-five % of HD patients were at risk for malnutrition or malnourished (Mini Nutritional Assessment). The latter correlated with weight (r_s = 0.724, p < 0.001), SMM (r_s = 0.473, p = 0.035), body fat mass (r_s = 0.611, p = 0.004), motor symptoms (r_s = - 0.519, p = 0.019), independence (r_s = 0.450, p = 0.046), and executive function (r_s = 0.526, p = 0.017). Reduction of muscle or fat mass and malnutrition are common even in early-stage HD, which may contribute to progressive wasting and dependence.