The relationship between the extent of local gray/white matter atrophy, genetic load, and clinical impairment was studied in Huntington's disease (HD) by means of voxel-based morphometry. T1-weighted brain images from 33 patients (mean age 49.5, range 25-73 years) with HD duration of 1 to 15 years were analyzed by correlation of each voxel intensity with the number of CAG triplets and the UHDRS-motor score (P < 0.001). The CAG number correlated inversely with gray matter intensity in the caudate nuclei and with white matter intensity in the both postcentral gyri and the right cerebellum. The UHDRS-motor score correlated inversely with the atrophy of both caudates, right hippocampus, calcarine fissure, and with the white matter along the fourth and lateral ventricles. While atrophy of the caudate nucleus was related to a higher number of CAG triplets and higher UHDRS-motor score, atrophy in other parts of the brain covaried with the two parameters differently: higher genetic load was associated with greater loss of cortical somatosensory projections and the worse UHDRS-motor score was accompanied by increased atrophy of the internal capsule, lower brainstem, hippocampus, and visual cortex. According to our results, the genetic load in HD predicts partially the extent of selective gray/white brain matter atrophy, which is then reflected in the severity of motor impairment.

The relationship between motor symptoms and cognitive impairment in Huntington's disease (HD) is still discussed. We analysed 45 HD patients in various stages using Unified Huntington's Disease Rating Scale motor subscale (voluntary and involuntary components were evaluated separately), verbal memory and executive functions tests. Partial correlations controlling for HD duration and age were used to estimate the relationships among factor scores for motor and cognitive impairment. Voluntary components of motor performance were found to be significantly correlated with verbal short-term memory disturbances (r = -0.361, P = 0.03), with tests of executive functions more dependent on motor performance (r = 0.640, P < 0.01) and also with tests of executive functions less dependent on motor performance (r = 0.461, P < 0.01). Involuntary components did not correlate significantly with any part of cognitive performance.

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.

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