Huntington’s disease (HD) is an autosomal dominant progressive brain disorder, caused by a pathological expansion of a CAG repeat that encodes the huntingtin gene. This genetic neurodegenerative rare disease is characterized by cognitive, motor, and neuropsychiatric manifestations. The aim of the treatment is symptomatic and addresses the hyperkinetic disorders (chorea, dystonia, myoclonus, tics, etc.) and the behavioural and cognitive disturbances (depression, anxiety, psychosis, etc.) associated with the disease. HD is still a complex condition in need of innovative and efficient treatment. The long-term goal of pharmacogenetic studies is to use genotype data to predict the effective treatment response to a specific drug and, in turn, prevent potential undesirable effects of its administration. Chorea, depression, and psychotic symptoms have a substantial impact on HD patients’ quality of life and could be better controlled with the help of pharmacogenetic knowledge. We aimed to carry out a review of the available publications and evidence related to the pharmacogenetics of HD, with the objective of compiling all information that may be useful in optimizing drug administration. The impact of pharmacogenetic information on the response to antidepressants and antipsychotics is well documented in psychiatric patients, but this approach has not been investigated in HD patients. Future research should address several issues to ensure that pharmacogenetic clinical use is appropriately supported, feasible, and applicable.

Background/Objectives: Huntington’s disease (HD) is a neurodegenerative movement disorder associated with significant disability and impairment of Activities of Daily Living (ADLs). The impact of upper limb disability on quality of life (QoL) and its influence on ADLs is not well known yet. The aim of this study was to describe the manipulative dexterity, strength, and manual eye coordination of patients with manifest and premanifest-HD compared to healthy individuals and to analyze its influence on ADLs and QoL. Methods: We performed an observational, cross-sectional study including 71 ambulatory participants (27 manifest-HD patients, 15 premanifest-HD, and 29 controls). We gathered sociodemographic data, as well as clinical data, including cognition (MMSE), HD motor severity (Unified HD rating scale, UHDRS-TMS), QoL (Neuro-QoL), and ADLs (HD-ADL). Hand dexterity and strength in the dominant and non-dominant hand were assessed with the Nine Hole Peg Test, Ten Neurotest, Nut and Bolt Test, dynamometry, and Late-Life FDI. Analysis of covariance (ANCOVA) models were performed to investigate differences in hand function between manifest-HD, premanifest-HD, and controls. Results: Manifest-HD patients had significantly worse performance in manual and finger dexterity, fine-motor coordination, and poorer handgrip strength than premanifest-HD and controls. Premanifest-HD required more time to complete the test than controls. Significant correlations were found between hand variables and Late-Life FDI, Neuro-QoL, HD-ADL, and UHDRS-TMS. Conclusions: HD affects manipulative dexterity and hand function in premanifest and manifest patients. Therefore, to prevent disability and decreased QoL, evaluating the progression of upper limb dysfunction in HD is important to offer the best possible therapeutic interventions.

Accelerometers can estimate the intensity, frequency, and duration of physical activity in healthy adults. Although thresholds to distinguish varying levels of activity intensity using the Actigraph wGT3X-B have been established for the general population, their accuracy for Huntington’s disease (HD) is unknown. We aimed to define and cross-validate accelerometer cut-points for different walking speeds in adults with mild to moderate HD. A cross-sectional, multicentre, case-control, observational study was conducted with a convenience sample of 13 symptomatic ambulatory HD participants. The accelerometer was placed around the right hip, and a heart monitor was fitted around the chest to monitor heart rate variability. Participants walked on a treadmill at three speeds with light, moderate and vigorous intensities. Correlation and receiver operation curve analyses were performed between the accelerometer magnitude vector with relative oxygen and heart rate. Optimal cut-points for walking speeds of 3.2 km/h were ≤2852; 5.2 km/h: >2852 to ≤4117, and in increments until their maximum velocity: >4117. Our results support the application of the disease-specific cut-points for quantifying physical activity in patients with mild to moderate HD and promoting healthy lifestyle interventions.

Introduction. Huntington ' s disease (HD) is a rare neurodegenerative disorder. Reliable information about nutritional status, especially body composition from individuals with HD is critical for clinical care and research. The ease of application and portability of multiple frequencies bioelectrical impedance analysis (mfBIA) make it an attractive tool for measuring body composition, but its accuracy in HD is unknown. Aim. To evaluate the accuracy of mfBIA vs. Dual X-ray absorptiometry (DEXA) in HD. Patients and methods. Cross-sectional, observational, and single-center study. HD severity was measured using motor subscale of the unified Huntington's disease rating scale (m-UHDRS) and the total functional capacity (TFC). Body composition was measured in terms of fat-free mass (FFM), fat mass (FM), fat-free mass index (FFMI), and fat mass index (FMI). Using Bland-Altman plots, we analyzed reliability between DEXA and mfBIA using the Intraclass Correlation Coefficient with 95% confidence intervals (CI) and bias estimates for all. Results. We included 16 patients with HD, 7 men, and 9 women, median age of 58.5 (32;68) years, TFC: 10 (3;13), and m-UHDRS: 31 (7;85). The reliability between mfBIA and DEXA were high for FFMI in men: 0.88 (95% CI 0.17-0.98), and women: 0.90 (95% CI 0.61- 0.98); for FMI, men: 0.97 (95% CI 0.83-0.99), and women: 0.91 (95% CI 0.68-0.98). Compared to DEXA, mfBIA slightly overestimated FFM, FM, FMI and FFMI in men and underestimated FFMI in women. Conclusions. mfBIA is an easy-to-use, safe, non-invasive, accurate method for measuring body composition and nutritional status in patients with mild-moderate HD.

BACKGROUND Huntington's disease (HD) is an inherited neurodegenerative disorder, autosomal dominant caused by an expanded triplet (CAG) repeat in HTT gene on chromosome 4p, with a prevalence of 14/100,000 people. Major clinical features are involuntary movements, psychiatric symptoms, and cognitive dysfunction [1, 2]. There is no curative treatment for HD, with only symptomatic pharmacological treatments available. Due to the progressive course of neurodegeneration, HD patients progressively lose their functional capacity with increased dependence and risk for cardiovascular events, sepsis, and death.[3] Among the different clinical manifestations, weight loss and energy deficit (ED) have been described in HD, even in the early stages of the disease, contributing to the progression. The underlying mechanisms contributing to weight loss and the energy requirement in different stages of HD remain unknown.[4, 5] Surprisingly, HD patients often report an increased appetite with higher energy intake,[4, 6] and higher weight is associated with a slower rate of disease progression. [7] In this regard, the alterations in the brain and muscle metabolism and weight loss underscore that ED is likely an early phenomenon in the cascade of events leading to HD pathogenesis.[7] Biochemical studies support that mitochondrial dysfunction is a relevant factor in the alteration of ED in HD, and the hypothalamic dysfunction would contribute to weight loss.[5] Calories are units that measure the energy in food and the energy produced, stored, and utilized by living organisms. One calorie is defined as the amount of heat energy required to raise 1 g of water by 1°C [8]. TEE is the amount of energy an individual uses to maintain essential body functions (respiration, circulation, digestion) as a result of physical activity (PA).[9] TEE is then the sum of several components: resting energy expenditure (REE; 60–80%), PA (20–40%), and diet-induced thermogenesis (7–10%).[10] Adequate EB is achieved when TEE equals energy intake, defined as the energy consumed via food and beverage [8]. Previous literature in HD suggests that EB is not adequate, either due to reduced food intake (HD patients frequently suffer from dysphagia), abnormal REE secondary to structural damage (hypothalamic, mitochondrial disturbances produced by the neurodegeneration process per se), or abnormal PA due to chorea, or decreased mobility.[5, 11] Few studies on EB in neurodegenerative diseases, including HD, have comprehensively addressed and analyzed its contributing components.[12] Because most of these EB studies have been performed in controlled-laboratory research, there is a lack of knowledge about EB estimates in free-living environments. Valid measurement of PA in free-living environments is needed to describe and quantify PA and to assess the effectiveness of interventions and health promotion techniques.[13] Since their introduction as an objective measure of free-living PA in the early 1980s,[14] accelerometers have become a staple of the PA assessment repertoire. They have been used extensively in validating self-reported PA surveys, as outcome measures in intervention studies, and in research designed to identify the psychosocial and environmental correlates of PA behaviors. Accelerometry has the potential to provide information about the intensity, duration, and frequency of PA. A challenge in accelerometry-based approaches is that the raw outputs (typically called counts) must be converted into meaningful and interpretable units.[13] In most calibration accelerometer studies, counts are converted to oxygen consumption, metabolic equivalents (METs), or caloric expenditure as meaningful and interpretable measurements of PA intensity. [15] However, to predict energy expenditure related to PA, we should differentiate community-based samples vs. disease-based samples and calibrate these accelerometers with accurate cut points to distinguish levels of PA (mild, moderate, or vigorous). Sarcopenia defined as decreased muscle mass, is another important aspect of weight loss in HD and leads to higher dependency rates.[16] Overall, muscle mass can be quantified at different levels of body composition. Some methods, such as dual-energy X-ray absorptiometry (DXA), or Magnetic Resonance Imaging, have high validity but are complex and expensive.[17] In this regard, BIA is inexpensive and easy to perform in most settings, being the preferred method for clinical practice.[17] However, as in any other measurement, the accuracy of BIA in HD has not been established. Considering the lack of knowledge about EB in HD and its impact on body composition, it is important to conduct a study to validate different tools to calculate the EB and body composition in HD, and to provide preliminary data on EB in HD, which is the main objective. The present publication presents the protocol for this study. OBJECTIVE SPECIFIC GOALS The main aim of this study is to calculate the EB in patients with HD. Specific objectives of this study are 1) to validate the use of accelerometers to quantify energy expenditure related to PA under controlled conditions for HD patients using Indirect Calorimetry (IC) as the gold standard; 2) to study the EB (i.e., EE and energy caloric intake) in HD patients and to compare it with healthy controls; 3) to validate the use of BIA for HD to study body composition using DXA as the gold standard; 4) to study the impact of EB on functional capacity, sarcopenia status, the severity of motor and non-motor symptoms, psychiatric, and cognitive manifestations, QoL, and caregiver burden in HD patients. METHODS MATERIALS AND METHODS DESIGN This study is a protocol of a cross-sectional observational, multicentre study of a cohort of patients with HD patients compared to age, gender matched-control subject. The protocol of this study followed the STROBE statement reporting criteria for protocol case-control reports...