Body Mass Index Is Significantly Associated With Disease Severity in Spinocerebellar Ataxia Type 2 Patients

Abstract

A BS TRACT: Background: Spinocerebellar ataxia type 2 is a progressive neurodegenerative disorder due to an unstable expansion of a CAG repeat in the ATXN2 gene. Although weight loss has been associated with disease progression in several neurodegenerative conditions, it has been barely assessed in patients with spinocerebellar ataxia type 2. Objective: The objective of this study was to test whether body mass index is altered in patients with spinocerebellar ataxia type 2 with varying expansion sizes from early to late disease stages. Methods: A cross-sectional case-control study was performed, which included 222 clinically and molecularly diagnosed patients and 214 sex-and age-matched healthy individuals. ATXN2 genotypes and sex were considered as risk factors. Clinical outcomes included the body mass index, age at onset, disease duration, Scale for the Assessment and Rating of Ataxia score, disease stage, dysphagia, and progression rate. Multiple linear regression models were generated.Results: Body mass index was significantly decreased in male patients, but not in female patients, relative to control subjects. In addition to sex, body mass index was significantly associated with age at onset and progression rate. Conversely, body mass index, along with repeat length in ATXN2 expanded alleles and disease duration, was associated with Scale for the Assessment and Rating of Ataxia score. In addition, body mass index, along with the age at onset and the repeat length in ATXN2 normal and expanded alleles, has a significant influence on progression rate. Conclusions: Body mass index might be a useful biomarker of disease severity, particularly in male patients with spinocerebellar ataxia type 2 in the context of nutritional interventions or clinical trials assessing the efficacy of promising new drugs.

Hypothalamic Atrophy, Expanded CAG Repeat, and Low Body Mass Index in Spinocerebellar Ataxia Type 3

“…This study confirmed the negative association between CAG repeat length and BMI in SCA3 patients. This association has also been observed in other CAG repeat expansion disorders such as SCA2 and HD, 5,32,33 suggesting BMI as a disease biomarker shared by several polyglutamine diseases 32 . Extending a pioneering study showing a correlation between CAG repeat number and BMI in SCA3, 5 we provide further evidence that this association is partly mediated by tubular hypothalamic atrophy.…”

“…This association has also been observed in other CAG repeat expansion disorders such as SCA2 and HD, 5,32,33 suggesting BMI as a disease biomarker shared by several polyglutamine diseases. 32 Extending a pioneering study showing a correlation between CAG repeat number and BMI in SCA3, 5 we provide further evidence that this association is partly mediated by tubular hypothalamic atrophy. This mediation effect suggests that hypothalamic atrophy may be related to mutant ataxin-3 toxicity per se, the predominant pathology caused by CAG expansion.…”

Identification of the Prodromal Symptoms and Pre-Ataxic Stage in Cerebellar Disorders: The Next Challenge

“…A combination of clinical scales with quality-of-life measures, wearable sensors allowing free-living motor activity monitoring, neuroimaging biomarkers (MRI, MR spectroscopy, DTI) and fluid biomarkers (blood, CSF) is likely the best approach, not only to identify conversions from the asymptomatic stage to symptomatic condition, but also for the general monitoring of ataxias [37,38]. Pure clinical tools, such as the evaluation of the body mass index should not be excluded, as shown recently for BMI, which is significantly decreased in SCA2, with an association with age at onset and progression rate [39]. We may also have to re-consider how trials are designed in patients' registries of CAs given the major heterogeneity in clinical profiles and progression.…”

Circulating CircRNAs Panel Acts as a Biomarker for the Early Diagnosis and Severity of Parkinson’s Disease

“…Parkinson disease (PD) is a chronic neurodegenerative disease. The incidence of PD is closely related to population aging ( Almaguer-Mederos et al, 2021 ). With the aggravation of population aging in China, the incidence of PD is also increasing.…”