RESUMO
Background: Individuals with Huntington's disease (HD) experience motoric, cognitive, and psychiatric dysfunction. These difficulties can cause maladaptive behaviors that can be very distressing to family and caregivers. Capturing these behaviors in clinical and research settings is crucial. Objectives: To develop and evaluate the psychometric properties of an instrument that is brief, yet comprehensive, in assessing a broad range of behaviors in HD. Methods: A pool of 30 items encompassing common behaviors in HD was generated. Items were scored on a 4-point Likert scale ranging from completely disagree to completely agree, with higher scores indicating greater dysfunction. The self-report measure was piloted on a small sample of individuals with HD. Reliability (test-retest, internal consistency) and validity (convergent, discriminant, criterion) were evaluated. Results: The HD-Behavioral Questionnaire (HD-BQ) demonstrated evidence for reliability with a test-retest correlation coefficient of r = 0.81 and an internal consistency of 0.96. Validity was established with evidence for good convergent, divergent, and criterion validity. A receiver operating characteristic curve showed that the HD-BQ outperformed a similar commonly used measure in diagnostic capability of behaviors in HD. Conclusions: The HD-BQ, a patient self-report measure, was created to more fully explore behavioral issues that people with HD experience in response to limitations of commonly used instruments in the field. Psychometric evidence supports that the HD-BQ is a valid and reliable instrument for the brief, yet comprehensive, assessment of problematic behaviors in HD.
RESUMO
Oxidative stress has long been implicated in the pathophysiology and progression of Huntington's disease (HD). Uric acid (UA) is a naturally occurring antioxidant that is present in the brain and periphery. Growing evidence has implicated UA as a molecular biomarker for several neurodegenerative diseases, most notably Parkinson's disease (PD). In this study, we investigated UA levels in clinical samples from HD patients and normal controls (NCs) and assessed potential relationships between UA levels and disease and clinical data. UA levels were measured in plasma (n = 107) and saliva (n = 178) samples from premanifest (pre-HD) and manifest HD patients and control subjects. Gender effects of UA levels were observed in both biofluids, with male patients showing higher UA levels compared to female patients. Comparisons of UA levels across diagnostic groups, separated by gender, revealed that both plasma and salivary UA levels were significantly lower in female pre-HD and manifest HD patients compared to NCs. Salivary levels of UA were also significantly lower in male manifest HD patients versus controls, but not in plasma. Correlations of peripheral UA levels to clinical data also showed differences according to gender. In male HD patients, both plasma and salivary UA levels were significantly negatively correlated with total functional capacity (TFC), while positive correlations were observed with total motor score (TMS). Female HD patients showed a significant positive correlation between plasma UA levels and TMS, while salivary UA levels from female patients were significantly correlated to disease burden. Finally, in a separate cohort, we show that UA levels are decreased in postmortem prefrontal cortical samples (n = 20) from HD subjects compared to matched controls. These findings suggest that decreased levels of UA in the brains of HD patients can be reflected in peripheral fluids, with salivary measures of UA particularly offering significant promise as a potentially relevant, non-invasive biomarker of disease symptoms and burden. Our findings further highlight the impact of sexual dimorphism in HD pathophysiology.
