Supplementary Material for: Substantia Nigra Hyperechogenicity as a Marker for Parkinson's Disease: A Population-Based Study

<b><i>Background:</i></b> The clinical diagnosis of Parkinson's disease (PD) is currently anchored in its cardinal motor symptoms. According to hospital-based studies, an enlarged echogenicity in the area of the substantia nigra (SN) assessed with transcranial sonography (TCS) may represent a useful biomarker in the diagnosis of PD. <b><i>Objective:</i></b> To evaluate SN hyperechogenicity as a marker for PD in the Bruneck Study cohort, which is representative of the general elderly community. <b><i>Methods:</i></b> The diagnostic accuracy of TCS in distinguishing clinically diagnosed PD from nonparkinsonian subjects was assessed in 574 subjects from this cohort. <b><i>Results:</i></b> There was a good diagnostic accuracy of TCS in distinguishing PD subjects from nonparkinsonian subjects with an area under the curve value of 0.82. At a receiver-operating characteristic curve analysis-based cutoff value for SN hyperechogenicity of 0.18 cm², TCS had a sensitivity of 88.2% (95% confidence interval, CI, 64.4-98.0), a specificity of 77.0% (95% CI 72.8-80.6), a positive predictive value of 12.7% (95% CI 7.8-20.0) and a negative predictive value of 99.4% (95% CI 97.8-100.0) for subjects with clinically definite PD at baseline. When analyzing the same population after 5 years with regard to the presence of known and newly diagnosed PD cases, baseline TCS yielded very similar diagnostic accuracy values. <b><i>Conclusion:</i></b> SN hyperechogenicity may represent a useful biomarker for PD not only in a hospital-based setting but also in the general community

Supplementary Material for: Fatigue-related changes of daily function: most promising measures for the digital age

Background: Fatigue is a prominent symptom in many diseases, and is strongly associated with impaired daily function. The measurement of daily function is currently almost always done with questionnaires, which are subjective and imprecise. With the recent advances of digital wearable technologies, novel approaches to evaluate daily function quantitatively and objectively in real life conditions are increasingly possible. This also creates new possibilities to measure fatigue-related changes of daily function using such technologies. Summary: This review examines in immune-mediated inflammatory and neurodegenerative diseases, which parameters may have the greatest potential to reflect fatigue-related changes of daily function. Key Messages: Results of a standardized analysis of the literature reporting about perception-, capacity- and performance-evaluating assessment tools indicate that changes of the following parameters: physical activity, independence of daily living, social participation, working life, mental status, cognitive and aerobic capacity, and supervised and unsupervised mobility performance have the highest potential to reflect fatigue-related changes of daily function. These parameters thus hold the greatest potential for quantitatively measuring fatigue in representative diseases in real life conditions, e.g. with digital wearable technologies. Furthermore, to the best of our knowledge, this is a new approach to analysing evidence for the design of performance-based digital assessment protocols in human research, which may stimulate further systematic research in this area