## 3 Results
### Primary Endpoints  
Table 1 presents the results of the descriptive and comparative statistics of primary endpoint measures across the period of interest. Overall, the mean values of UPDRS-II (15.02 \(\pm\) 8.0) and UPDRS-III (22.63 \(\pm\) 13.1) recorded in 2018 are representative of a varied population of patients with mild to moderate motor impairment and reduced independence in ADL, though generally preserved walking ability. The disabling impact of non-motor symptoms (NMSS score = 65.89 \(\pm\) 34.6 in 2018) is mild to moderate as well. The analysis of changes of primary outcome measures in the 2018-2019 time period showed high inter-individual variability in the trends of UPDRS-II, UPDRS-III, and NMSS scores with mean values of 0.3% (\(\pm\)33.0), \(-\)3.8% (\(\pm\)39.3), and \(-\)11.5% (\(\pm\)32.4), respectively. Even if the large  
variability of motor and non-motor symptom progression was confirmed in subsequent years, the matched comparison of % changes observed in 2019-2020, with those recorded in 2018-2019 in the same subjects, showed a statistically significant trend towards increasing for all primary outcome measures. On average, UPDRS-II, UPDRS-III, and NMSS scores increased by 22% (\(\pm\)55.3), 28.8% (\(\pm\)64.2), and 12.5 (\(\pm\)8.1), respectively, at the end of 2020 compared to the year before. In the 2020-2021 period, UPDRS-II, UPDRS-III, and NMSS increased by 12.0% (\(\pm\)58.3), 0.01% (\(\pm\)0.4), and 12.5% (\(\pm\)49.5), respectively. When compared to the changes observed in the previous year, only the UPDRS-III trend was significantly different from the trend observed before. We run a simple regression analysis to look for any correlation between demographic and clinical variables and the progression of primary outcome measures in 2019-2020. Table 2 details the results, showing that only the baseline values of the different measures at the start of 2019 explained the change. Most importantly, it showed that the lower the starting values, the higher the changes in the following year. Age, disease duration, and BMI were not correlated to the trends observed in 2018-2019 and 2020-2021 in the primary outcome measures. When we matched the % changes in UPDRS II, UPDRS III, and NMSS observed in 2018-2019 with their starting values, \begin{table}
\begin{tabular}{p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt}} \hline \hline \multicolumn{1}{c}{} & \multicolumn{3}{c}{**Dependent Variable**} & \multicolumn{1}{c}{**UPDRS II**} & \multicolumn{1}{c}{**UPDRS III**} & \multicolumn{1}{c}{**NMSS**} \\ \multicolumn{1}{c}{**(2019 Values)**} & \multicolumn{1}{c}{**\% Change 2019–2020**} & \multicolumn{1}{c}{**\% Change 2019–2020**} & \multicolumn{1}{c}{**\% Change 2019–2020**} & \multicolumn{1}{c}{**\% Change 2019–2020**} \\ \hline Age & Coeff. 0.569; R2.008 \(p=0.21\) & Coeff. 0.361; R2.002 \(p=0.50\) & Coeff. \(-0.543\); R2.0.010 \(p=0.17\) \\ \hline Disease duration & Coeff. \(-0.347\); R2.002 \(p=0.49\) & Coeff. \(-13.36\); R2.002 \(p=0.02\) & Coeff. \(-0.261\); R2.002 \(p=0.55\) \\ \hline BMI & Coeff. \(-0.558\); R2.002 \(p=0.54\) & Coeff. \(-0.731\); R2.0.003 \(p=0.48\) & Coeff. \(0.139\); R2.0.0001 \(p=0.86\) \\ \hline UPDRS II & Coeff. \(-2.42\); R2.013 \(p=0.0001\) & Coeff.\(-1.24\); R2.0.023 \(p=0.03\) & Coeff. \(-0.109\); R2.0.0001 \(p=0.80\) \\ \hline UPDRS III & Coeff. \(-0.509\); R2.0.013 \(p=0.10\) & Coeff. \(-1.84\); R2.0.128 \(p=0.0001\) & Coeff. \(0.204\); R2.0.003 \(p=0.46\) \\ \hline NMSS & Coeff. \(-0.218\); R2.0.014 \(p=0.09\) & Coeff. \(-0.084\); R2.0.002 \(p=0.58\) & Coeff. \(-0.477\); R2.0.090 \(p=0.0001\) \\ \hline \multicolumn{1}{c}{} & \multicolumn{3}{c}{Legend: BMI = Body Mass Index; Coeff = coefficient; NMSS = Non-Motor Symptoms Scale; UPDRS = Unified Parkinson’s Disease Rating Scale; val: value.} \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Results of the simple regression analysis matching different independent variables with %changes observed in 2019–2020 in the primary outcome measures.