## 4 Discussion
In the second semester of 2020, PD-related symptoms and the independence in activity of daily living significantly worsened in the whole sample. Most patients showed a stable functional condition in the year immediately preceding the pandemic (as measured by the UPDRS II %score change in 2018-2019). Between 2019 and 2020, we found a trend towards worsening in UPDRS-II and UPDRS-III, which was not explained by age, disease duration, or severity. Most importantly, patients with lower functional impairment experienced a greater worsening in their functional condition. The trend towards worsening was confirmed in 2020-2021 for UPDRS-II even at a lower extent, though not for UPDRS-III, whose scores remained relatively stable. Also, non-motor symptoms showed a trend toward worsening in 2019-2020 that was maintained in the subsequent year. Other surveys reported similar findings in different cohorts of patients with PD. In particular, [PERSON] et al. described a worsening of motor and non-motor symptoms in 68.9% of sample subjects [34]. [PERSON] et al. reported a subjective worsening of parkinsonian symptoms in 65.7% of interviewed patients in Spain [33], whereas [PERSON] et al. described such a negative outcome in 30% of their subjects, in Italy [35]. The results of the regression analysis lead us to hypothesize that the impact of the lockdown mostly affected subjects with milder disability at the time COVID-19 hit our country, i.e., those who most suffered from the mobility restrictions imposed by the lockdown. According to these findings, patients with PD exhibit psychological vulnerability and poor resilience to social isolation, irrespective of age and disease severity. Emotional and behavioral adaptation to stressful situations may be impaired in patients with PD due to different factors, like a high prevalence of depressive disorders [36], impaired modulation of autonomic nervous system [37], impaired interpretation of other emotions [38], and impaired selection of proper coping strategies [39]. Moreover, our survey demonstrated that the number of neurologic visits per subject per year was shortened by around 50% in 2020. In addition, the percentage of patients undergoing at least one rehabilitation cycle in a year dropped from 87% (on average in 2018-2019) to 29% in 2020. It is reasonable to argue that people used to performing regular motor training, as recommended in our care pathway, were most disadvantaged by being cut off from rehabilitation provision. Our hypothesis is in line with the findings by other authors who pointed out the effects of physical activity changes in patients with PD during COVID-19 lockdown [15; 32; 40; 41]. The reduced access to health care services could be related not only to a reduced supply but also to a reduced demand due to individuals' fear of contracting the virus when accessing the hospital [42] or to the difficulty in getting to the hospital because of the shortage of transport [43]. It has been reported that the longer the history of PD, the greater the difficulty and the fear of accessing hospitals or health facilities [44]. In addition, as the disease progresses, the grade of disability increases, just like the care needs. These data could explain the significant correlation between worsening functional status after the first year of the COVID-19 pandemic and disease duration and UPDRS II score, in line with [PERSON] et al. [45]. In our sample, the execution of at least one cycle of rehabilitation, including telerehabilitation, in 2020 was associated with a lower (though not significant) risk of worsening functional status. This finding leads to emphasizing the importance of physical activity and supports the need for finding alternative tools to ensure a regular engagement of patients with PD in rehabilitation sessions, even remotely delivered. Physical activity, especially aerobic exercise, provides significant advantages for health [46], contributing to slowing down disease progression and, in some cases, improving clinical outcomes [47].