The interactions between the age at onset with other pathogenic mechanisms and the interplays between the disease progression and the aging processes in Parkinson’s disease (PD) remain undefined, particularly during the first years of illness. Here, we retrospectively investigated the clinical presentation and evolution of the motor and non-motor symptoms and treatment-related complications during the first 5 years of illness in subjects categorized according to age at onset. A total of 131 subjects were divided into “Early-Onset-PD” (EOPD; onset ≤49 years), “Middle-Onset-PD” (MOPD; onset 50–69 years) and “Late-Onset-PD” (LOPD; onset ≥70 years). The T0 visit was set at the time of the clinical diagnosis; the T1 visit was 5 years (±5 months) later. At T0, there were no significant differences in the motor features among the groups. At T1, the LOPD patients displayed a significantly higher frequency of gait disturbances and a higher frequency of postural instability. Moreover, at T1, the LOPD subjects reported a significantly higher frequency of non-motor symptoms; in particular, cardiovascular, cognitive and neuropsychiatric domains. The presented results showed a significantly different progression of motor and non-motor symptoms in the early course of PD according to the age at onset. These findings contribute to the definition of the role of age at onset on disease progression and may be useful for the pharmacological and non-pharmacological management of PD.

Daily steps could be a valuable indicator of real-world ambulation in Parkinson’s disease (PD). Nonetheless, no study to date has investigated the minimum number of days required to reliably estimate the average daily steps through commercial smartwatches in people with PD. Fifty-six patients were monitored through a commercial smartwatch for 5 consecutive days. The total daily steps for each day was recorded and the average daily steps was calculated as well as the working and weekend days average steps. The intraclass correlation coefficient (ICC) (3,k), standard error of measurement (SEM), Bland–Altman statistics, and minimum detectable change (MDC) were used to evaluate the reliability of the step count for every combination of 2–5 days. The threshold for acceptability was set at an ICC ≥ 0.8 with a lower bound of CI 95% ≥ 0.75 and a SAM < 10%. ANOVA and Mann–Whitney tests were used to compare steps across the days and between the working and weekend days, respectively. Four days were needed to achieve an acceptable reliability (ICC range: 0.84–0.90; SAM range: 7.8–9.4%). In addition, daily steps did not significantly differ across the days and between the working and weekend days. These findings could support the use of step count as a walking activity index and could be relevant to developing monitoring, preventive, and rehabilitation strategies for people with PD.

Background: Recent studies demonstrated the validity, reliability, and accuracy of consumer smartwatches for measuring daily steps in people with Parkinson disease (PD). However, no study to date has estimated the minimal clinically important difference (MCID) for average daily steps (avDS), measured through a consumer smartwatch in people with PD. Objective: This study aimed to calculate the MCID of avDS, measured through a commercial smartwatch (Garmin Vivosmart 4) in people with PD. Methods: People with PD with a disease stage <4, without cognitive impairment, and who were able to walk unaided, wore a Garmin Vivosmart 4 smartwatch for 5 consecutive days on the wrist least affected by the disease, allowing the computation of avDS. To define the 3 levels of MCID for avDS, we used an anchor-based method linked to: (1) scales capturing subtle changes in global mobility and motor functions, (2) clinical and health-related measures, and (3) disease-related patient-reported outcomes. Linear regressions, Student t test, and ANOVA were used to estimate the minimal change in avDS based on anchors relevant change. For each level, the overall MCID was calculated as the average of the variables included, and the range was reported. Results: A total of 100 people with PD were enrolled. Participants took on average 5949 (SD 3034) daily steps, ranging from 357 to 12,620. The MCID of avDS anchored to standardized measures of motor symptoms and mobility was 581 steps/day (range 554‐608) or around 10% of mean avDS in our population. The MCID of avDS anchored to clinical and health-related variables was 1200 steps/day (range 350‐1683), or around 20% of mean avDS in our population. Finally, the MCID of avDS anchored to disease-related patient-reported outcomes was 1592 steps/day (range 594‐2589), or around 27% of the mean avDS in our population. Conclusions: These findings could be relevant for designing future clinical trials involving avDS as a digital mobility outcome in daily life for people with PD and evaluating the effectiveness of the intervention promoting free-living walking in this population.

Background: Average daily steps (avDS) could be a valuable indicator of real-world ambulation in people with Parkinson disease (PD), and previous studies have reported the validity and reliability of this measure. Nonetheless, no study has considered disease phenotype, stage, and severity when assessing the reliability of consumer wrist-worn devices to estimate daily step count in unsupervised, free-living conditions in PD. Objective: This study aims to assess and compare the reliability of a consumer wrist-worn smartwatch (Garmin Vivosmart 4) in counting avDS in people with PD in unsupervised, free-living conditions among disease phenotypes, stages, and severity groups. Methods: A total of 104 people with PD were monitored through Garmin Vivosmart 4 for 5 consecutive days. Total daily steps were recorded and avDS were calculated. Participants were dichotomized into tremor dominant (TD; n=39) or postural instability and gait disorder (PIGD; n=65), presence (n=57) or absence (n=47) of tremor, and mild (n=65) or moderate (n=39) disease severity. Based on the modified Hoehn and Yahr scale (mHY), participants were further dichotomized into earlier (mHY 1‐2; n=68) or intermediate (mHY 2.5‐3; n=36) disease stages. Intraclass correlation coefficient (ICC; 3,k), standard error of measurement (SEM), and minimal detectable change (MDC) were used to evaluate the reliability of avDS for each subgroup. The threshold for acceptability was set at an ICC ≥0.8 with a lower bound of 95% CI ≥0.75. The 2-tailed Student t tests for independent groups and analysis of 83.4% CI overlap were used to compare ICC between each group pair. Results: Reliability of avDS measured through Garmin Vivosmart 4 for 5 consecutive days in unsupervised, free-living conditions was acceptable in the overall population with an ICC of 0.89 (95% CI 0.85‐0.92), SEM below 10%, and an MDC of 1580 steps per day (27% of criterion). In all investigated subgroups, the reliability of avDS was also acceptable (ICC range 0.84‐0.94). However, ICCs were significantly lower in participants with tremor (P=.03), with mild severity (P=.04), and earlier stage (P=.003). Moreover, SEM was below 10% in participants with PIGD phenotype, without tremor, moderate disease severity, and intermediate disease stage, with an MDC ranging from 1148 to 1687 steps per day (18%‐25% of criterion). Conversely, in participants with TD phenotype, tremor, mild disease severity, and earlier disease stage, SEM was >10% of the criterion and MDC values ranged from 1401 to 2263 steps per day (30%‐33% of the criterion). Conclusions: In mild-to-moderate PD, avDS measured through a consumer smartwatch in unsupervised, free-living conditions for 5 consecutive days are reliable irrespective of disease phenotype, stage, and severity. However, in individuals with TD phenotype, tremor, mild disease severity, and earlier disease stages, reliability could be lower. These findings could facilitate a broader and informed implementation of avDS as an index of ambulatory activity in PD.

Background: Fatigue is a common and debilitating non-motor symptom (NMS) in Parkinson’s disease (PD), significantly affecting patients’ quality of life. MAO-B inhibitors are effective therapy for motor symptoms and fluctuations and may also play a role in fatigue management. Methods: We searched PubMed for English-language articles (January 1978–August 2024) using keywords including “selegiline”, “rasagiline”, “safinamide”, “MAO-B”, “fatigue”, and “Parkinson’s disease”. Clinical trials, observational, and preclinical studies were included. Results: While the role of MAO-B inhibitors in fatigue remains unclear, evidence suggests potential benefits. Selegiline has shown effectiveness in improving fatigue in animal models, supporting its potential utility in treating fatigue and motivational impairments in PD patients. Rasagiline has been associated with reduced fatigue progression in early PD, with some studies showing significant improvements compared to placebo. Safinamide, with its dual action as an MAO-B inhibitor and glutamate modulator, may further enhance fatigue management. Its ability to reduce glutamate release is particularly relevant, given the role of glutamate overactivity in PD-related fatigue. Studies indicate safinamide can significantly reduce fatigue levels. Conclusions: Fatigue in PD is a complex symptom with multiple contributing factors. While MAO-B inhibitors may support fatigue management, their precise role and optimal use require further investigation.