The Story behind the Mask: A Narrative Review on Hypomimia in Parkinson's Disease.

Facial movements are crucial for social and emotional interaction and well-being. Reduced facial expressions (i.e., hypomimia) is a common feature in patients with Parkinson's disease (PD) and previous studies linked this manifestation to both motor symptoms of the disease and altered emotion recognition and processing. Nevertheless, research on facial motor impairment in PD has been rather scarce and only a limited number of clinical evaluation tools are available, often suffering from poor validation processes and high inter- and intra-rater variability. In recent years, the availability of technology-enhanced quantification methods of facial movements, such as automated video analysis and machine learning application, led to increasing interest in studying hypomimia in PD. In this narrative review, we summarize the current knowledge on pathophysiological hypotheses at the basis of hypomimia in PD, with particular focus on the association between reduced facial expressions and emotional processing and analyze the current evaluation tools and management strategies for this symptom, as well as future research perspectives.

Cerebral hemodynamics and cognitive functions in the acute and subacute stage of mild ischemic stroke: a longitudinal pilot study.

The association between cerebral hemodynamics and cognitive impairment has been reported in neurodegenerative and cerebrovascular disorders (CVD). However, it is still unclear whether changes occur in the acute phase of CVD. Here we investigated cognitive and hemodynamic parameters and their association in patients with CVD during the acute and subacute phases. Seventy-three patients with mild stroke, not undergoing endovascular treatment, were recruited. All subjects were devoid of intracranial or external carotid stenosis, significant chronic cerebrovascular pathology, dementia or non-compensated cardiovascular diseases. Patients were evaluated within 7 days from symptoms onset (T1) and after 3 months (T2). Clinical and demographic data were collected. NIHSS, MoCA, FAB, and Word-Color Stroop test (WCST) were used to evaluate disease severity and cognitive functions. Basal hemodynamic parameters in the middle cerebral artery were measured with transcranial Doppler. Differences between T2 and T1, correlations between cognitive and hemodynamic variables at T1 and T2, as well as correlations between the T2-T1 variation in cognitive and hemodynamic parameters were assessed. At T1, cognitive performance of MoCA, FAB, and WCST was lower compared with T2; and pulsatility index, a parameter reflecting distal vascular resistance, was higher. However, no correlations between the changes in cognitive and hemodynamic variables were found; therefore, the two seems to be independent phenomena. In the acute phase, the linear association between cerebral blood flow and cognitive performances was lost, probably due to a differential effect of microenvironment changes and vascular-specific phenomena on cognition and cerebral hemodynamics. This relationship was partially restored in the subacute phase.

Four Days Are Enough to Provide a Reliable Daily Step Count in Mild to Moderate Parkinson's Disease through a Commercial Smartwatch.

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.

Levodopa Carbidopa Intestinal Gel in Advanced Parkinson's Disease: DUOGLOBE Final 3-Year Results.

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) improves motor and non-motor symptoms in patients with advanced Parkinson's disease (aPD). OBJECTIVE: To present the final 36-month efficacy and safety results from DUOGLOBE (DUOdopa/Duopa in Patients with Advanced Parkinson's Disease - a GLobal OBservational Study Evaluating Long-Term Effectiveness; NCT02611713). METHODS: DUOGLOBE was an international, prospective, long-term, real-world, observational study of patients with aPD initiating LCIG in routine clinical care. The primary endpoint was change in patient-reported "Off" time to Month 36. Safety was assessed by monitoring serious adverse events (SAEs). RESULTS: Significant improvements in "Off" time were maintained over 3 years (mean [SD]: -3.3 hours [3.7]; p < 0.001). There were significant improvements to Month 36 in total scores of the Unified Dyskinesia Rating Scale (-5.9 [23.7]; p = 0.044), Non-Motor Symptoms Scale (-14.3 [40.5]; p = 0.002), Parkinson's Disease Sleep Scale-2 (-5.8 [12.9]; p < 0.001), and Epworth Sleepiness Scale (-1.8 [6.0]; p = 0.008). Health-related quality of life and caregiver burden significantly improved through Months 24 and 30, respectively (Month 24, 8-item Parkinson's Disease Questionnaire Summary Index, -6.0 [22.5]; p = 0.006; Month 30, Modified Caregiver Strain Index, -2.3 [7.6]; p = 0.026). Safety was consistent with the well-established LCIG profile (SAEs: 54.9% of patients; discontinuations: 54.4%; discontinuations due to an adverse event: 27.2%). Of 106 study discontinuations, 32 patients (30.2%) continued LCIG outside the study. CONCLUSION: DUOGLOBE demonstrates real-world, long-term, reductions in motor and non-motor symptoms in patients with aPD treated with LCIG.

Levodopa/carbidopa intestinal gel via percutaneous endoscopic transgastric jejunostomy in advanced Parkinson's disease: hitting two birds with one stone?

Here we focus on people with advanced PD undergoing percutaneous endoscopic transgastric jejunostomy (PEG-J) ("one stone") for LCIG infusion therapy for managing severe motor fluctuations ("first bird") and discuss its implications for improving accompanying symptoms of cardiovascular, urinary, and gastrointestinal autonomic failure ("second bird").

Age at Onset Influences Progression of Motor and Non-Motor Symptoms during the Early Stage of Parkinson's Disease: A Monocentric Retrospective Study.

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.

Monoamine-oxidase Type B Inhibitors and Cognitive Functions in Parkinson's Disease: Beyond the Primary Mechanism of Action.

Symptoms of cognitive impairment are rather common since the early stage of Parkinson's disease (PD); they aggravate with disease progression and may lead to dementia in a significant proportion of cases. Worsening of cognitive symptoms in PD patients depends on the progression of subcortical dopaminergic damage as well as the involvement of other brain neurotransmitter systems in cortical and subcortical regions. Beyond the negative impact on disability and quality of life, the presence and severity of cognitive symptoms may limit adjustments of dopamine replacement therapy along the disease course. This review focuses on the consequences of the administration of monoamine-oxidase type Binhibitors (MAOB-I) on cognition in PD patients. Two drugs (selegiline and rasagiline) are available for the treatment of motor symptoms of PD as monotherapy or in combination with L-DOPA or dopamine agonists in stable and fluctuating patients; a further drug (safinamide) is usable in fluctuating subjects solely. The results of available studies indicate differential effects according to disease stage and drug features. In early, non-fluctuating patients, selegiline and rasagiline ameliorated prefrontal executive functions, similarly to other dopaminergic drugs. Benefit on some executive functions was maintained in more advanced, fluctuating patients, despite the tendency of worsening prefrontal inhibitory control activity. Interestingly, high-dose safinamide improved inhibitory control in fluctuating patients. The benefit of high-dose safinamide on prefrontal inhibitory control mechanisms may stem from its dual mechanism of action, allowing reduction of excessive glutamatergic transmission, in turn secondary to increased cortical dopaminergic input.

Cognitive dual-task cost depends on the complexity of the cognitive task, but not on age and disease.

Introduction: Dual-tasking (DT) while walking is common in daily life and can affect both gait and cognitive performance depending on age, attention prioritization, task complexity and medical condition. The aim of the present study was to investigate the effects of DT on cognitive DT cost (DTC) (i) in a dataset including participants of different age groups, with different neurological disorders and chronic low-back pain (cLBP) (ii) at different levels of cognitive task complexity, and (iii) in the context of a setting relevant to daily life, such as combined straight walking and turning. Materials and methods: Ninety-one participants including healthy younger and older participants and patients with Parkinson's disease, Multiple Sclerosis, Stroke and cLBP performed a simple reaction time (SRT) task and three numerical Stroop tasks under the conditions congruent (StC), neutral (StN) and incongruent (StI). The tasks were performed both standing (single task, ST) and walking (DT), and DTC was calculated. Mixed ANOVAs were used to determine the effect of group and task complexity on cognitive DTC. Results: A longer response time in DT than in ST was observed during SRT. However, the response time was shorter in DT during StI. DTC decreased with increasing complexity of the cognitive task. There was no significant effect of age and group on cognitive DTC. Conclusion: Our results suggest that regardless of age and disease group, simple cognitive tasks show the largest and most stable cognitive effects during DT. This may be relevant to the design of future observational studies, clinical trials and for clinical routine.

The impact of cerebral vasomotor reactivity on cerebrovascular diseases and cognitive impairment.

The regulation of cerebral blood flow (CBF) is a complex and tightly controlled function ensuring delivery of oxygen and nutrients and removal of metabolic wastes from brain tissue. Cerebral vasoreactivity (CVR) refers to the ability of the nervous system to regulate CBF according to metabolic demands or changes in the microenvironment. This can be assessed through a variety of nuclear medicine and imaging techniques and protocols. Several studies have investigated the association of CVR with physiological and pathological conditions, with particular reference to the relationship with cognitive impairment and cerebrovascular disorders (CVD). A better understanding of the interaction between CVR and cognitive dysfunction in chronic and particularly acute CVD could help improving treatment and rehabilitation strategies in these patients. In this paper, we reviewed current knowledge on CVR alterations in the context of acute and chronic CVD and cognitive dysfunction. Alterations in CVR and hemodynamics have been described in patients with both neurodegenerative and vascular cognitive impairment, and the severity of these alterations seems to correlate with CVR derailment. Furthermore, an increased risk of cognitive impairment progression has been associated with alterations in CVR parameters and hemodynamics. Few studies have investigated these associations in acute cerebrovascular disorders and the results are inconsistent; thus, further research on this topic is encouraged.

Feasibility, Safety, and Effectiveness of Telerehabilitation in Mild-to-Moderate Parkinson's Disease.

Introduction: Parkinson's disease (PD) patients frequently engage in rehabilitation to ameliorate symptoms. During the Coronavirus disease 2019 (COVID-19) pandemic, access to rehabilitation programs has been markedly limited, consequently, telerehabilitation gained popularity. In this prospective, open-label, and pilot study, we aimed to investigate feasibility, safety, and efficacy of telerehabilitation in mild-to-moderate PD patients. Materials and Methods: Twenty-three PD patients, with Hoehn and Yahr stage <3, without gait disturbances or dementia and capable of using the televisit platform, were recruited for a 5-week telerehabilitation program, consisting of 1 remote visit with a therapist and a minimum of two sessions of >30-min of self-conducted exercises per week. Patients received video tutorials of exercises and were asked to keep a diary of sessions. At baseline (T0), at the end of the intervention (T1), and 1 month after the end of treatment (T2), patients were remotely assessed with MDS-UPDRS part I-III, PDQ-39, Functional Independence Measure (FIM), and Frontal Assessment Battery scales, respectively. Acceptable compliance to the program was defined as >60% matching of frequency and duration of sessions, whereas optimal compliance was set at >80% matching. Results: The dropout rate was 0%. Over 85% of patients reached acceptable adherence cut-off and around 70% reached optimal one. No adverse events were reported during sessions. The repeated measure analysis of variance (rANOVA) showed a significant effect of factor "time" for MDS-UPDRS-III (p < 0.0001) with a mean reduction of 4.217 points between T0 and T1 and return to baseline at T2. No significant effect was found for other outcome measures. Conclusion: Our findings demonstrate that telerehabilitation is safe, feasible, and effective on motor symptoms in mild-to-moderate PD patients.

Outcomes Impacting Quality of Life in Advanced Parkinson's Disease Patients Treated with Levodopa-Carbidopa Intestinal Gel.

BACKGROUND: It is believed that motor symptoms, including dyskinesia, and non-motor symptoms impact health-related quality of life (HRQoL) in patients with Parkinson's disease (PD), and that improvements in these metrics are correlated. OBJECTIVE: Investigate the relationship between HRQoL and measures of PD severity and treatment efficacy, including motor and non-motor symptoms. METHODS: This was a planned investigation of an international, prospective, single-arm, post-marketing observational study of the long-term effectiveness of levodopa-carbidopa intestinal gel (LCIG) in patients with advanced PD. Pearson correlation coefficients (PCC) were calculated for baseline and change from baseline at 12 months between HRQoL and motor and non-motor symptoms. RESULTS: A total of 195 patients were included. At baseline, HRQoL was moderately positively correlated with Activities of Daily Living (UPDRS II, PCC = 0.44), non-motor symptoms (0.48), and measures of sleep (0.50 and 0.40); all p < 0.001. After 12 months of treatment with LCIG, improvements in HRQoL were moderately positively correlated with improvement from baseline in non-motor symptoms (PCC = 0.42), sleep (0.54), and daytime sleepiness (0.40; all p < 0.001), and weakly correlated with improvement in dyskinesia signs and symptoms (PCC = 0.23; p = 0.011). Improvement in HRQoL was not correlated with improvements in OFF time or dyskinesia time. CONCLUSION: Both at baseline and for change from baseline at 12 months, HRQoL was correlated with baseline and change from baseline in dyskinesia, Activities of Daily Living, and non-motor symptoms, including sleep; but not with baseline or change in OFF time.

Step-Counting Accuracy of a Commercial Smartwatch in Mild-to-Moderate PD Patients and Effect of Spatiotemporal Gait Parameters, Laterality of Symptoms, Pharmacological State, and Clinical Variables.

Commercial smartwatches could be useful for step counting and monitoring ambulatory activity. However, in Parkinson's disease (PD) patients, an altered gait, pharmacological condition, and symptoms lateralization may affect their accuracy and potential usefulness in research and clinical routine. Steps were counted during a 6 min walk in 47 patients with PD and 47 healthy subjects (HS) wearing a Garmin Vivosmart 4 (GV4) on each wrist. Manual step counting was used as a reference. An inertial sensor (BTS G-Walk), placed on the lower back, was used to compute spatial-temporal gait parameters. Intraclass correlation coefficient (ICC) and mean absolute percentage error (MAPE) were used for accuracy evaluation and the Spearman test was used to assess the correlations between variables. The GV4 overestimated steps in PD patients with only a poor-to-moderate agreement. The OFF pharmacological state and wearing the device on the most-affected body side led to an unacceptable accuracy. The GV4 showed an excellent agreement and MAPE in HS at a self-selected speed, but an unacceptable performance at a slow speed. In PD patients, MAPE was not associated with gait parameters and clinical variables. The accuracy of commercial smartwatches for monitoring step counting might be reduced in PD patients and further influenced by the pharmacological condition and placement of the device.

DUOGLOBE: One-Year Outcomes in a Real-World Study of Levodopa Carbidopa Intestinal Gel for Parkinson's Disease.

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) is an established treatment for improving motor and some non-motor symptoms (NMS) in patients with advanced Parkinson's disease (PD). Prospective long-term data in routine clinical practice are limited. OBJECTIVE: Assess LCIG effectiveness and safety in patients with advanced PD after 12 months during real-world routine clinical practice. METHODS: Duodopa/Duopa in patients with advanced Parkinson's disease-a global observational study evaluating long-term effectiveness (DUOGLOBE) (NCT02611713) is an ongoing, prospective, multinational, observational study of LCIG-naïve patients treated as part of routine clinical practice; 3 years of follow-up are planned. The primary outcome is the change in patient-reported off time. Other assessments include the Unified Dyskinesia Rating Scale (UDysRS), Non-Motor Symptoms Scale (NMSS), Parkinson's Disease Sleep scale (PDSS-2), Epworth Sleepiness Scale (ESS), health-related quality of life (HR-QoL), caregiver burden, and serious adverse events (SAEs). Outcomes from baseline to month (M) 12 are presented. RESULTS: In this 12-month follow-up, patients (N = 195) had baseline characteristics similar to other LCIG studies. Significant improvements (mean change to M12) were observed in off time (-3.9 ± 3.6 hr/day, P < 0.001), dyskinesia assessed using the UDysRS (-9.6 ± 22.5, P < 0.001), NMSS (-23.1 ± 41.4, P < 0.001), sleep and sleepiness symptoms on the PDSS-2 (-6.5 ± 12.2, P < 0.001) and ESS (-1.0 ± 5.7, P < 0.05), HR-QoL (-9.0 ± 21.6, P < 0.001), and caregiver burden (-1.9 ± 6.7, P = 0.008). Overall, 40.5% (n = 79) of patients experienced SAEs; fall (n = 6; 3.1%) and urinary tract infection (n = 6; 3.1%) were SAEs reported in ≥3% of patients. CONCLUSIONS: These 12-month outcome data show sustained, long-term improvements and support the real-world effectiveness of LCIG in patients with advanced PD. Safety was consistent with previous studies.

Immune System and Neuroinflammation in Idiopathic Parkinson's Disease: Association Analysis of Genetic Variants and miRNAs Interactions.

The present study investigated the association of SNPs involved in the regulation of immune response, cellular degenerative and neuroinflammatory pathways with the susceptibility and progression of idiopathic Parkinson's Disease (PD). In particular, 342 PD patients were subjected to a genotyping analysis of a panel of 120 SNPs by Open Array Technology. As control group, 503 samples representative of the European general population were utilized. The genetic analysis identified 26 SNPs associated with PD susceptibility. Of them, 12 SNPs were described as significant expression Quantitative Loci (eQTL) variants in different brain regions associated with motor and non-motor PD phenomenology. Moreover, the study highlighted 11 novel susceptibility genes for PD, which may alter multiple signaling pathways critically involved in peripheral immune response, neuroinflammation, neurodegeneration and dopaminergic neurons wiring. The study of miRNA-target genes highlighted a possible role of miR-499a, miR-196a2, and miR-29a in the modulation of multiple neuroinflammatory and neurodegenerative mechanisms underlying PD physiopathology. The study described a network of interconnected genes (APOE, CLU, IL6, IL7R, IL12B, INPP5D, MAPK1, MEF2C, MIF, and TNFSF14), which may act as upstream regulators in the modulation of biological pathways relevant to PD. Intriguingly, IL6 stands out as a master gene regulator since it may indirectly regulate the network of interconnected genes. The study highlighted different genes and miRNAs interactions potentially involved in PD physiopathology, which are worth to be further explored to improve the knowledge of disease and the research of novel treatments strategies.

Switch from rasagiline to safinamide in fluctuating Parkinson's disease patients: a retrospective, pilot study.

Besides the inhibition of monoamine-oxidase-B, high-dose safinamide (100 mg) also blocks voltage-gated Na+ and Ca++ channels and inhibits glutamate release at overactive synapses. This latter mechanism may provide further benefit to fluctuating Parkinson's disease (PD) patients compared to rasagiline. Here, we retrospectively investigated the consequences of shifting from rasagiline to high-dose safinamide in PD patients reporting symptoms of wearing-off, defined by the Wearing-Off-Questionnaire-19 (WOQ-19) score ≥3 at baseline. Seventeen PD patients were switched from rasagiline 1 mg to safinamide 100 mg because of the report of symptoms of fluctuations while under therapy with either levodopa+rasagiline or levodopa+rasagiline+dopamine agonists, or re-occurrence of fluctuations previously corrected by add-on with rasagiline. Patients were re-evaluated 4-6 months after switch. Switch to safinamide 100 mg produced benefit in 9/17 (52.9%) subjects, together with significant reduction of subjective symptoms of wearing-off. There was no report of adverse events. Findings from this retrospective, exploratory study suggest that safinamide 100 mg may produce more powerful benefit that rasagiline 1 mg as add-on to levodopa in fluctuating PD patients, possibly because of the bimodal mechanism of action of the former drug.

Cognitive and Neuropsychiatric Profiles in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson's Disease.

A bstract : Rapid eye movement (REM) sleep behavior disorder (RBD) is a risk factor for developing Parkinson's disease (PD) and may represent its prodromal state. We compared neuropsychological and neuropsychiatric phenotypes of idiopathic (i) RBD, PD and healthy comparators (HC) in order to identify iRBD specific characteristics. Thirty-eight patients with iRBD, 38 PD patients with RBD (PD + RBD), 38 PD patients without RBD (PD-RBD) and 38 HC underwent a comprehensive neurological, neuropsychological and neuropsychiatric evaluation. iRBD, PD + RBD and PD-RBD performed worse than HC in short-term verbal memory, praxia, language and executive functions. iRBD had higher levels of anxiety, depression, apathy and alexithymia than HC. iRBD had higher levels of apathy than PD + RBD. Both PD groups had higher levels of anxiety and depression than HC. Surprisingly, iRBD performed better than all groups in long-term verbal memory. Patients diagnosed with iRBD are characterized by poor global cognitive performance, but better long-term memory and higher levels of depression, anxiety, alexithymia and apathy. Alexithymia and apathy in patients diagnosed with iRBD may be the expression of precocious derangement of emotional regulation, subsequently observed also in PD. Cognitive and neuropsychiatric symptoms of iRBD are early clinical manifestations of widespread neurodegeneration.

Safinamide improves executive functions in fluctuating Parkinson's disease patients: an exploratory study.

Safinamide is a monoamine-oxidase-B inhibitor with peculiar features. At the dose of 100 mg/day, safinamide stimulates dopaminergic transmission and reduces glutamatergic transmission. Here, we investigated the effects of safinamide 100 mg on executive functions at the end of levodopa dose in fluctuating Parkinson's disease (PD) patients. Thirty-two fluctuating PD patients were submitted at baseline (V1) to the UPDRS-III, the Frontal Assessment Battery (FAB) and the Stroop-Word-Color-Test (SWCT) at the end of levodopa dose. Safinamide was then added to the original therapy. After 12 weeks of treatment, patients underwent the final visit (V2), including the UPDRS-III, the FAB and the SWCT with the same daily time schedule as V1. Treatment with safinamide was associated with significant increases of the total FAB score, SWCT-interference time score and UPDRS-III score. Within FAB subdomains, add-on with safinamide significantly increased motor programming and increased mental flexibility and inhibitory control scores. The results of this exploratory study show that add-on with safinamide improves executive functions at the end of levodopa dose in fluctuating PD patients. In particular, attention and inhibition of cognitive interference were significantly ameliorated by add-on with safinamide, suggesting increased modulatory performances of prefrontal cortical pathways. If confirmed by future research on larger cohorts and under controlled conditions, the present results may represent the basis for a novel indication for the use of safinamide in fluctuating PD patients.

The tolerability, safety and efficacy of safinamide in elderly Parkinson's disease patients: a retrospective study.

Safinamide (SF) is a third-generation monoamine-oxidase-B inhibitor that proved efficacy as add-on to levodopa in fluctuating Parkinson's disease (PD) patients. Despite the high prevalence of complicated PD in older population, the data on the tolerability, safety and efficacy of SF in elderly patients are rather poor. Here we studied retrospectively the consequences of add-on with SF in PD patients older than 65 years. Fifty-three fluctuating PD patients were included (30 subjects aged between 65 and 75 years, the remaining 23 subjects aged > 75 years). Patients were treated with either 50 (n = 27) or 100 mg (n = 26) SF for at least 6 months. In all patients, fluctuations were identified by the report of a Wearing-Off-Questionnaire-19 (WOQ-19) score ≥ 3 at baseline. Add-on with SF was well tolerated and safe. Adverse events occurred in 30% of patients and led to drug discontinuation in 11% of cases. At follow-up visits, 60% of patients reported lowering of the WOQ-19 score to ≤ 2. There were no significant differences related to age or daily drug dose in tolerability, safety or efficacy. The results of this study provide evidence of the efficacy, tolerability and safety of SF in elderly PD patients.