Intra and inter-rater remote assessment of bradykinesia in Parkinson's disease.

INTRODUCTION: Reliable assessment of individuals with Parkinson's disease (PD) is essential for providing adequate treatment. Clinical assessment is a complex and time-consuming task, especially for bradykinesia, since its evaluation can be influenced by the degree of experience of the examiner, patient collaboration and individual bias. Improvement of the clinical evaluation can be obtained by considering assessments from several professionals. However, this is only true when inter and intra-rater agreement are high. Recently, the Movement Disorder Society highlighted, during the COVID-19 pandemic, the need to develop and validate technologies for remote assessment of the motor status of people with PD. Thus, this study introduces an objective strategy for the remote evaluation of bradykinesia using multi-specialist analysis. METHODS: Twelve volunteers with PD participated and these were asked to execute finger tapping, hand opening/closing and pronation/supination movements. Each task was recorded and rated by fourteen PD health experts for each patient. The scores were assessed on an individual basis. Intra and inter-rater agreement and correlation were estimated. RESULTS: The results showed that agreements and correlations between experienced examiners were high with low variability. In addition, group analysis was noted as possessing the potential to solve individual inconsistency bias. CONCLUSION: Furthermore, this study demonstrated the need for a group with prior training and experience, along with indicating the importance for the development of a clinical protocol that can use telemedicine for the evaluation of individuals with PD, as well as the inclusion of a specialized mediating group. In Addition, this research helps to the development of a valid remote assessment of bradykinesia.

Sleep and Overactive Bladder in Parkinson's Disease.

Patients with Parkinson's disease (PD) have disturbances in their bladder and sleep physiology that lead to nocturia and overactive bladder (OAB). These symptoms can be extremely bothersome and impact not only their quality of life (QoL) but also the QoL of their caretakers. We aim to highlight the changes in bladder and sleep physiology in PD and explore OAB/nocturia treatment strategies in this population.

Nicotine restores olfactory function by activation of prok2R/Akt/FoxO3a axis in Parkinson's disease.

BACKGROUND: Olfactory dysfunction occurs frequently in Parkinson's disease (PD). In this study, we aimed to explore the potential biomarkers and underlying molecular pathways of nicotine for the treatment of olfactory dysfunction in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. METHODS: MPTP was introduced into C57BL/6 male mice to generate a PD model. Regarding in vivo experiments, we performed behavioral tests to estimate the protective effects of nicotine in MPTP-induced PD mice. RNA sequencing and traditional molecular methods were used to identify molecules, pathways, and biological processes in the olfactory bulb of PD mouse models. Then, in vitro experiments were conducted to evaluate whether nicotine can activate the prok2R/Akt/FoxO3a signaling pathway in both HEK293T cell lines and primary olfactory neurons treated with 1-methyl-4-phenylpyridinium (MPP+). Next, prok2R overexpression (prok2R+) and knockdown (prok2R-) were introduced with lentivirus, and the Akt/FoxO3a signaling pathway was further explored. Finally, the damaging effects of MPP+ were evaluated in prok2R overexpression (prok2R+) HEK293T cell lines. RESULTS: Nicotine intervention significantly alleviated olfactory and motor dysfunctions in mice with PD. The prok2R/Akt/FoxO3a signaling pathway was activated after nicotine treatment. Consequently, apoptosis of olfactory sensory neurons was significantly reduced. Furthermore, prok2R+ and prok2R- HEK293T cell lines exhibited upregulation and downregulation of the Akt/FoxO3a signaling pathway, respectively. Additionally, prok2R+ HEK293T cells were resistant to MPP+-induced apoptosis. CONCLUSIONS: This study showed the effectiveness and underlying mechanisms of nicotine in improving hyposmia in PD mice. These improvements were correlated with reduced apoptosis of olfactory sensory neurons via activated prok2R/Akt/FoxO3a axis. These results explained the potential protective functions of nicotine in PD patients.

Spontaneous brain activity in the hippocampal regions could characterize cognitive impairment in patients with Parkinson's disease.

OBJECTIVE: This study aimed to investigate whether spontaneous brain activity can be used as a prospective indicator to identify cognitive impairment in patients with Parkinson's disease (PD). METHODS: Resting-state functional magnetic resonance imaging (RS-fMRI) was performed on PD patients. The cognitive level of patients was assessed by the Montreal Cognitive Assessment (MoCA) scale. The fractional amplitude of low-frequency fluctuation (fALFF) was applied to measure the strength of spontaneous brain activity. Correlation analysis and between-group comparisons of fMRI data were conducted using Rest 1.8. By overlaying cognitively characterized brain regions and defining regions of interest (ROIs) based on their spatial distribution for subsequent cognitive stratification studies. RESULTS: A total of 58 PD patients were enrolled in this study. They were divided into three groups: normal cognition (NC) group (27 patients, average MoCA was 27.96), mild cognitive impairment (MCI) group (21 patients, average MoCA was 23.52), and severe cognitive impairment (SCI) group (10 patients, average MoCA was 17.3). It is noteworthy to mention that those within the SCI group exhibited the most advanced chronological age, with an average of 74.4 years, whereas the MCI group displayed a higher prevalence of male participants at 85.7%. It was found hippocampal regions were a stable representative brain region of cognition according to the correlation analysis between the fALFF of the whole brain and cognition, and the comparison of fALFF between different cognitive groups. The parahippocampal gyrus was the only region with statistically significant differences in fALFF among the three cognitive groups, and it was also the only brain region to identify MCI from NC, with an AUC of 0.673. The paracentral lobule, postcentral gyrus was the region that identified SCI from NC, with an AUC of 0.941. The midbrain, hippocampus, and parahippocampa gyrus was the region that identified SCI from MCI, with an AUC of 0.926. CONCLUSION: The parahippocampal gyrus was the potential brain region for recognizing cognitive impairment in PD, specifically for identifying MCI. Thus, the fALFF of parahippocampal gyrus is expected to contribute to future study as a multimodal fingerprint for early warning.

Whole brain pattern of iron accumulation in REM sleep behavior disorder.

Isolated REM sleep behavior disorder (iRBD) is an early stage of synucleinopathy with most patients progressing to Parkinson's disease (PD) or related conditions. Quantitative susceptibility mapping (QSM) in PD has identified pathological iron accumulation in the substantia nigra (SN) and variably also in basal ganglia and cortex. Analyzing whole-brain QSM across iRBD, PD, and healthy controls (HC) may help to ascertain the extent of neurodegeneration in prodromal synucleinopathy. 70 de novo PD patients, 70 iRBD patients, and 60 HCs underwent 3 T MRI. T1 and susceptibility-weighted images were acquired and processed to space standardized QSM. Voxel-based analyses of grey matter magnetic susceptibility differences comparing all groups were performed on the whole brain and upper brainstem levels with the statistical threshold set at family-wise error-corrected p-values <.05. Whole-brain analysis showed increased susceptibility in the bilateral fronto-parietal cortex of iRBD patients compared to both PD and HC. This was not associated with cortical thinning according to the cortical thickness analysis. Compared to iRBD, PD patients had increased susceptibility in the left amygdala and hippocampal region. Upper brainstem analysis revealed increased susceptibility within the bilateral SN for both PD and iRBD compared to HC; changes were located predominantly in nigrosome 1 in the former and nigrosome 2 in the latter group. In the iRBD group, abnormal dopamine transporter SPECT was associated with increased susceptibility in nigrosome 1. iRBD patients display greater fronto-parietal cortex involvement than incidental early-stage PD cohort indicating more widespread subclinical neuropathology. Dopaminergic degeneration in the substantia nigra is paralleled by susceptibility increase, mainly in nigrosome 1.

On the Optimal Diagnosis and the Evolving Role of Pimavanserin in Parkinson's Disease Psychosis.

Parkinson's disease (PD) is associated with the development of psychosis (PDP), including hallucinations and delusions, in more than half of the patient population. Optimal PD management must therefore involve considerations about both motor and non-motor symptoms. Often, clinicians fail to diagnosis psychosis in patients with PD and, when it is recognized, treat it suboptimally, despite the availability of multiple interventions. In this paper, we provide a summary of the current guidelines and clinical evidence for treating PDP with antipsychotics. We also provide recommendations for diagnosis and follow-up. Finally, an updated treatment algorithm for PDP that incorporates the use of pimavanserin, the only US FDA-approved drug for the treatment of PDP, was developed by extrapolating from a limited evidence base to bridge to clinical practice using expert opinion and experience. Because pimavanserin is only approved for the treatment of PDP in the US, in other parts of the world other recommendations and algorithms must be considered.

A Delphi Panel of People With Parkinson's Disease Regarding Responsibility: Toward a Preliminary Taxonomy.

IMPORTANCE: A sense of agency is associated with complex occupation-related responsibilities. A taxonomy can guide clinicians in enhancing responsibility in patients with Parkinson's disease (PwPD). OBJECTIVE: To (1) discover levels of responsibility in occupations for PwPD and (2) propose a taxonomy for occupations. DESIGN: A two-round Delphi study with PwPD and a one-round Delphi study with international experts. SETTING: Electronic survey. PARTICIPANTS: PwPD (N = 75) and international experts (N = 8). OUTCOMES AND MEASURES: PwPD expressed their levels of an inherent sense of responsibility for each occupation (1 = very low responsibility, 5 = very high responsibility). International experts rated their level of agreement (5 = strongly agree, 1 = strongly disagree) with each dimension of the taxonomy. A consensus was determined to have been reached if the interquartile range was ≤1 and 70% agreement in two adjacent categories was achieved. RESULTS: Thirty-three occupation categories were deemed as having very high to moderate responsibility for PwPD. Consequences of actions and the presence of others made up the two-dimensional responsibility taxonomy. Occupations have more challenging responsibility characteristics when they are performed with free choice, a level of high physical effort, alone, and with moral consequences. CONCLUSIONS AND RELEVANCE: This study yielded the first consensus among PwPD regarding responsibility in occupations as well as a classification system for charting the complexity of responsibility in occupations. The occupation list we have created can be beneficial to health care professionals when providing interventions or conducting outcome assessments. Plain-Language Summary: When planning interventions for patients with Parkinson's disease, it can be helpful for clinicians to be aware of patients' perspectives regarding their sense of responsibility to perform occupations. The use of a systematic sequence of challenging occupations with responsibility attributes ranging from less complex to more complex can help enhance patient occupational participation.

Transcranial alternating current stimulation improves quality of life in Parkinson's disease: study protocol for a randomized, double-blind, controlled trial.

BACKGROUND: The neural cells in the brains of patients with Parkinson's disease (PWP) display aberrant synchronized oscillatory activity within the beta frequency range. Additionally, enhanced gamma oscillations may serve as a compensatory mechanism for motor inhibition mediated by beta activity and also reinstate plasticity in the primary motor cortex affected by Parkinson's disease. Transcranial alternating current stimulation (tACS) can synchronize endogenous oscillations with exogenous rhythms, thereby modulating cortical activity. The objective of this study is to investigate whether the addition of tACS to multidisciplinary intensive rehabilitation treatment (MIRT) can improve symptoms of PWP so as to enhance the quality of life in individuals with Parkinson's disease based on the central-peripheral-central theory. METHODS: The present study was a randomized, double-blind trial that enrolled 60 individuals with Parkinson's disease aged between 45 and 70 years, who had Hoehn-Yahr scale scores ranging from 1 to 3. Participants were randomly assigned in a 1:1 ratio to either the tACS + MIRT group or the sham-tACS + MIRT group. The trial consisted of a two-week double-blind treatment period followed by a 24-week follow-up period, resulting in a total duration of twenty-six weeks. The primary outcome measured the change in PDQ-39 scores from baseline (T0) to 4 weeks (T2), 12 weeks (T3), and 24 weeks (T4) after completion of the intervention. The secondary outcome assessed changes in MDS-UPDRS III scores at T0, the end of intervention (T1), T2, T3, and T4. Additional clinical assessments and mechanistic studies were conducted as tertiary outcomes. DISCUSSION: The objective of this study is to demonstrate that tACS can enhance overall functionality and improve quality of life in PWP, based on the framework of MIRT. Additionally, it seeks to establish a potential correlation between these therapeutic effects and neuroplasticity alterations in relevant brain regions. The efficacy of tACS will be assessed during the follow-up period in order to optimize neuroplasticity and enhance its potential impact on rehabilitation efficiency for PWP. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300071969. Registered on 30 May 2023.

The effects of standard and modified LSVT BIG therapy protocols on balance and gait in Parkinson's disease: A randomized controlled trial.

BACKGROUND: Lee Silverman voice treatment (LSVT) BIG is an exercise program developed for patients with Parkinson's disease (PwPD), consisting of sets of exercises performed for 4 consecutive days a week for 4 weeks. However, the standard protocol suggests a treatment frequency difficult to follow for most patients who have difficulties reaching rehabilitation clinics. Our aim was to compare the standard LSVT BIG protocol with a modified LSVT (m-LSVT) BIG protocol (twice a week in the clinic for 4 weeks and twice a week at home for 4 weeks). METHODS: In this randomized controlled trial, 16 PwPD (aged 18-80 years, Hoehn and Yahr stages I-III) were recruited into two groups. The LSVT group received standard LSVT BIG training (four times per week for 4 weeks at the clinic). The other group was given m-LSVT BIG exercises, but unlike the LSVT group, the m-LSVT group exercised twice a week at the clinic and twice a week at home for 4 weeks. The Berg Balance Scale was used to assess functional balance. Biodex Balance System was used to assess laboratory balance measures. Timed Up and Go test and G-Walk sensor system were used to assess functional mobility and spatiotemporal gait analysis. RESULTS: Significant group-by-time interactions on the eyes open-firm surface score of the modified clinical test of sensory integration of balance (F = 10.138, p = .007) and gait cycle symmetry index (F = 10.470, p = .010) were found to be in favor of the LSVT group. Additionally, post hoc analyses revealed that both groups significantly improved postural stability, gait speed, motor symptoms, and functional mobility (p < .05). CONCLUSION: The results revealed the beneficial effects of the modified protocol on balance and gait in PwPD, as well as the superiority of the standard LSVT BIG protocol. The m-LSVT BIG protocol may be an effective intervention method, especially for PwPD who have difficulty adapting to the treatment frequency of the standard protocol.

Diagnostic value of vietnamese smell identification test in Parkinson's disease.

INTRODUCTION: The Vietnamese Smell Identification Test (VSIT) has been validated in determining olfactory dysfunction in the Vietnamese population; however, its value in diagnosing Parkinson's disease (PD) has not been established. METHODS: This case-control study was conducted at University Medical Center HCMC, Ho Chi Minh City, Vietnam. The study sample included non-demented PD patients and healthy controls (HC) who were gender- and age-matched. All participants were evaluated for odor identification ability using the VSIT and the Brief Smell Identification Test (BSIT). RESULTS: A total of 218 HCs and 218 PD patients participated in the study. The median VSIT and BSIT scores were significantly different between PD and HC groups (VSIT, 5 (3) vs. 9 (2), P < 0.0001; BSIT, 6 (3) vs 8 (2), P < 0.0001). Using the cut-off of <8 for correct answers out of 12 odorants, the VSIT had higher sensitivity (84.4%) and specificity (86.2%) than those of the BSIT (sensitivity of 81.7% and specificity of 69.3%) for the diagnosis of PD. The area under the curve (AUC) value was greater for the VSIT than for the BSIT (0.909 vs 0.818). The smell identification scores were not significantly correlated with disease duration, disease severity, or LEDD (all p > 0.05). CONCLUSION: The VSIT can be a valuable ancillary tool for supporting the diagnosis of PD in Vietnam. Olfactory dysfunction in PD was unrelated to the disease duration and severity. The VSIT can be applied to improve the accuracy of clinical PD diagnosis.

Neural Oscillations and Functional Significances for Prioritizing Dual-Task Walking in Parkinson's Disease.

Background: Task prioritization involves allocating brain resources in a dual-task scenario, but the mechanistic details of how prioritization strategies affect dual-task walking performance for Parkinson's disease (PD) are little understood. Objective: We investigated the performance benefits and corresponding neural signatures for people with PD during dual-task walking, using gait-prioritization (GP) and manual-prioritization (MP) strategies. Methods: Participants (N = 34) were asked to hold two inter-locking rings while walking and to prioritize either taking big steps (GP strategy) or separating the two rings (MP strategy). Gait parameters and ring-touch time were measured, and scalp electroencephalograph was performed. Results: Compared with the MP strategy, the GP strategy yielded faster walking speed and longer step length, whereas ring-touch time did not significantly differ between the two strategies. The MP strategy led to higher alpha (8-12 Hz) power in the posterior cortex and beta (13-35 Hz) power in the left frontal-temporal area, but the GP strategy was associated with stronger network connectivity in the beta band. Changes in walking speed and step length because of prioritization negatively correlated with changes in alpha power. Prioritization-related changes in ring-touch time correlated negatively with changes in beta power but positively with changes in beta network connectivity. Conclusions: A GP strategy in dual-task walking for PD can enhance walking speed and step length without compromising performance in a secondary manual task. This strategy augments attentional focus and facilitates compensatory reinforcement of inter-regional information exchange.

Corpus callosum and cerebellum participate in semantic dysfunction of Parkinson's disease: a diffusion tensor imaging-based cross-sectional study.

Language dysfunction is common in Parkinson's disease (PD) patients, among which, the decline of semantic fluency is usually observed. This study aims to explore the relationship between white matter (WM) alterations and semantic fluency changes in PD patients. 127 PD patients from the Parkinson's Progression Markers Initiative cohort who received diffusion tensor imaging scanning, clinical assessment and semantic fluency test (SFT) were included. Tract-based special statistics, automated fiber quantification, graph-theoretical and network-based analyses were performed to analyze the correlation between WM structural changes, brain network features and semantic fluency in PD patients. Fractional anisotropy of corpus callosum, anterior thalamic radiation, inferior front-occipital fasciculus, and uncinate fasciculus, were positively correlated with SFT scores, while a negative correlation was identified between radial diffusion of the corpus callosum, inferior longitudinal fasciculus, and SFT scores. Automatic fiber quantification identified similar alterations with more details in these WM tracts. Brain network analysis positively correlated SFT scores with nodal efficiency of cerebellar lobule VIII, and nodal local efficiency of cerebellar lobule X. WM integrity and myelin integrity in the corpus callosum and several other language-related WM tracts may influence the semantic function in PD patients. Damage to the cerebellum lobule VIII and lobule X may also be involved in semantic dysfunction in PD patients.

Efficacy of acupuncture (Jin's three-needle) on motor symptoms and anxiety in patients with Parkinson's disease: protocol for a multicentre, randomised, assessor-blinded clinical trial.

INTRODUCTION: Parkinson's disease (PD) has a significant impact on a substantial number of individuals in China. Notably, 31% of patients with PD also grapple with the additional burden of anxiety. This dual challenge of managing both PD and anxiety underscores the complexity of the condition and the diverse range of symptoms patients may experience. Considering the circumstances, the cost and potential drawbacks associated with traditional antiparkinsonian drugs become increasingly relevant. Acupuncture emerges as a significant non-pharmacological adjunct therapy. Offering a potentially safer and more cost-effective option, acupuncture addresses the pressing need for holistic and complementary treatments that may alleviate both the motor symptoms of PD and the accompanying anxiety. METHODS AND ANALYSIS: This is a multicentre, randomised controlled and assessor-blind trial. A total of 210 eligible patients with PD will be randomly assigned (1:1) to Jin's three-needle (JTN) acupuncture group or waitlist (WL) group. Patients in the JTN group will receive acupuncture therapy three times per week for 4 weeks. Patients in the WL group will maintain their original dosage of antiparkinsonian drugs and receive acupuncture therapy after the observation period. The primary outcome measure will be the Unified Parkinson's Disease Rating Scale score. The secondary outcome measures will be the scores of the Hoehn-Yahr Rating Scale, Unified Dyskinesia Rating Scale, Non-Motor Symptoms Scale, 39-item Parkinson's Disease Questionnaire, Parkinson Anxiety Scale, Hamilton Anxiety Scale, Hamilton Depression Scale, Zarit burden interview and the level of cortisol and adrenocorticotropic hormone. The evaluation will be executed at baseline, the end of the treatment and a follow-up period. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine (K[2023]014). All patients have to provide written, informed consent. The study will be disseminated through presentations in peer-reviewed international journals and at national and international conferences. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry; ChiCTR2300074675.

An examination of anxiety and its influence on health-related quality of life in Parkinson's disease using the geriatric anxiety scale: a cross-sectional study.

BACKGROUND: Anxiety is one of the most common but often overlooked mood-related nonmotor symptoms in people with Parkinson's disease (PD). To improve the well-being of people with PD, it is important to understand the impact of anxiety in PD, especially its association with depressive and motor symptoms and its impact on health-related quality of life (HRQoL). METHODS: 91 people with PD were assessed between June 2017 and June 2018. Anxiety was measured using the Geriatric Anxiety Scale (GAS) and its cognitive, somatic, and affective subscales. HRQoL was assessed using the Parkinson's Disease Questionnaire 39 (PDQ-39). Moreover, sociodemographic information, depressive symptoms, cognition, motor and nonmotor symptoms were assessed. Descriptive statistics, regression analyses, and path analyses were performed to understand predictors of anxiety and its influence on HRQoL. RESULTS: Of the 91 people with PD, 35 (38.5%) experienced anxiety. Anxiety symptoms in these individuals primarily manifest as somatic sensations. Anxiety, motor, and depressive symptoms are interlinked but contribute individually to HRQoL. Beyond motor symptoms, cognitive and affective aspects of anxiety impact HRQoL. While anxiety and depression overlap, the somatic and cognitive aspects of anxiety play a significant role in determining HRQoL in addition to depressive symptoms. CONCLUSION: Our study used the GAS and its three subscales to shed light on the connections between anxiety, depression, and motor impairment in people with PD. Although anxiety is linked to depression and motor symptoms, it independently affects the HRQoL of people with PD. Thus, it is crucial to adopt a comprehensive diagnostic approach that detects and considers the impact of anxiety on HRQoL in PD.

Effect of levodopa on postural blood pressure changes in Parkinson disease: a randomized crossover study.

PURPOSE: We investigated the effect of levodopa on postural blood pressure changes in individuals with Parkinson disease (PD) with (PD+OH) and without neurogenic OH (PD-OH). METHODS: We performed a prospective randomized crossover study with autonomic testing performed ON and OFF levodopa. The primary outcome was the change in systolic blood pressure (SBP) from supine to 70° tilt at 3 min (ΔSBP-3'). Secondary outcomes included indices of baroreflex function and blood pressure and heart rate during tilt. RESULTS: We enrolled 40 individuals with PD (21 PD+OH, 19 PD-OH), mean age (SD) 73.2 years (7.9), 13 women (32.5%)). There was no difference in age, sex, disease duration, and severity between PD+OH and PD-OH. Mean difference in ΔSBP-3' ON versus OFF levodopa in the whole study population was - 3.20 mmHg [- 7.36 to 0.96] (p = 0.14). Mean difference in ΔSBP-3' was - 2.14 mmHg [- 7.55 to 3.28] (p = 0.45) in PD+OH and - 5.14 mmHg [- 11.63 to 1.35] (p = 0.14) in PD-OH. Mean difference in ΔSBP ON versus OFF levodopa was greater at 7 and 10 min (- 7.52 mmHg [- 11.89 to - 3.15], p = 0.002, and - 7.82 mmHg [- 14.02 to - 1.67], p = 0.02 respectively). Levodopa was associated with lower absolute values of blood pressure in both PD+OH and PD-OH and cardiovascular noradrenergic baroreflex impairment. CONCLUSION: Levodopa decreases blood pressure in both PD with and without autonomic failure, but it does not cause a greater fall in blood pressure from supine to standing at 3 min. Levodopa-induced baroreflex sympathetic noradrenergic impairment may contribute to lower blood pressure. Lower standing blood pressure with levodopa may increase the risks of fall and syncope.

Metformin use is associated with reduced mortality risk in diabetic patients with Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) and type-2 diabetes (T2D) arguably share pathophysiologic mechanisms, resulting in a more severe phenotype and progression and diabetes is currently considered a risk factor of PD. Besides, research suggests antidiabetic therapies as potential disease-modifying strategies. The main aim was to assess the impact of a metformin-inclusive antidiabetic treatment on patient all-cause mortality. METHODS: A nested case-control prospective study including newly diagnosed PD patients reporting the onset of T2D within ±2 years from the onset of PD (n = 159) and matched (1:5; gender, year of PD onset and age at PD onset) non-diabetic cases (n = 795) followed until death or censoring. Patients on a metformin-inclusive treatment regimen were compared to those receiving other oral anti-diabetics (OADs). RESULTS: Among patients with T2D, 123 were treated with a drug regimen containing metformin (alone [65.0%] or in combination with other drugs [35.0%]) and 36 were prescribed other OADs. During a median PD duration of 96 months [IQR, 60-144], 171 patients died. Diabetes was not associated with reduced survival: fully-adjusted HR = 1.19 [95%CI, 0.81-1.76] (P = 0.37). After stratifying for T2D treatment, a metformin-inclusive regimen was not associated with increased risk of death (HR = 1.06 [95%CI, 0.61-1.84]; P = 0.83), while patients receiving other OADs had reduced survival (HR = 1.83 [95%CI, 1.01-3.32]; P = 0.034). CONCLUSIONS: Metformin use was not associated with increased risk of death in diabetic patients with PD reporting concomitant onset of the two diseases. Metformin appears to be a promising disease-modifying therapy given also the preclinical background, low cost and satisfactory safety and tolerability. Further studies are warranted to investigate its impact on disease progression.

Physical activity in Parkinson's disease: examining prescription sources, patterns, and the influence of quality of life and disease severity. / La actividad física en la enfermedad de Parkinson: identificación de los responsables de su prescripción, hábitos e impacto en la calidad de vida, y de la gravedad de la enfermedad.

INTRODUCTION: Limited research has explored the influence of quality of life (QoL) and disease severity on physical activity (PA) in Parkinson's disease (PD) patients, and the sources of PA prescription and advice for this population. This study aims to expand scientific knowledge on these topics. PATIENTS AND METHODS: Two-hundred eleven PD patients were personally interviewed to collect data on PA levels using the International Physical Activity Questionnaire-Short Form and QoL using the Parkinson's Disease Questionnaire-8. An ad hoc questionnaire gathered information on disease severity (Hoehn and Yahr stages), PA behaviors, and PA recommendations. RESULTS: Weak but significant associations were found between PA levels, disease severity (r: -0.218; p = 0.004), and QoL (r: -0.244; p = 0.001). Most participants (85%) received PA counselling, predominantly from neurologists, either at diagnosis (52%) or shortly after (28%). Before PD onset, ~86% engaged in PA, decreasing to 66% post-diagnosis. Approximately 78% reported changes in PA, including reduced frequency (18.4%) and duration (32.8%), with walking as the primary activity. CONCLUSIONS: Disease severity and QoL significantly affect PA levels in PD patients. Diagnosis is associated with decreased PA frequency and duration, and walking is the preferred activity. Neurologists primarily provide PA advice.

TITLE: La actividad física en la enfermedad de Parkinson: identificación de los responsables de su prescripción, hábitos e impacto en la calidad de vida, y de la gravedad de la enfermedad.Introducción. Escasas investigaciones han explorado la influencia de la calidad de vida (CV) y la gravedad de la enfermedad en la actividad física (AF) en pacientes con enfermedad de Parkinson (EP), así como las fuentes de prescripción de AF y consejos para esta población. Este estudio tiene como objetivo ampliar el conocimiento científico sobre estos temas. Pacientes y métodos. Se entrevistó personalmente a 211 pacientes con EP para recopilar datos sobre los niveles de AF con el International Physical Activity Questionnaire-Short Form y la CV con el Parkinson's Disease Questionnaire-8. Un cuestionario ad hoc recopiló información sobre la gravedad de la enfermedad (etapas de Hoehn y Yahr), los comportamientos de AF y las recomendaciones de AF. Resultados. Se encontraron asociaciones débiles, pero significativas, entre los niveles de AF, la gravedad de la enfermedad (r = ­0,218; p = 0,004) y la CV (r = ­0,244; p = 0,001). La mayoría de los participantes (85%) recibió asesoramiento sobre AF, principalmente de neurólogos, ya sea en el momento del diagnóstico (52%) o poco después (28%). Antes del inicio de la EP, ~86% participaba en AF, lo que disminuyó al 66% después del diagnóstico. Aproximadamente el 78% informó sobre cambios en la AF, incluida una reducción en la frecuencia (18,4%) y la duración (32,8%), y la caminata era la actividad principal. Conclusiones. La gravedad de la enfermedad y la CV afectan significativamente a los niveles de AF en pacientes con EP. El diagnóstico se asocia con una disminución en la frecuencia y la duración de la AF, y la caminata es la actividad preferida. Los neurólogos aconsejan principalmente sobre AF a las personas con EP.