Effects of melatonin prolonged-release on both sleep and motor symptoms in Parkinson's disease: a preliminary evidence

background sleep-related symptoms, especially insomnia, are frequently reported by patients with parkinson's disease (PD) and can markedly affect motor symptoms and impair patients' quality of life. melatonin has been shown to improve sleep in PD patients. this pilot study aimed at evaluating the effects of a 3-month treatment with 2 mg melatonin prolonged-release (PR) on sleep and motor disability in PD patients. materials and methods twelve PD patients under stable antiparkinsonian treatment were enrolled in the study. before treatment (T0), motor dysfunction was assessed with unified parkinson's disease rating scale (UPDRS-III) and sleep architecture with polysomnography. subjective sleep quality was also assessed through pittsburgh sleep quality Index (PSQI) and daytime somnolence with epworth sleepiness Scale (ESS). patients then started melatonin PR and all measures were repeated at the end of treatment after 3 months (T1). results sleep latency significantly decreased from T0 to T1, but no other significant differences were found in PSG parameters. melatonin PR treatment significantly reduced the ESS scores from T0 to T1, while the PSQI scores presented a trend of improvement from T0 to T1. motor dysfunction was not improved by melatonin PR, although there was a trend in decreasing UPDRS-III. both clinical global improvement and patient clinical global impression documented an improvement in insomnia symptoms at T1. conclusions these findings suggest that melatonin may improve sleep symptoms in PD patients, although further evidence is needed in larger controlled studies to confirm these results and explore the possible direct and indirect influence of sleep improvement on motor dysfunction

Cerebellar white matter disruption in Alzheimer’s Disease patients: a Diffusion Tensor Imaging study

The cognitive role of the cerebellum has recently gained much attention, and its pivotal role in Alzheimer’s disease (AD) has now been widely recognized. Diffusion tensor imaging (DTI) has been used to evaluate the disruption of the microstructural milieu in AD, and though several white matter (WM) tracts such as corpus callosum, inferior and superior longitudinal fasciculus, cingulum, fornix, and uncinate fasciculus have been evaluated in AD, data on cerebellar WM tracts are currently lacking. We performed a tractography-based DTI reconstruction of the middle cerebellar peduncle (MCP), and the left and right superior cerebellar peduncles separately (SCPL and SCPR) and addressed the differences in fractional anisotropy (FA), axial diffusivity (Dax), radial diffusivity (RD), and mean diffusivity (MD) in the three tracts between 50 patients with AD and 25 healthy subjects. We found that AD patients showed a lower FA and a higher RD compared to healthy subjects in MCP, SCPL, and SCPR. Moreover, a higher MD was found in SCPR and SCPL and a higher Dax in SCPL. This result is important as it challenges the traditional view that WM bundles in the cerebellum are unaffected in AD and might identify new targets for therapeutic interventions

Assessment of Psychometric Characteristics of Parkinson’s Disease Sleep Scale 2 and Analysis of a Cut-Off Score for Detecting Insomnia in Italian Patients with Parkinson’s Disease: A Validation Study

introduction: sleep disorders are frequent non-motor symptoms affecting patients with parkinson's disease (PD). Insomnia represents the most common sleep disorder. parkinson's disease Sleep Scale 2 (PDSS-2) is a specific tool to investigate sleep problems in PD. the general sleep disturbances scale (GSDS) was a general scale validated for the Italian population. our goal was to assess the psychometric characteristics of PDSS-2 and the GSDS in this population, calculating a cut-off score for insomnia symptoms by using subitems of PDSS-2. methods: patients admitted at the PD unit of the hospital of rome tor vergata outpatient clinic and those afferent to PD associations were asked to complete PDSS-2 and GSDS to be correlated to identify a cut-off for insomnia symptoms. Items 1,2,3,8,13 of PDSS-2 were used to detect insomnia. an ROC curve to assess a cut-off score for insomnia was determined. a cross-cultural analysis of PD population characteristics was performed. results: In total, 350 PD patients were recruited. cronbach's alpha was high for the total score (0.828 for PDSS-2 and 0.832 for GSDS). a cross-cultural analysis did not show any significant p-value. the ROC curve yielded an AUC of 0.79 (CI: 0.75-0.84). the cut-off value for insomnia disorder based on items 1,2,3,8,13 of PDSS-2 was >10, demonstrating a sensitivity of 76% and a specificity of 69% in determining the presence of subjective insomnia symptoms in PD. discussion: PDSS-2 is demonstrated to be a valid, specific tool to address sleep disturbances in PD patients. a cut-off score of 10 for items 1,2,3,8,13 was identified for detecting insomnia symptoms in PD patients

Differences in CSF Biomarkers Profile of Patients with Parkinson's Disease Treated with MAO-B Inhibitors in Add-On

Monoamine oxidase type B inhibitors (iMAO-Bs) are a class of largely-used antiparkinsonian agents that, based on experimental evidence, are supposed to exert different degrees of neuroprotection in Parkinson's disease (PD). However, clinical proofs on this regard are very scarce. Since cerebrospinal fluid (CSF) reflects pathological changes occurring at brain level, we examined the neurodegeneration-related CSF biomarkers profile of PD patients under chronic treatment with different iMAO-Bs to identify biochemical signatures suggestive for differential neurobiological effects.Thirty-five PD patients under chronic treatment with different iMAO-Bs in add-on to levodopa were enrolled and grouped in rasagiline (n = 13), selegiline (n = 9), safinamide (n = 13). Respective standard clinical scores for motor and non-motor disturbances, together with CSF biomarkers of neurodegeneration levels (amyloid- β -42, amyloid- β -40, total and 181-phosphorylated tau, and lactate) were collected and compared among the three iMAO-B groups.No significant clinical differences emerged among the iMAO-B groups. CSF levels of tau proteins and lactate were instead different, resulting higher in patients under selegiline than in those under rasagiline and safinamide.Although preliminary and limited, this study indicates that patients under different iMAO-Bs may present distinct profiles of CSF neurodegeneration-related biomarkers, probably because of the differential neurobiological effects of the drugs. Larger studies are now needed to confirm and extend these initial observations

In vivo mapping of brainstem nuclei functional connectivity disruption in Alzheimer's disease

We assessed here functional connectivity changes in the locus coeruleus (LC) and ventral tegmental area (VTA) of patients with Alzheimer's disease (AD). We recruited 169 patients with either AD or amnestic mild cognitive impairment due to AD and 37 elderly controls who underwent cognitive and neuropsychiatric assessments and resting-state functional magnetic resonance imaging at 3T. Connectivity was assessed between LC and VTA and the rest of the brain. In amnestic mild cognitive impairment patients, VTA disconnection was predominant with parietal regions, while in AD patients, it involved the posterior nodes of the default-mode network. We also looked at the association between neuropsychiatric symptoms (assessed by the neuropsychiatric inventory) and VTA connectivity. Symptoms such as agitation, irritability, and disinhibition were associated with VTA connectivity with the parahippocampal gyrus and cerebellar vermis, while sleep and eating disorders were associated with VTA connectivity to the striatum and the insular cortex. This suggests a contribution of VTA degeneration to AD pathophysiology and to the occurrence of neuropsychiatric symptoms. We did not find evidence of LC disconnection, but this could be explained by the size of this nucleus, which makes it difficult to isolate. These results are consistent with animal findings and have potential implications for AD prognosis and therapies

Non-motor symptoms burden in motor-fluctuating patients with Parkinson's disease may be alleviated by safinamide: the VALE-SAFI study

parkinson's disease (PD) is characterized by motor symptoms often experienced in concomitance with non-motor symptoms (NMS), such as depression, apathy, pain, sleep disorders, and urinary dysfunction. the present study aimed to explore the effect of safinamide treatment on NMS and quality of life in motor-fluctuating PD patients. VALE-SAFI is an observational single-centre study performed in fluctuating PD patients starting safinamide treatment and followed for 6 months. the effects of safinamide on NMS, sleep, fatigue, depression and pain were assessed through validated sales. changes in the scales from baseline to the 6-month follow-up visit were analysed. 60 PD patients (66.67% males) were enrolled at baseline, and 45 patients completed the 6-month follow-up. PD patients improved motor symptoms at follow-up, with the significant reduction of motor fluctuations. the global score of the NMS Scale significantly decreased between baseline and the follow-up. regarding pain domains, patients reported a significant improvement in discolouration and oedema/swelling. further, a significant improvement was observed from baseline to follow-up in sleep quality measured through the pittsburgh sleep quality Index, while no changes were documented in daytime sleepiness. no differences were found in depression and fatigue between baseline and follow-up. finally, the patient's perception of the impact of PD on functioning and well-being decreased from baseline to follow-up. the present findings confirmed the beneficial effect of safinamide on both motor and non-motor symptoms, also improving the quality of life of PD patients. furthermore, these data support the positive effects of safinamide on pain and mood, as well as on sleep quality and continuity

From traumatic childhood to cocaine abuse: the critical function of the immune system

Background: Experiencing traumatic childhood is a risk factor for developing substance use disorder (SUD), but the mechanisms that underlie this relationship have not been determined. Adverse childhood experiences affect the immune system and the immune system mediates the effects of psychostimulants. However, whether this system is involved in the etiology of SUD in individuals who have experience early life stress is unknown. Methods:In this study, we performed a series of ex vivo and in vivo experiments in mice and humans to define the function of the immune system in the early-life stress-induced susceptibility to the neurobehavioral effects of cocaine. Results: We provide evidence that exposure to social-stress (S-S) at an early age permanently sensitizes the peripheral (splenocytes) and brain (microglia) immune responses to cocaine in mice. In the brain, microglial activation in the ventral tegmental area (VTA) of S-S mice was associated with functional alterations in dopaminergic neurotransmission, as measured by whole-cell voltage clamp recordings in dopamine (DA) neurons. Notably, preventing immune activation during the S-S exposure reverted the effects of DA in the VTA and the cocaine-induced behavioral phenotype to control levels. In humans, cocaine modulated Toll-like receptor 4-mediated innate immunity, an effect that was enhanced in cocaine addicts who had experienced a difficult childhood. Conclusions Collectively, our findings demonstrate that sensitization to cocaine in early-life-stressed individuals involves brain and peripheral immune responses and that this mechanism is shared between mice and humans