Targeting the adenosinergic system in restless legs syndrome: A pilot, "proof-of-concept" placebo-controlled TMS-based protocol.

Restless Legs Syndrome (RLS) is a common sleep disorder characterized by an urge to move the legs that is responsive to movement (particularly during rest), periodic leg movements during sleep, and hyperarousal. Recent evidence suggests that the involvement of the adenosine system may establish a connection between dopamine and glutamate dysfunction in RLS. Transcranial magnetic stimulation (TMS) is a non-invasive electrophysiological technique widely applied to explore brain electrophysiology and neurochemistry under different experimental conditions. In this pilot study protocol, we aim to investigate the effects of dipyridamole (a well-known enhancer of adenosinergic transmission) and caffeine (an adenosine receptor antagonist) on measures of cortical excitation and inhibition in response to TMS in patients with primary RLS. Initially, we will assess cortical excitability using both single- and paired-pulse TMS in patients with RLS. Then, based on the measures obtained, we will explore the effects of dipyridamole and caffeine, in comparison to placebo, on various TMS parameters related to cortical excitation and inhibition. Finally, we will evaluate the psycho-cognitive performance of RLS patients to screen them for cognitive impairment and/or mood-behavioral dysfunction, thus aiming to correlate psycho-cognitive findings with TMS data. Overall, this study protocol will be the first to shed lights on the neurophysiological mechanisms of RLS involving the modulation of the adenosine system, thus potentially providing a foundation for innovative "pharmaco-TMS"-based treatments. The distinctive TMS profile observed in RLS holds indeed the potential utility for both diagnosis and treatment, as well as for patient monitoring. As such, it can be considered a target for both novel pharmacological (i.e., drug) and non-pharmacological (e.g., neuromodulatory), "TMS-guided", interventions.

Predominant cardiac sympathetic modulation during wake and sleep in patients with Rett syndrome.

BACKGROUND: Rett syndrome (RTT) is a rare neurological disorder primarily associated with mutations in the methyl-CpG-binding protein 2 (MECP2) gene. The syndrome is characterized by cognitive, social, and physical impairments, as well as sleep disorders and epilepsy. Notably, dysfunction of the autonomic nervous system is a key feature of the syndrome. Although Heart Rate Variability (HRV) has been used to investigate autonomic nervous system dysfunction in RTT during wakefulness, there is still a significant lack of information regarding the same during sleep. Therefore, our aim was to investigate cardiovascular autonomic modulation during sleep in subjects with RTT compared to an age-matched healthy control group (HC). METHOD: A complete overnight polysomnographic (PSG) recording was obtained from 11 patients with Rett syndrome (all females, 10 ± 4 years old) and 11 HC (all females, 11 ± 4 years old; p = 0.48). Electrocardiogram and breathing data were extracted from PSG and divided into wake, non-REM, and REM sleep stages. Cardiac autonomic control was assessed using symbolic non-linear heart rate variability analysis. The symbolic analysis identified three patterns: 0 V% (sympathetic), 2UV%, and 2LV% (vagal). RESULTS: The 0 V% was higher in the RTT group than in the HC group during wake, non-REM, and REM stages (p < 0.01), while the 2LV and 2UV% were lower during wake and sleep stages (p < 0.01). However, the 0 V% increased similarly from the wake to the REM stage in both RTT and HC groups. CONCLUSIONS: Therefore, the sympatho-vagal balance shifted towards sympathetic predominance and vagal withdrawal during wake and sleep in RTT, although cardiac autonomic dynamics were preserved during sleep.

Low TGF-ß1 plasma levels are associated with cognitive decline in Down syndrome.

Almost all individuals with Down's syndrome (DS) show the characteristic neuropathological features of Alzheimer's disease (AD) by the age of 40, yet not every individual with DS experiences symptoms of AD later in life. Similar to neurotypical developing subjects, AD in people with DS lasts for a long preclinical phase in which biomarkers follow a predictable order of changes. Hence, a prolonged asymptomatic period precedes the onset of dementia, underscoring the importance of identifying new biomarkers for the early detection and monitoring of cognitive decline in individuals with DS. Blood-based biomarkers may offer an alternative non-invasive strategy for the detection of peripheral biological alterations paralleling nervous system pathology in an early phase of the AD continuum. In the last few years, a strong neurobiological link has been demonstrated between the deficit of transforming growth factor-ß1 (TGF-ß1) levels, an anti-inflammatory cytokine endowed with neuroprotective activity, and early pro-inflammatory processes in the AD brain. In this clinical prospective observational study, we found significant lower plasma TGF-ß1 concentrations at the first neuropsychological evaluation (baseline = T0) both in young adult DS individuals (19-35 years) and older DS subjects without AD (35-60 years) compared to age- and sex-matched healthy controls. Interestingly, we found that the lower TGF-ß1 plasma concentrations at T0 were strongly correlated with the following cognitive decline at 12 months. In addition, in young individuals with DS, we found, for the first time, a negative correlation between low TGF-ß1 concentrations and high TNF-α plasma concentrations, a pro-inflammatory cytokine that is known to be associated with cognitive impairment in DS individuals with AD. Finally, adopting an ex vivo approach, we found that TGF-ß1 concentrations were reduced in parallel both in the plasma and in the peripheral blood mononuclear cells (PBMCs) of DS subjects, and interestingly, therapeutic concentrations of fluoxetine (FLX) applied to cultured PBMCs (1 µM for 24 h) were able to rescue TGF-ß1 concentrations in the culture media from DS PBMCs, suggesting that FLX, a selective serotonin reuptake inhibitor (SSRI) endowed with neuroprotective activity, might rescue TGF-ß1 concentrations in DS subjects at higher risk to develop cognitive decline.

Unveiling the pathophysiology of restless legs syndrome through transcriptome analysis.

The aim of this study was to analyze signaling pathways associated with differentially expressed messenger RNAs in people with restless legs syndrome (RLS). Seventeen RLS patients and 18 controls were enrolled. Coding RNA expression profiling of 12,857 gene transcripts by next-generation sequencing was performed. Enrichment analysis by pathfindR tool was carried-out, with p-adjusted ≤0.001 and fold-change ≥2.5. Nine main different network groups were significantly dysregulated in RLS: infections, inflammation, immunology, neurodegeneration, cancer, neurotransmission and biological, blood and metabolic mechanisms. Genetic predisposition plays a key role in RLS and evidence indicates its inflammatory nature; the high involvement of mainly neurotropic viruses and the TORCH complex might trigger inflammatory/immune reactions in genetically predisposed subjects and activate a series of biological pathways-especially IL-17, receptor potential channels, nuclear factor kappa-light-chain-enhancer of activated B cells, NOD-like receptor, mitogen-activated protein kinase, p53, mitophagy, and ferroptosis-involved in neurotransmitter mechanisms, synaptic plasticity, axon guidance, neurodegeneration, carcinogenesis, and metabolism.

A survey-based approach on restless legs syndrome: practices and perspectives among Italian neurologists.

INTRODUCTION: Restless Legs Syndrome (RLS) is a widely prevalent and complex neurological disorder. Despite notable advancements in managing RLS, the disorder continues to face challenges related to its recognition and management. OBJECTIVE: This study seeks to gain comprehensive insights into the knowledge and clinical practices among Italian neurologists regarding RLS diagnosis, management, and treatment, comparing approaches among general neurologists, movement disorder specialists, and sleep experts. METHODS: Members of the Italian Society of Neurology, the Italian Society of Parkinson and Movement Disorders, and the Italian Association of Sleep Medicine were invited to participate in a 19-question online survey. RESULTS: Among the 343 surveyed neurologists, 60% categorized RLS as a "sleep-related movement disorder." Forty% indicated managing 5-15 RLS patients annually, with sleep specialists handling the highest patient volume. Of note, only 34% adhered strictly to all five essential diagnostic criteria. The majority (69%) favored low-dosage dopamine agonists as their first-line treatment, with movement disorder specialists predominantly endorsing this approach, while sleep experts preferred iron supplementation. Regular screening for iron levels was widespread (91%), with supplementation typically guided by serum iron alterations. In cases of ineffective initial treatments, escalating dopamine agonist dosage was the preferred strategy (40%). CONCLUSIONS: These findings underscore a lack of a clear conceptualization of RLS, with a widespread misconception of the disorder as solely a movement disorder significantly influencing treatment approaches. Disparities in RLS understanding across neurology subspecialties underscore the necessity for improved diagnostic accuracy, targeted educational initiatives, and management guidelines to ensure consistent and effective RLS management.

Periodic limb movement disorder in children: A systematic review.

This systematic review evaluates the scientific literature on pediatric periodic limb movement disorder (PLMD), adhering to PRISMA guidelines and utilizing PICOS criteria. The search across PubMed, EMBASE, and Scopus yielded 331 articles, with 17 meeting inclusion criteria. Diagnostic criteria evolved, with polysomnography and PLMS index ≥5 required since 2003. Also, PLMD diagnosis mandates clinical consequences like insomnia, hypersomnia, and fatigue, excluding comorbidities causing sleep disruption. Prevalence in children is low (0.3%), emphasizing the need for meticulous investigation. Comorbidities, particularly the bidirectional relationship with ADHD, were explored. Challenges in diagnosis and understanding arise from overlapping conditions such as sleep disordered breathing, psychotropic medication, and criteria non-adherence. Despite generally good study quality, weaknesses include sample size justification and biases. The periodic leg movement index shows high sensitivity but low specificity, underscoring strict diagnostic criteria adherence. Diverse metrics for symptoms necessitate standardized approaches. Family history of RLS in children with PLMD suggests unexplored aspects. Treatment, mainly iron supplementation, lacks standardized assessment metrics. The review emphasizes diagnostic and treatment challenges, recommending unbiased studies with precise techniques. Comprehensive research, quantifying PLMS and objectively assessing sleep parameters, is crucial for advancing understanding in pediatric PLMD. PROSPERO REGISTRATION NUMBER: CRD42021251406.

Age related disparities in sleep apnea diagnosis using a wearable device: Implications of 4% vs. 3% hypopnea scoring criteria.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) diagnosis relies on the Apnea-Hypopnea Index (AHI), with discrepancies arising from the 3% and 4% desaturation criteria. This study investigates age-related variations in OSA severity classification, utilizing data from 1201 adult patients undergoing Home Sleep Apnea Testing (HSAT) with SleepImage Ring@. METHODS: The study employs Bland-Altman analysis to compare AHI values obtained with the 3% and 4% desaturation criteria. Age-stratified analysis explores discrepancies across different age groups. RESULTS: The analysis reveals a systematic bias favoring the 3% criterion, impacting the quantification of apnea events. Age-specific patterns demonstrate diminishing agreement between criteria with increasing age. CONCLUSION: This comprehensive study underscores the importance of standardized criteria in OSA diagnosis. The findings emphasize age-specific considerations and ethical concerns, providing crucial insights for optimizing patient care and advancing sleep medicine practices.

The association between posterior resting-state EEG alpha rhythms and functional MRI connectivity in older adults with subjective memory complaint.

Resting-state eyes-closed electroencephalographic (rsEEG) alpha rhythms are dominant in posterior cortical areas in healthy adults and are abnormal in subjective memory complaint (SMC) persons with Alzheimer's disease amyloidosis. This exploratory study in 161 SMC participants tested the relationships between those rhythms and seed-based resting-state functional magnetic resonance imaging (rs-fMRI) connectivity between thalamus and visual cortical networks as a function of brain amyloid burden, revealed by positron emission tomography and cognitive reserve, measured by educational attainment. The SMC participants were divided into 4 groups according to 2 factors: Education (Edu+ and Edu-) and Amyloid burden (Amy+ and Amy-). There was a statistical interaction (p < 0.05) between the two factors, and the subgroup analysis using estimated marginal means showed a positive association between the mentioned rs-fMRI connectivity and the posterior rsEEG alpha rhythms in the SMC participants with low brain amyloidosis and high CR (Amy-/Edu+). These results suggest that in SMC persons, early Alzheimer's disease amyloidosis may contrast the beneficial effects of cognitive reserve on neurophysiological oscillatory mechanisms at alpha frequencies and connectivity between the thalamus and visual cortical networks.

Resting-state EEG rhythms are abnormal in post COVID-19 patients with brain fog without cognitive and affective disorders.

OBJECTIVES: Several persons experiencing post-covid-19 (post-COVID) with "brain fog" (e.g., fatigue, cognitive and psychiatric disorders, etc.) show abnormal resting-state electroencephalographic (rsEEG) rhythms reflecting a vigilance dysfunction. Here, we tested the hypothesis that in those post-COVID persons, abnormal rsEEG rhythms may occur even when cognitive and psychiatric disorders are absent. METHODS: The experiments were performed on post-COVID participants about one year after hospitalization for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Inclusion criteria included a "brain fog" claim, no pre-infection, and actual organic chronic disease. Matched controls (no COVID) were also enrolled. All participants underwent clinical/neuropsychological assessment (including fatigue assessment) and rsEEG recordings. The eLORETA freeware estimated regional rsEEG cortical sources at individual delta (<4 Hz), theta (4-7 Hz), and alpha (8-13 Hz) bands. Beta (14-30 Hz) and gamma (30-40 Hz) bands were pre-fixed. RESULTS: More than 90% of all post-COVID participants showed no cognitive or psychiatric disorders, and 75% showed ≥ 2 fatigue symptoms. The post-COVID group globally presented lower posterior rsEEG alpha source activities than the Control group. This effect was more significant in the long COVID-19 patients with ≥ 2 fatigue symptoms. CONCLUSIONS: In post-COVID patients with no chronic diseases and cognitive/psychiatric disorders, "brain fog" can be associated with abnormal posterior rsEEG alpha rhythms and subjective fatigue. SIGNIFICANCE: These abnormalities may be related to vigilance and allostatic dysfunctions.

Resting state electroencephalographic alpha rhythms are sensitive to Alzheimer's disease mild cognitive impairment progression at a 6-month follow-up.

Are posterior resting-state electroencephalographic (rsEEG) alpha rhythms sensitive to the Alzheimer's disease mild cognitive impairment (ADMCI) progression at a 6-month follow-up? Clinical, cerebrospinal, neuroimaging, and rsEEG datasets in 52 ADMCI and 60 Healthy old seniors (equivalent groups for demographic features) were available from an international archive (www.pdwaves.eu). The ADMCI patients were arbitrarily divided into two groups: REACTIVE and UNREACTIVE, based on the reduction (reactivity) in the posterior rsEEG alpha eLORETA source activities from the eyes-closed to eyes-open condition at ≥ -10% and -10%, respectively. 75% of the ADMCI patients were REACTIVE. Compared to the UNREACTIVE group, the REACTIVE group showed (1) less abnormal posterior rsEEG source activity during the eyes-closed condition and (2) a decrease in that activity at the 6-month follow-up. These effects could not be explained by neuroimaging and neuropsychological biomarkers of AD. Such a biomarker might reflect abnormalities in cortical arousal in quiet wakefulness to be used for clinical studies in ADMCI patients using 6-month follow-ups.

Polysomnographic features associated with clonazepam and melatonin treatment in isolated REM sleep behavior disorder: Time for new therapeutic approaches?

AIMS: Although clonazepam (CLO) and melatonin (MLT) are the most frequently used treatments for REM sleep behavior disorder, the polysomnographic features associated with their use are little known. The aim of this study was to evaluate polysomnographic and clinical parameters of patients with idiopathic/isolated REM sleep behavior disorder (iRBD) treated chronically with CLO, sustained-release MLT, alone or in combination, and in a group of drug-free iRBD patients. METHODS: A total of 96 patients were enrolled: 43 drug-free, 21 with CLO (0.5-2 mg), 20 with sustained-release MLT (1-4 mg), and 12 taking a combination of them (same doses). Clinical variables and polysomnography were collected. RESULTS: Although clinical improvement was reported in all groups, MLT impacted sleep architecture more than the other treatments, with significant and large increase in N3 stage, moderate reduction in N2 and REM sleep, and moderate increase in REM latency. CLO moderately increased the percentage of both REM sleep and especially N2, while reducing N1 and wakefulness. Patients treated with both CLO and MLT did not show major changes in sleep architecture. CONCLUSION: These results suggest that the administration of MLT or CLO impacts (positively) on sleep parameters of iRBD patients. However, there is a need to better stratify patients, in order to treat them in a targeted manner, depending on the patient's individual sleep architecture and expected differential effects of these agents.

Biomarkers of neurodegeneration in isolated and antidepressant-related rapid eye movement sleep behavior disorder.

BACKGROUND AND PURPOSE: This study compared the features of isolated rapid eye movement (REM) sleep behavior disorder (iRBD) and antidepressant-related REM sleep behaviour disorder (RBD) with the aim of highlighting markers that might distinguish the two entities. METHODS: The observational cohort study included RBD patients with and without antidepressant use (antiD+ and antiD- patients, respectively), without cognitive impairment and parkinsonism. Clinical features of RBD, subtle motor and non-motor symptoms of parkinsonism, sleep architecture, REM atonia index, dopamine transporter-single photon emission computed tomography (DAT-SPECT) and skin biopsies for the intraneuronal alpha-synuclein (α-syn), were evaluated in the baseline work-up. RESULTS: Thirty-nine patients, 10 antiD+ and 29 antiD-, were included. AntiD+ patients (more frequently female) reported more psychiatric symptoms, less violent dream enactment, and less frequent hyposmia. Dermal α-syn was detected in 93.1% of antiD- versus 30% of antiD+ patients (p = 0.00024). No differences appeared in other motor and non-motor symptoms, Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III score, DAT-SPECT, or polysomnographic features. CONCLUSIONS: Patients with antidepressant-related RBD have clinical and neuropathological features suggesting a lower risk of evolution than those with iRBD.

Sleep and follow-up characteristics of Hispanic patients: Insights from a comparative analysis with White patients in polysomnographic split-night studies.

BACKGROUND: Limited attention has been given to exploring the efficacy of titration in split-night polysomnography (PSG) and the factors influencing adherence to continuous positive airway pressure (CPAP) therapy. This study aims to evaluate the severity of OSA and PSG parameters in HP compared to WP. METHODS: Split-night PSG studies conducted on adults. Participants were categorized based on self-reported ethnicity as either HP or WP. RESULTS: The study enrolled 50 WP (15 women, 35 men, mean age 60.5 ± 13.60 years, mean BMI 34.2 ± 7.48) and 45 HP (24 women, 21 men, mean age 54.9 ± 13.06 years, mean BMI 37.3 ± 7.88). HP exhibited a mean apnea-hypopnea index (AHI) of 51.1 ± 33.67, saturation nadir of 77.8 ± 10.19, and time spent with saturation <90% of 21.0 ± 26.93 min. In WP, the mean AHI was 39.2 ± 24.49, saturation nadir 81.6 ± 9.04, and time spent <90% was 10.4 ± 17.17 min. All observed differences were statistically significant (p < 0.05). Auto CPAP was prescribed to all patients, with adherence at 3-4 months being 75% ± 30 for HP, with a usage of 5.5 ± 2.2 h, and a residual AHI of 3 ± 3.5. In WP, adherence was 79% ± 30, usage was 5.9 ± 2.1 h, and residual AHI was 3.6 ± 6.2. None of these differences reached statistical significance. Among HP, 37% missed follow-up appointments compared to 12% of WP. More HP used full-face masks, while more WP preferred nasal masks. CONCLUSIONS: HP exhibited significantly worse OSA parameters during the diagnostic phase of PSG compared to WP. HP had a significantly higher no-show percentage than WP. CPAP adherence and residual AHI were not statistically different, but more HP missed follow-up appointments than WP.

Changes in time structure of periodic leg movements during sleep in restless legs syndrome: Effects of sex and age.

BACKGROUND: The objective of this study was to check the hypothesis that in women with restless legs syndrome (RLS) different changes occur in periodic leg movements during sleep (PLMS) during the post-menopausal period (using >50 years as a proxy) than in men of the same age. METHODS: We recruited 36 untreated patients aged 18-50 years (19 men, median age 40 years, and 17 women, median age 37 years) while the remaining 67 were >50 years old (24 men, median age 66.6 years, and 43 women, median age 60.0 years). Leg movement activity during sleep was analyzed by means of an approach utilizing indexes especially suitable to assess leg movement periodicity. RESULTS: No significant difference was seen between men in the two age groups; conversely, in women, a clear and significant increase in Periodicity Index was observed in the older group, along with a decrease in isolated leg movements. In women, a clear age-related enhancement of PLMS was found in the intermovement interval graphs, especially in the 16-22 s range, which was more evident than that observed in men. The results remained unchanged also when they were replicated by selecting only subjects aged 18-45 years vs. those aged >55 years. CONCLUSIONS: Our findings indicate that assessing PLMS in women after menopause is clinically relevant because they are probably connected with the hormonal fluctuations of this period of life. Translationally, identifying and addressing PLMS in post-menopausal women is crucial for optimizing their sleep health and addressing potential health risks associated with sleep disturbances.

A narrative review on insomnia and hypersomnolence within Major Depressive Disorder and bipolar disorder: A proposal for a novel psychometric protocol.

Sleep disorders have become increasingly prevalent, with many adults worldwide reporting sleep dissatisfaction. Major Depressive Disorder (MDD) and Bipolar Disorder (BD) are common conditions associated with disrupted sleep patterns such as insomnia and hypersomnolence. These sleep disorders significantly affect the progression, severity, treatment, and outcome of unipolar and bipolar depression. While there is evidence of a connection between sleep disorders and depression, it remains unclear if sleep features differ between MDD and BD. In light of this, this narrative review aims to: (1) summarize findings on common sleep disorders like insomnia and hypersomnolence, strongly linked to MDD and BD; (2) propose a novel psychometric approach to assess sleep in individuals with depressive disorders. Despite insomnia seems to be more influent in unipolar depression, while hypersomnolence in bipolar one, there is no common agreement. So, it is essential adopting a comprehensive psychometric protocol for try to fill this gap. Understanding the relationship between sleep and MDD and BD disorders are crucial for effective management and better quality of life for those affected.

The Parasomnias.

Parasomnias usually present in childhood and resolve spontaneously. The diagnosis of non-rapid eye movement-related parasomnias is mainly based on clinical descriptors and can be challenging. Rapid eye movement-related parasomnias may index an underlying psychiatric disorder. Even if benign, parasomnias can affect quality of life. Pediatricians and child psychiatrists should be familiarized with these sleep disorders and suggest adequate sleep hygiene, avoidance of sleep deprivation, and regular bedtimes even on weekends as the first step in management of these disorders. Clinicians should pursue the opportunity for tailoring treatments and consider referral to a sleep expert when indicated.

Restless Legs Syndrome in Children and Adolescents.

Children with psychiatric comorbidities frequently are referred for evaluation of sleep complaints. Common sleep symptoms can include difficulty falling asleep, frequent nocturnal awakening, restless sleep, and symptoms of restless legs syndrome (RLS). The understanding of the sleep condition in relation to the psychiatric comorbidity often is a challenge to the physician and often sleep disorders remain undiagnosed, untreated, or undertreated. Restless legs syndrome has been associated with psychiatric comorbidities and with certain medications, such as antidepressants, antihistamines, and antipsychotics. This article reviews the presentation of RLS and restless sleep, the association with psychiatric comorbidities, and treatment options.

A comprehensive overview of post-stroke depression treatment options.

Nearly one-third of all stroke patients develop depression at any time after a stroke, and its presence is associated with unfavorable outcomes. This narrative review aims to provide a synopsis of possible pharmacological and non-pharmacological treatment modalities for post-stroke depression (PSD). Several studies have demonstrated the efficacy and safety of selective serotonin reuptake inhibitors in treating the symptoms of this clinical condition. The treatment of PSD has been recently enhanced by innovative approaches, such as cognitive-behavioral therapy, virtual reality, telehealth, repetitive transcranial magnetic stimulation, and non-conventional therapies, which might improve depression treatment in stroke survivors. Future high-quality randomized controlled trials are necessary to confirm this hypothesis.

Gene Expression Profiling of Post Mortem Midbrain of Parkinson's Disease Patients and Healthy Controls.

Parkinson's disease (PD) stands as the most prevalent degenerative movement disorder, marked by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. In this study, we conducted a transcriptome analysis utilizing post mortem mRNA extracted from the substantia nigra of both PD patients and healthy control (CTRL) individuals. Specifically, we acquired eight samples from individuals with PD and six samples from CTRL individuals, with no discernible pathology detected in the latter group. RNA sequencing was conducted using the TapeStation 4200 system from Agilent Technologies. A total of 16,148 transcripts were identified, with 92 mRNAs displaying differential expression between the PD and control groups. Specifically, 33 mRNAs were significantly up-regulated, while 59 mRNAs were down-regulated in PD compared to the controls. The identification of statistically significant signaling pathways, with an adjusted p-value threshold of 0.05, unveiled noteworthy insights. Specifically, the enriched categories included cardiac muscle contraction (involving genes such as ATPase Na+/K+ transporting subunit beta 2 (ATP1B2), solute carrier family 8 member A1 (SLC8A1), and cytochrome c oxidase subunit II (COX2)), GABAergic synapse (involving GABA type A receptor-associated protein-like 1 (GABARAPL1), G protein subunit beta 5 (GNB5), and solute carrier family 38 member 2 (SLC38A2), autophagy (involving GABARAPL1 and tumor protein p53-inducible nuclear protein 2 (TP53INP2)), and Fc gamma receptor (FcγR) mediated phagocytosis (involving amphiphysin (AMPH)). These findings uncover new pathophysiological dimensions underlying PD, implicating genes associated with heart muscle contraction. This knowledge enhances diagnostic accuracy and contributes to the advancement of targeted therapies.

Mediterranean Diet and Sleep Features: A Systematic Review of Current Evidence.

The prevalence of sleep disorders, characterized by issues with quality, timing, and sleep duration is increasing globally. Among modifiable risk factors, diet quality has been suggested to influence sleep features. The Mediterranean diet is considered a landmark dietary pattern in terms of quality and effects on human health. However, dietary habits characterized by this cultural heritage should also be considered in the context of overall lifestyle behaviors, including sleep habits. This study aimed to systematically revise the literature relating to adherence to the Mediterranean diet and sleep features in observational studies. The systematic review comprised 23 reports describing the relation between adherence to the Mediterranean diet and different sleep features, including sleep quality, sleep duration, daytime sleepiness, and insomnia symptoms. The majority of the included studies were conducted in the Mediterranean basin and reported a significant association between a higher adherence to the Mediterranean diet and a lower likelihood of having poor sleep quality, inadequate sleep duration, excessive daytime sleepiness or symptoms of insomnia. Interestingly, additional studies conducted outside the Mediterranean basin showed a relationship between the adoption of a Mediterranean-type diet and sleep quality, suggesting that biological mechanisms sustaining such an association may exist. In conclusion, current evidence suggests a relationship between adhering to the Mediterranean diet and overall sleep quality and different sleep parameters. The plausible bidirectional association should be further investigated to understand whether the promotion of a healthy diet could be used as a tool to improve sleep quality.