Derivation and Validation of a Phenoconversion-Related Pattern in Idiopathic Rapid Eye Movement Behavior Disorder.

BACKGROUND: Idiopathic rapid eye movement sleep behavior disorder (iRBD) represents the prodromal stage of α-synucleinopathies. Reliable biomarkers are needed to predict phenoconversion. OBJECTIVE: The aim was to derive and validate a brain glucose metabolism pattern related to phenoconversion in iRBD (iRBDconvRP) using spatial covariance analysis (Scaled Subprofile Model and Principal Component Analysis [SSM-PCA]). METHODS: Seventy-six consecutive iRBD patients (70 ± 6 years, 15 women) were enrolled in two centers and prospectively evaluated to assess phenoconversion (30 converters, 73 ± 6 years, 14 Parkinson's disease and 16 dementia with Lewy bodies, follow-up time: 21 ± 14 months; 46 nonconverters, 69 ± 6 years, follow-up time: 33 ± 19 months). All patients underwent [18 F]FDG-PET (18 F-fluorodeoxyglucose positron emitting tomography) to investigate brain glucose metabolism at baseline. SSM-PCA was applied to obtain the iRBDconvRP; nonconverter patients were considered as the reference group. Survival analysis and Cox regression were applied to explore prediction power. RESULTS: First, we derived and validated two distinct center-specific iRBDconvRP that were comparable and significantly able to predict phenoconversion. Then, SSM-PCA was applied to the whole set, identifying the iRBDconvRP. The iRBDconvRP included positive voxel weights in cerebellum; brainstem; anterior cingulate cortex; lentiform nucleus; and middle, mesial temporal, and postcentral areas. Negative voxel weights were found in posterior cingulate, precuneus, middle frontal gyrus, and parietal areas. Receiver operating characteristic analysis showed an area under the curve of 0.85 (sensitivity: 87%, specificity: 72%), discriminating converters from nonconverters. The iRBDconvRP significantly predicted phenoconversion (hazard ratio: 7.42, 95% confidence interval: 2.6-21.4). CONCLUSIONS: We derived and validated an iRBDconvRP to efficiently discriminate converter from nonconverter iRBD patients. [18 F]FDG-PET pattern analysis has potential as a phenoconversion biomarker in iRBD patients. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The effect of lacosamide monotherapy on sleep architecture in patients with epilepsy: a preliminary evidence.

Lacosamide (LCM) is a third-generation antiseizure medication (ASM), and its effect on sleep architecture was supported by a few studies in patients with drug-resistant epilepsy in which LCM was used as an add-on treatment. To gather knowledge on ASMs effects on sleep, this study aimed at evaluating the effects of LCM monotherapy on sleep in patients with focal epilepsy. Ten patients diagnosed with epilepsy (mean age 58.00 ± 14.77, 60.0% female, mean monthly seizure frequency 1.20 ± 2.48) starting LCM as monotherapy were included. Sleep architecture was assessed through polysomnography at baseline and at the 6-month follow-up visit. A significant decrease was observed in seizure frequency (p = 0.004), being all patients seizure-free at follow-up. At baseline, eight patients had poor sleep efficiency (< 85%). Sleep efficiency increased at follow-up, with only three patients having an index < 85% (p = 0.022). From baseline to follow-up, a significant decrease was observed in sleep latency (p = 0.022) and wakefulness after sleep onset (p = 0.047). Moreover, a significant decrease was observed in the percentage of stage 1 (Md = 6.70 vs Md = 3.85, p = 0.005) and stage 3 (Md = 27.70 vs Md = 22.35, p = 0.01) of Non-REM sleep. This study suggests that LCM monotherapy may positively impact sleep architecture in patients with epilepsy. The sleep efficiency improvement and the decrease of sleep latency and wakefulness after sleep onset observed at follow-up highlight better sleep stability and continuity in patients treated with LCM. Notably, all patients were seizure-free at follow-up, and seizure freedom may also concur to sleep structure improvement.

Sleep-wake cycle and daytime sleepiness in patients with epilepsy after initiating perampanel as adjunctive therapy.

BACKGROUND: Antiseizure medications (ASMs) may affect nocturnal sleep and daytime vigilance. Perampanel (PER), a third-generation ASM, showed to improve nocturnal sleep in patients with epilepsy (PWE). Although ASMs can have beneficial effects on nocturnal sleep and daytime sleepiness, no study investigated the effect of PER on both sleep-wake cycle and daytime sleepiness. Therefore, this study aimed to objectively evaluate the sleep-wake cycle and daytime sleepiness in PWE treated with PER as adjunctive therapy. METHODS: This prospective study included adult PWE who received PER as add-on treatment. Sleep-wake cycle was assessed through actigraphic monitoring and daytime sleepiness by the multiple sleep latency test (MSLT) performed at the end of the actigraphic recording. All patients performed both tests at baseline and at 6-month follow-up. RESULTS: Ten patients (mean age: 44.50 ± 22.71 years, 50.0% female) were included. The mean monthly seizure frequency was 3.20 ± 5.94. Six of ten patients started PER as a first add-on treatment. The final PER dose was 5.11 ± 2.02 mg/day, and nine of ten patients achieved seizure freedom at follow-up. There was a significant decrease in mean monthly seizure frequency from baseline to follow-up (p = 0.004). No significant changes were found in the sleep-wake cycle parameters. An increase in sleep latency mean was observed at MSLT at 6-month follow-up (p = 0.005). CONCLUSIONS: This study confirms that adjunctive PER is effective on seizures without pathologically change of the sleep-wake cycle in PWE and can even improve daytime sleepiness. This effect can be mediated by the achievement of seizure control. Therefore, PER may be promising in PWE with sleep disturbances and daytime sleepiness.

Brainstem impairment in obstructive sleep apnoea and the effect of CPAP treatment: an electrophysiological blink reflex study.

PURPOSE: This study aimed to evaluate the functionality of the brainstem structures through the blink reflex (BR) test in patients with obstructive sleep apnoea (OSA) and to assess the effects of continuous positive airway pressure (CPAP) treatment on BR responses. METHODS: Patients with moderate-severe OSA and controls underwent BR testing. Patients with OSA who were adherent to CPAP therapy repeated BR testing at 6 months follow-up. CPAP adherence was defined as CPAP use for ≥ 4 hour per night on > 5 nights per week with residual apnoea-hypopnea index less than 5 events per hour. RESULTS: A total of 22 patients with OSA (86% male, mean age 57.8 ± 10.6 years) and 20 controls (60% male, mean age 55.3 ± 9.3 years) were included. Patients with OSA showed longer right and left R1 latency, as well as delayed right ipsilateral and contralateral R2 latencies compared to controls. Patients with OSA who were compliant with CPAP treatment (n = 16; 88% men, mean age 58.8 ± 9.7 years) showed a significant decrease in latency of the right ipsilateral and contralateral R2 responses at 6 months. CONCLUSION: This study showed an abnormal pattern of BR responses in patients with OSA, consistent with a significant impairment of brainstem functionality in OSA. CPAP treatment partially improved the BR responses, suggesting the importance of treating OSA.

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.

Depressive symptoms in patients with epilepsy and clinically associated features in a single tertiary center.

Although depressive symptoms are the most common psychiatric comorbidity in epilepsy, they remain underestimated and untreated in a large proportion of patients. The purpose of this study was to evaluate depression severity and related clinical features in people with epilepsy using a well-reliable self-report index of mood, the Beck Depression Inventory-II (BDI-II). One-hundred seventeen adult patients with epilepsy were recruited from a tertiary epilepsy center and completed the BDI-II. A single-item analysis of the 21 questions of the BDI-II was computed and differences between women and men in each depressive symptom were evaluated. Correlation and regression analyses were used to identify clinical features associated with the severity of depression. Results showed gender differences in some items, with women reporting overall higher depression severity than men. The most common symptoms regarded domains of sleeping patterns, tiredness, and loss of energy. Regression evidence suggested that being female, having an epilepsy duration < 10 years, as well as being treated with psychotropic drugs and reporting generalized seizure, were associated with higher depression severity. Despite its cross-sectional nature, this study reinforces the importance of investigating and possibly treating depressive symptoms in adult patients with epilepsy, since they negatively impact well-being, daytime activities, and sleep. Further studies identifying pharmacological and non-pharmacological treatments for depression in epilepsy need to be planned.

Deep brain stimulation in Parkinson's disease patients and routine 6-OHDA rodent models: Synergies and pitfalls.

The history of deep brain stimulation for Parkinson's disease (PD) represented a paradigmatic cross-talk between mammalian disease models and clinical evidence in humans. Fascinating were the results achieved by high frequency stimulation (HFS) into the subthalamic nucleus (STN) of MPTP-treated primates. An analogous strategy relieved tremor and hypokinetic parameters in PD patients. The 6-hydroxydopamine (6-OHDA) rodent model has mastered decades of research, contributing to understanding of the PD pathology. However, this review wonders about the actual synergy between the routine neurotoxic models and PD patients underlying STN-DBS. At first, some findings collected following 6-OHDA, promoted dogmatic visions, as the wrong contention that suppression of STN glutamate was the key therapeutic player. Instead, changes of glutamate release are negligible in humans during transition to ON-state. Besides, the imbalance of basal ganglia endogenous band frequencies, the beta (ß) band increase and the cortical-basal ganglia synchronization, undisputedly shared by models and PD patients, do not govern the whole spectrum of non-motor PD signs, difficult to investigate in rodents. Furthermore, the tonic release of dopamine, inferred during HFS in rodents, was not replicated in humans. Finally, neurotoxic rodent models describe a 'pure' dopamine depletion sparing pathways crucial in parkinsonian phenotypes, that is, noradrenergic and cholinergic ones. Although the utilization of neurotoxic models is still providing major advancements, we pore over these contradictions and try to support possible amendments of neurotoxic models (advocating modern 'in vivo' approaches and recordings extending towards motor thalamus) for pursing the development of new DBS technology.

Sleep-wake cycle dysregulation in idiopathic REM sleep behaviour disorder.

Alteration of the circadian sleep-wake rhythm has been suggested in patients affected by idiopathic rapid eye movement sleep behaviour disorder. Because actigraphy is the validated instrument to monitor the sleep-wake cycle, the aim of the present study was to investigate the circadian sleep-wake rhythm in patients with idiopathic rapid eye movement sleep behaviour disorder compared with healthy aged controls. Fourteen-day actigraphic recording, a comprehensive sleep interview, and cognitive and behavioural domains were investigated in patients affected by idiopathic rapid eye movement sleep behaviour disorder, and compared with controls similar for age, sex and cognitive performances. Patients with idiopathic rapid eye movement sleep behaviour disorder showed reduced relative amplitude and alteration of both sleep and wake compared with controls. Patients with idiopathic rapid eye movement sleep behaviour disorder also showed subjective sleep and wake complaints, and higher scores at the Beck Depression Inventory, compared with controls. Beck Depression Inventory scores correlated with sleep actigraphic parameters, such as sleep latency, sleep efficiency, time in bed, and relative amplitude. Therefore, the present study showed the dysregulation of the sleep-wake cycle in patients with idiopathic rapid eye movement behaviour disorder. Moreover, depressive symptoms documented in patients with idiopathic rapid eye movement sleep behaviour disorder correlated with the sleep-wake rhythm dysregulation.

Subjective neurological symptoms frequently occur in patients with SARS-CoV2 infection.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) represents a novel pneumonia leading to severe acute respiratory syndrome (SARS). Recent studies documented that SARS-Coronavirus2 (SARS-CoV2), responsible for COVID-19, can affect the nervous system. The aim of the present observational study was to prospectively assess subjective neurological symptoms (sNS) in patients with SARS-CoV2 infection. METHODS: We included patients hospitalized at the University Hospital of Rome "Tor Vergata", medical center dedicated to the treatment of patients with COVID-19 diagnosis, who underwent an anamnestic interview about sNS consisting of 13 items, each related to a specific symptom, requiring a dichotomized answer. RESULTS: We included 103 patients with SARS-CoV2 infection. Ninety-four patients (91.3%) reported at least one sNS. Sleep impairment was the most frequent symptom, followed by dysgeusia, headache, hyposmia, and depression. Women more frequently complained hyposmia, dysgeusia, dizziness, numbeness/paresthesias, daytime sleepiness, and muscle ache. Moreover, muscle ache and daytime sleepiness were more frequent in the first 2 days after admission. Conversely, sleep impairment was more frequent in patients with more than 7 days of hospitalization. In these patients we also documented higher white blood cells and lower C-reactive protein levels. These laboratory findings correlated with the occurrence of hyposmia, dysgeusia, headache, daytime sleepiness, and depression. CONCLUSIONS: Patients with SARS-CoV2 infection frequently present with sNS. These symptoms are present from the early phases of the disease. The possibly intrinsic neurotropic properties of SARS-CoV2 may justify the very high frequency of sNS. Further studies targeted at investigating the consequences of SARS-CoV2 infection on the CNS should be planned.

Cognitive performances in patients affected by late-onset epilepsy with unknown etiology: A 12-month follow-up study.

INTRODUCTION: Epilepsy has a growing frequency, particularly in the elderly. Several triggers may cause late-onset epilepsy; however, more than 20% of epilepsies, manifesting in the elderly, has an unknown etiology. Although cognition is frequently altered in patients affected by epilepsy, there is a paucity of studies specifically evaluating cognition in patients affected by late-onset epilepsy. The aim of the present study was to assess the cognitive profile of patients affected by late-onset epilepsy with an unknown etiology and followed for 12 months. METHODS: Patients affected by diagnosed late-onset epilepsy with unknown etiology were included in this observation. All patients were evaluated at the time of diagnosis (baseline) and at follow-up (12 months later). We distributed patients in subgroups based on seizure type (focal seizures [FS], secondarily generalized seizures [SGS], primarily generalized seizures [GS]) and antiepileptic drug (AED) regimen (mono- vs. polytherapy). Cognition was evaluated through standardized neuropsychological testing. RESULTS: Fifty-eight patients were included in this observation and distributed in three groups: 29 affected by FS, 14 affected by SGS, 15 affected by GS. Forty-five patients were in monotherapy, and 13 in polytherapy. The most frequent treatments were levetiracetam (n = 12), valproic acid (VPA) (n = 9), carbamazepine (n = 9), and oxcarbazepine (n = 7). We documented a significant decrease of Mini-Mental State Examination (MMSE) and memory scores at follow-up in the whole group. Verbal learning decreased exclusively in VPA users. CONCLUSION: Patients affected by late-onset epilepsy with unknown etiology showed a significant decline of cognition at follow-up, independently from number and efficacy of AEDs received. These results deserve verification in larger longitudinal cohorts.

Cerebrospinal-fluid biomarkers for predicting phenoconversion in patients with isolated rapid-eye movement sleep behavior disorder.

STUDY OBJECTIVES: Patients with isolated rapid-eye-movement sleep behavior disorder (iRBD) have an increased risk of developing neurodegenerative diseases. This study assessed cerebrospinal-fluid (CSF) biomarkers of neurodegeneration and blood-brain barrier (BBB) alteration in patients with iRBD compared to controls and ascertain whether these biomarkers may predict phenoconversion to alpha-synucleinopathies (Parkinson's Disease (PD), Dementia with Lewy bodies (DLB), Multiple System Atrophy (MSA)). METHODS: Patients and controls underwent between 2012 and 2016 a neurological assessment, a lumbar puncture for CSF biomarker analysis (ß-amyloid42 - Aß42; total-tau, and phosphorylated tau), and BBB alteration (CSF/serum albumin ratio). All patients with iRBD were followed until 2021 and then classified into patients who converted to alpha-synucleinopathies (iRBD converters, cRBD) or not (iRBD non-converters, ncRBD). RESULTS: Thirty-four patients with iRBD (mean age 67.12 ±â€…8.14) and 33 controls (mean age 64.97 ±â€…8.91) were included. At follow-up (7.63 ±â€…3.40 years), eight patients were ncRBD and 33 patients were cRBD: eleven converted to PD, 10 to DLB, and two to MSA. Patients with iRBD showed lower CSF Aß42 levels and higher CSF/serum albumin ratio than controls. Cox regression analysis showed that the phenoconversion rate increases with higher motor impairment (hazard ratio [HR] = 1.23, p = 0.032). CSF Aß42 levels predicted phenoconversion to DLB (HR = 0.67, p = 0.038) and BBB alteration predicted phenoconversion to PD (HR = 1.20, p = 0.038). DISCUSSION: This study showed that low CSF Aß42 levels and high BBB alteration may predict the phenoconversion to DLB and PD in patients with iRBD, respectively. These findings highlight the possibility to discriminate phenoconversion in iRBD patients through CSF biomarkers; however, further studies are needed.

A preliminary study investigating the clinical potential of measuring cerebrospinal-fluid lactate levels in patients with narcolepsy type 1 and 2.

STUDY OBJECTIVES: Besides the quantification of orexin-A/hypocretin-1 cerebrospinal fluid (CSF) levels in narcolepsy for diagnostic purposes, several other CSF biomarkers have been evaluated, although with controversial results. Since CSF lactate concentrations fluctuate according to the sleep-wake cycle with higher levels during wakefulness and lower levels during sleep, as documented in animal model studies, the present study aimed at quantifying the CSF lactate levels in patients with narcolepsy type 1 (NT1) and 2 (NT2), which are two sleep disorders featured by excessive daytime sleepiness (EDS). METHODS: Patients with NT1 and NT2 were enrolled in this study and compared to a control group of similar age and sex. All the subjects included in the study underwent a polysomnographic study followed by lumbar puncture for the quantification of CSF lactate levels at awakening. RESULTS: 23 NT1 (43.5 % male; 36.43 ± 11.89 years) and 15 NT2 patients (46.7 % male; 37.8 ± 14.1 years) were compared to 17 controls (58.8 % male; 32.3 ± 8.4 years). CSF lactate concentrations were reduced in patients with NT1 and NT2 compared to controls but no differences were found between the two groups of patients. ROC curves analysis showed that CSF lactate ≤1.3 mmol/l had a sensitivity of 96.49 and a specificity of 82.35 % for discriminating patients with narcolepsy from controls. CONCLUSIONS: The present study showed a decrease in CSF lactate levels in patients with narcolepsy. Notably, the reduction of lactate levels was present in both NT1 and NT2 patients, independently of CSF orexin levels. Narcolepsy patients present EDS with daytime napping and REM-related episodes, possibly substantiating the CSF lactate levels reduction related to the impaired daytime wakefulness which was demonstrated in animal studies. Moreover, CSF lactate levels present a good sensitivity and adequate specificity for differentiating narcolepsy from controls. Further studies are needed to understand the role of CSF lactate and its usefulness for monitoring daytime vigilance in patients with narcolepsy.

The Sleepiness-Depression Link in Obstructive Sleep Apnea: Preliminary Results on the Mediation of Impulsivity.

BACKGROUND: Emotional impulsivity has been found to be relevant in explaining the association between sleep problems and depressive symptoms, suggesting the potential role of impulsivity as a key underlying mechanism of this link. The objective of this study was to take a preliminary step in understanding the mediating role of impulsivity in the relation between excessive daytime sleepiness (EDS) and depression in patients with obstructive sleep apnea syndrome (OSAS) and to compare psychological and demographic characteristics between different levels of daytime sleepiness. METHODS: A total of 138 patients with OSAS underwent polygraphic cardiorespiratory monitoring and completed a series of questionnaires investigating perceived sleepiness, depression, impulsivity, and other psychological characteristics. A mediational model was tested in order to assess whether impulsivity mediated the relation between sleepiness and depressive symptoms while controlling for the effects of age, sex, BMI, and oxygen saturation parameters. RESULTS: the mediation model showed that there was a significant indirect effect of impulsivity in the sleepiness-depression link (αß = 0.084 [0.0243-0.1617]). CONCLUSIONS: The here-presented results showed that the sleepiness-depression link is not direct as previous studies asserted, but instead it may be better explained by impulsivity. Research and practical implications are discussed.

Exploring the Association Linking Head Position and Sleep Architecture to Motor Impairment in Parkinson's Disease: An Exploratory Study.

Patients with Parkinson's disease (PD) tend to sleep more frequently in the supine position and less often change head and body position during sleep. Besides sleep quality and continuity, head and body positions are crucial for glymphatic system (GS) activity. This pilot study evaluated sleep architecture and head position during each sleep stage in idiopathic PD patients without cognitive impairment, correlating sleep data to patients' motor and non-motor symptoms (NMS). All patients underwent the multi-night recordings, which were acquired using the Sleep Profiler headband. Sleep parameters, sleep time in each head position, and percentage of slow wave activity (SWA) in sleep, stage 3 of non-REM sleep (N3), and REM sleep in the supine position were extracted. Lastly, correlations with motor impairment and NMS were performed. Twenty PD patients (65.7 ± 8.6 y.o, ten women) were included. Sleep architecture did not change across the different nights of recording and showed the prevalence of sleep performed in the supine position. In addition, SWA and N3 were more frequently in the supine head position, and N3 in the supine decubitus correlated with REM sleep performed in the same position; this latter correlated with the disease duration (correlation coefficient = 0.48, p-value = 0.03) and motor impairment (correlation coefficient = 0.53, p-value = 0.02). These preliminary results demonstrated the importance of monitoring sleep in PD patients, supporting the need for preventive strategies in clinical practice for maintaining the lateral head position during the crucial sleep stages (SWA, N3, REM), essential for permitting the GS function and activity and ensuring brain health.

More than sleep and wake disturbances: An actigraphic study showing the sleep-wake pattern dysregulation in epilepsy.

OBJECTIVE: This study aimed to assess the sleep-wake pattern in patients with epilepsy compared to controls. METHODS: Patients with epilepsy and controls underwent a 14-day actigraphic recording to evaluate the rest-activity cycle. A sleep medicine interview was performed to exclude conditions interfering with the sleep-wake cycle in both patients and controls. Patients presenting seizures during the actigraphic recording were excluded. Daytime activity, nocturnal sleep, and non-parametric circadian rhythm activity (NPCRA) were analysed. RESULTS: Twenty-two patients (mean age 49.5 ± 19.84 years; 50% female) and 17 controls were included. Patients showed lower sleep efficiency and longer sleep latency than controls. NPCRA analysis showed lower inter-daily stability and higher intra-daily variability in patients, who also presented lower daytime activity and a longer central phase measure (CPM) than controls. CONCLUSIONS: Patients showed a significant alteration of the sleep-wake pattern, featured by lower synchronization and higher fragmentation of the rest-activity rhythm. Moreover, patients showed a delayed CPM compared with controls, corresponding to an evening chronotype tendency. Nocturnal sleep alteration and lower daytime activity were also evident. Therefore, patients with epilepsy present an alteration of the sleep-wake pattern and clinicians should increase their awareness about circadian rhythmicity dysregulation in epilepsy.

Sleep-disordered breathing and the risk of Alzheimer's disease.

Sleep-disordered breathing is highly prevalent in the elderly population. Obstructive sleep apnea (OSA) represents the most common sleep disorder among the adult and elderly population. Recently, OSA diagnosis has been associated with an increased risk of developing cognitive decline and dementia, including vascular dementia and Alzheimer's disease (AD). Subsequently, there have been studies on AD biomarkers investigating cerebrospinal fluid, blood, neuroimaging, and nuclear medicine biomarkers in patients with OSA. Furthermore, studies have attempted to assess the possible effects of continuous positive airway pressure (CPAP) treatment on the cognitive trajectory and AD biomarkers in patients with OSA. This review summarizes the findings of studies on each AD biomarker (cognitive, biofluid, neuroimaging, and nuclear medicine imaging) in patients with OSA, also accounting for the related effects of CPAP treatment. In addition, the hypothetical model connecting OSA to AD in a bi-directional interplay is analyzed. Finally, the sex-based differences in prevalence and clinical symptoms of OSA between men and women have been investigated in relation to AD risk. Further studies investigating AD biomarkers changes in patients with OSA and the effect of CPAP treatment should be auspicated in future for identifying strategies to prevent the development of AD.

Perampanel Increases Cortical EEG Fast Activity in Child and Adult Patients Affected by Epilepsy: A Quantitative EEG Study.

OBJECTIVE: Quantitative EEG (qEEG) is an established technique used as objective measure for evaluating the effect of antiseizure medications (ASMs) on EEG background activity and monitoring cognitive effects of ASMs. Perampanel (PER) has been associated with relatively more tolerable cognitive effects in patients with epilepsy. The primary aim of the present study was to verify the effect of PER as first add-on ASM on qEEG in child and adult patients affected by epilepsy. The secondary aim of this study was to verify the effectiveness of the drug as first add-on treatment in both child and adult patients with epilepsy. METHODS: We collected data from 17 adults and 10 children treated with PER as first add-on treatment, who underwent qEEG analysis before starting PER and at 3-month follow-up under stable treatment. RESULTS: PER resulted with significant effectiveness in reducing seizures in both children and adults. Considering qEEG analysis, we observed at follow-up the significant increase in beta1 and beta total bands both in children and adult patients. In particular, children showed the significant increase of beta band frequencies predominantly in the occipital regions, whereas adults showed a widespread increase of beta activity. Moreover, we documented in both child and adult patients the global reduction of delta bands activity. CONCLUSIONS: This qEEG study documented the relative increase of cortical EEG fast activity in both children and adult patients affected by epilepsy and treated by PER. This result may suggest a potential less negative impact of PER on cognition in patients affected by epilepsy, other than demonstrating effectiveness of the drug when used as first add-on treatment in both children and adult patients.

Sleep disorders and late-onset epilepsy of unknown origin: Understanding new trajectories to brain amyloidopathy.

The intertwining between epilepsy, sleep disorders and beta amyloid pathology has been progressively highlighted, as early identification and stratification of patients at high risk of cognitive decline is the need of the hour. Modification of the sleep-wake activity, such as sleep impairment or excessive daytime sleepiness, can critically affect cerebral beta amyloid levels. Both mice models and human studies have demonstrated a substantial increase in the burden of beta amyloid pathology after sleep-deprivation, with potential negative effects partially restored by sleep recovery. The accumulation of beta amyloid has been shown to be an early event in the course of Alzheimer's disease dementia. Beta amyloid accumulation has been linked to epileptic seizures epileptic seizures, with beta amyloid being itself pro-epileptogenic in mice models already at oligomeric stage, well before plaque deposition. Further supporting a potential relationship between beta amyloid and epilepsy: i) seizures happen in 1 out of oofut 10 patients with Alzheimer's disease in the prodromal stage, ii) epileptic activity accelerates cognitive decline in Alzheimer's disease, iii) people with late-onset epilepsy present a critically high risk of developing dementia. In this Review we highlight the role of beta amyloid as a potential shared mechanisms between sleep disorders, late-onset epilepsy, and cognitive decline.

Sleep problems affect quality of life in Parkinson's disease along disease progression.

OBJECTIVES: Non-motor symptoms (NMS) frequently impact health-related quality of life (HRQoL) in patients with Parkinson's Disease (PD). Sleep problems represent one of the main NMS complained by PD patients. In this observation study, sleep problems measured by Parkinson's Disease Sleep Scale - 2nd version (PDSS-2), and HRQoL measured by Parkinson's Disease Questionnaire-39 (PDQ39) were quantified in patients with PD ranging from mild to moderate-advanced disease stages, and correlated to motor impairment and anti-PD therapy. METHODS: We included idiopathic PD patients who underwent PDSS-2 and PDQ39. Moreover, we assessed patients' motor symptoms by rating the Unified Parkinson's Disease Rating Scale (UPDRS) - III section (motor examination), patients' PD status following H&Y stage, and levodopa equivalent daily dose (LEDD). RESULTS: One-hundred and fifty-four patients with PD were included and distributed for H&Y stage. PDSS-2 and PDQ39 total and sub-items scores significantly increased with the H&Y stage. PDSS-2 total score significantly correlated with PDQ39 total score (γ = 0.63, P < 0.01). Finally, distributing PD patients according to the PDSS-2 cut-off for detecting sleep disturbances, we found in poor sleepers (n = 58) higher PDQ39 scores than good sleepers (n = 89). CONCLUSIONS: Sleep problems are very common in patients with PD and severely impact on HRQoL. Sleep impairment and low HRQoL occur from the early stages of the disease and deteriorate along disease progression. Further studies investigating sleep and quality of life should be planned for targeting sleep improvement to increase HRQoL and possibly reduce motor impairment.