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Background: Idiopathic rapid eye movement sleep behavior disorder (iRBD) represents the prodromal stage of cit-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 [F-18]FDG-PET (F-18-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. [F-18]FDG-PET pattern analysis has potential as a phenoconversion biomarker in iRBD patients. (C) 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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.

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) in myotonic dystrophy type 1 is mostly of central origin but it may coexist with sleep-related breathing disorders. However, there is no consensus on the sleep protocols to be used, assessments vary, and only a minority of patients are regularly tested or are on treatment for EDS. Our study presents data on self-reported and objective EDS in adult-onset myotonic dystrophy type 1. METHODS: Sixty-three patients with adult-onset DM1 were subjected to EDS-sleep assessments (polysomnography, Multiple Sleep Latency Test, Epworth Sleepiness Scale). Correlation coefficients were computed to assess the relationship between sleep and sleepiness test results, fatigue, and quality of life. RESULTS: 33% and 48% of patients had EDS based, respectively, on the Epworth Sleepiness Scale and the Multiple Sleep Latency Test, with a low concordance between these tests (k = 0.19). Thirteen patients (20%) displayed 2 or more sleep-onset rapid eye movement periods on Multiple Sleep Latency Test. Patients having EDS by Multiple Sleep Latency Test had a shorter disease duration (P < .05), higher total sleep time and sleep efficiency and lower wake after sleep onset on polysomnography. Patients with self-reported EDS reported significantly higher fatigue score compared with patients without EDS (P < .05). No other difference was found in demographic, clinical, and respiratory features. CONCLUSIONS: EDS test results are contradictory, making treatment options difficult. Combining quantitative tests and self-reported scales may facilitate physicians in planning EDS care with patients and families. CITATION: Sansone VA, Proserpio P, Mauro L, et al. Assessment of self-reported and objective daytime sleepiness in adult-onset myotonic dystrophy type 1. J Clin Sleep Med. 2021;17(12):2383–2391.

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.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.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).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.

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.

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.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 HY stage, and levodopa equivalent daily dose (LEDD).One-hundred and fifty-four patients with PD were included and distributed for HY stage. PDSS-2 and PDQ39 total and sub-items scores significantly increased with the HY 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).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.

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.

This study aimed to assess the sleep-wake pattern in patients with epilepsy compared to controls.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.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.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.

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.

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 (β) 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.

Study objectives The present study aimed at identifying the sleep-wake rhythm in patients with myotonic dystrophy type 1 (DM1) compared to healthy controls. Methods Patients with genetic diagnosis of DM1 and healthy controls underwent a 7-day actigraphic recording and filled out a daily sleep diary to evaluate the sleep-wake rhythm. All participants underwent a physical and neurological examination to exclude conditions interfering with the sleep-wake cycle. Daytime activity, nocturnal sleep, and non-parametric circadian rhythm activity (NPCRA) were analysed. Results Twenty-nine patients affected by DM1 were included in the present study and were compared to 16 controls. Considering nocturnal actigraphic data, DM1 patients showed a longer time in bed, sleep period time, actual sleep time, and sleep latency compared to controls. Central phase measurement was significantly longer in DM1 patients than controls. At NPCRA analysis patients showed a lower degree of regularity in the activity-rest pattern compared to controls. Moreover, DM1 patients showed reduced motor activity during daytime and a lower synchronization of the rest-activity rhythm than controls. Conclusions This study documented that patients with DM1 not only present the impairment of nocturnal sleep, but also show a dysregulation of the sleep-wake circadian rhythm; moreover, reduced amplitude of the circadian rhythmicity was also evident in comparison to controls, probably in relation to the reduced diurnal motor activity of patients. These findings add further evidence to the already documented sleep impairment and excessive daytime sleepiness in DM1 patients.

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.

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.

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.

Background Alzheimer's disease (AD) is the most common form of dementia. It is mainly characterized by a progressive deterioration of cognition, but sleep-wake cycle disturbances frequently occur. Irregular sleep-wake cycle, insomnia, and daytime napping usually occur in patients with AD in the course of the disease. Objective The aim of the present study was to verify the sleep-wake cycle in mild to moderate AD patients compared to controls, and to evaluate the relationship between the sleep-wake cycle impairment and the neuropsychological testing, CSF AD biomarkers, and CSF orexin concentrations. Methods Mild to moderate AD patients were enrolled and underwent 14-day actigraphic recording, sleep diary, neuropsychological testing, and CSF biomarkers analysis. All patients were compared to controls. Results Eighteen AD patients were compared to ten controls. AD patients showed the alteration of the sleep-wake cycle, featured by sleep dysregulation and daytime wake fragmentation, with respect to controls. Considering the correlation analysis, we documented the correlation between tau proteins and orexin CSF levels and sleep-wake cycle dysregulation. Conclusion This study confirmed the dysregulation of sleep-wake cycle in AD patients, as reflected by the daytime wake fragmentation, irregular sleep-wake rhythm, and nocturnal sleep impairment. This sleep-wake cycle disorder correlates with AD neuropathological in vivo features and brain orexin activity. Hence, we suppose that a more marked AD pathology coupled with orexinergic system dysregulation may promote sleep-wake cycle impairment in AD patients.

Background Alzheimer's disease (AD) is frequently accompanied by sleep impairment, which can induce AD-related neurodegeneration. We herein investigated the sleep architecture, cognition, and cerebrospinal fluid (CSF) biomarkers (tau proteins and β-amyloid42) during AD progression from subjective cognitive impairment (SCI) to mild cognitive impairment (MCI) and eventually to AD dementia, and compared the results with cognitively normal (CN) subjects. Methods We included patients affected by SCI, MCI, mild AD, and moderate-to-severe AD in our study along with CN subjects as controls. All the subjects underwent nocturnal polysomnography to investigate sleep, neuropsychological testing to evaluate cognition, and lumbar puncture for CSF AD biomarkers assessment. Results Sleep (both rapid eye movement (REM) and non-REM sleep) and memory function are both progressively impaired during the course of AD from SCI to mild and subsequently to moderate AD. Further, sleep dysregulation appears earlier than cognitive deterioration, with a reduction of CSF β-amyloid42 level. Conclusion Sleep, memory, and CSF AD biomarkers are closely interrelated in AD progression from the earliest asymptomatic and preclinical stages of the disease related in AD since the earliest and preclinical stages of the disease.

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.

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.