Optogenetic targeting of cortical astrocytes selectively improves NREM sleep in an Alzheimer's disease mouse model.

Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by memory impairments and distinct histopathological features such as amyloid-beta (Aß) accumulations. Alzheimer's patients experience sleep disturbances at early stages of the disease. APPswe/PS1dE9 (APP) mice exhibit sleep disruptions, including reductions in non-rapid eye movement (NREM) sleep, that contribute to their disease progression. In addition, astrocytic calcium transients associated with a sleep-dependent brain rhythm, slow oscillations prevalent during NREM sleep, are disrupted in APP mice. However, at present it is unclear whether restoration of circuit function by targeting astrocytic activity could improve sleep in APP mice. To that end, APP mice expressing channelrhodopsin-2 (ChR2) targeted to astrocytes underwent optogenetic stimulation at the slow oscillation frequency. Optogenetic stimulation of astrocytes significantly increased NREM sleep duration but not duration of rapid eye movement (REM) sleep. Optogenetic treatment increased delta power and reduced sleep fragmentation in APP mice. Thus, optogenetic activation of astrocytes increased sleep quantity and improved sleep quality in an AD mouse model. Astrocytic activity provides a novel therapeutic avenue to pursue for enhancing sleep and slowing AD progression.

Using cross-recurrence quantification analysis to compute similarity measures for time series of unequal length with applications to sleep stage analysis.

Comparing time series of unequal length requires data processing procedures that may introduce biases. This article describes, validates, and applies Cross-Recurrence Quantification Analysis (CRQA) to detect and quantify correlation and coupling among time series of unequal length without prior data processing. We illustrate and validate this application using continuous and discrete data from a model system (study 1). Then we use the method to re-analyze the Sleep Heart Health Study (SHHS), a rare large dataset comprising detailed physiological sleep measurements acquired by in-home polysomnography. We investigate whether recurrence patterns of ultradian NREM/REM sleep cycles (USC) predict mortality (study 2). CRQA exhibits better performance compared with traditional approaches that require trimming, stretching or compression to bring two time series to the same length. Application to the SHHS indicates that recurrence patterns linked to stability of USCs are associated with all-cause mortality even after controlling for other sleep parameters, health, and sociodemographics. We suggest that CRQA is a useful tool for analyzing categorical time series, where the underlying structure of the data is unlikely to result in matching data points-such as ultradian sleep cycles.

Corrigendum: L-DOPA increases slow-wave sleep duration and selectively modulates memory persistence in older adults.

[This corrects the article DOI: 10.3389/fnbeh.2023.1096720.].

Fluoxetine, but not paroxetine, alters the jaw-closing muscle activity during non-rapid eye movement sleep in mice.

Sleep bruxism is an involuntary, exaggerated jaw-closing activity during sleep. Selective serotonin reuptake inhibitor (SSRI) use is a risk factor for bruxism. However, the effect of various SSRIs on masseter (jaw-closing) muscle activity remains unclear. Here, we examined the effects of long-term administration of two SSRIs, fluoxetine (FLX) and paroxetine (PRX), for 14 days on masseter muscle activity during wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep for 24 h in mice. Vigilance states were scored based on electroencephalographic, electrooculography and neck electromyographic (EMG) activities. The EMG activity of the masseter muscle was quantified in 6 h periods. FLX and PRX did not affect the duration of the three vigilance states. Both drugs significantly prolonged the REM sleep episode duration while decreasing the number of episodes. FLX significantly increased REM sleep onset latency. Neither FLX nor PRX affected the mean masseter EMG activity during wakefulness. FLX significantly increased the relative time of masseter muscle activity in NREM sleep during 02:00-08:00 and 08:00-14:00, while PRX did not affect three vigilance states. Overall, FLX had a limited but significant effect on masseter muscle activity in NREM sleep during specific periods.

Restoration of abnormal sleep EEG power in patients with insomnia disorder after 1Hz rTMS over left DLPFC.

Introduction: Hyperarousal has been a significant pathophysiological theory related to insomnia disorder (ID), characterized by excessive cortical activation and abnormal electroencephalogram (EEG) power during daytime or sleep. However, there is currently insufficient attention to the EEG power during rapid eye movement (REM) sleep and different stages of non-rapid eye movement (NREM) sleep. Additionally, whether the abnormal sleep EEG power in ID patients can be restored by repetitive transcranial magnetic stimulation (rTMS) remains unclear. Methods>: Data of 26 ID patients and 26 healthy controls (HCs) were included in the current observational study. The comparisons of relative power between patients and HCs at baseline in each band of each sleep stage and the changes in patients before and after rTMS treatment were performed. The correlations between relative power and behavioral measures of the patients were also investigated. Results: Abnormalities in sleep EEG relative power in the delta, beta and gamma bands of the patients were observed in NREM2, NREM3 and REM sleep. Correlations were identified between relative power and behavioral measures in ID group, primarily encompassing sleep efficiency, sleep onset latency and depression scores. Post-treatment improvements in relative power of the delta and beta band were observed in NREM2 sleep. Discussion: The relative power of sleep EEG exhibited a significant correlation with sleep measures in ID patients, and demonstrated notable differences from HCs across the delta, beta, and gamma frequency bands. Furthermore, our findings suggest that rTMS treatment may partially ameliorate relative power abnormalities in patients with ID.

A predictive propensity measure to enter REM sleep.

Introduction: During sleep periods, most mammals alternate multiple times between rapid-eye-movement (REM) sleep and non-REM (NREM) sleep. A common theory proposes that these transitions are governed by an "hourglass-like" homeostatic need to enter REM sleep that accumulates during the inter-REM interval and partially discharges during REM sleep. However, markers or mechanisms for REM homeostatic pressure remain undetermined. Recently, an analysis of sleep in mice demonstrated that the cumulative distribution function (CDF) of the amount of NREM sleep between REM bouts correlates with REM bout duration, suggesting that time in NREM sleep influences REM sleep need. Here, we build on those results and construct a predictive measure for the propensity to enter REM sleep as a function of time in NREM sleep since the previous REM episode. Methods: The REM propensity measure is precisely defined as the probability to enter REM sleep before the accumulation of an additional pre-specified amount of NREM sleep. Results: Analyzing spontaneous sleep in mice, we find that, as NREM sleep accumulates between REM bouts, the REM propensity exhibits a peak value and then decays to zero with further NREM accumulation. We show that the REM propensity at REM onset predicts features of the subsequent REM bout under certain conditions. Specifically, during the light phase and for REM propensities occurring before the peak in propensity, the REM propensity at REM onset is correlated with REM bout duration, and with the probability of the occurrence of a short REM cycle called a sequential REM cycle. Further, we also find that proportionally more REM sleep occurs during sequential REM cycles, supporting a correlation between high values of our REM propensity measure and high REM sleep need. Discussion: These results support the theory that a homeostatic need to enter REM sleep accrues during NREM sleep, but only for a limited range of NREM sleep accumulation.

Differential effects of sleep deprivation on sleepwalking: Role of demographic and clinical profiles.

BACKGROUND: Although sleepwalking is one of the most prevalent and potentially injurious of the NREM parasomnias, it is still diagnosed primarily based on the patient's clinical history. Early pilot work suggested that sleep deprivation protocols could help obtain a polysomnographically-based (PSG) diagnosis of sleepwalking, but larger studies remain lacking. METHODS: We compared baseline PSG recordings with those obtained after 25hrs of sleep deprivation in a cohort of 124 consecutively assessed adult sleepwalkers. RESULTS: When compared to baseline recordings, post-sleep deprivation PSG assessments resulted in nearly twice as many somnambulistic episodes being recorded in the laboratory and significantly increased the proportion of patients (from 48 % to 63 %) experiencing at least one lab-based episode. Moreover, while 17 % of patients experienced a sleepwalking event exclusively during recovery sleep, only 2 % of patients did so solely at baseline. Sleep deprivation had similar facilitating effects on patents' somnambulistic events regardless of age of onset and positive versus negative family history for sleepwalking. Younger age and higher home episode frequency both predicted a positive response to sleep deprivation. A separate group of 17 patients with comorbid sleep disorders showed a similar increase in their proportion experiencing at least one episode during recovery sleep. CONCLUSION: The results from this large series of sleepwalkers provide strong support for the use of sleep deprivation in facilitating the occurrence of somnambulistic events in the sleep laboratory.

NREM parasomnia-related behaviors and adverse childhood experiences.

PURPOSE: To assess the prevalence, types, sociodemographic factors, and reported dangerous activities of sleep-related behaviors likely representing NREM parasomnia episodes, as well as their association with adverse childhood experiences in Hungary. METHODS: Cross-sectional survey of 1000 adults (aged ≥18 years) representing the Hungarian population, using a non-probability quota sampling with a random walk method and a structured face-to-face interview. A multi-criterion weighting procedure was applied to correct bias along the main sociodemographic variables to the data available. Binary logistic regression estimated the odds of NREM parasomnia-related behaviors associated with sociodemographic factors and adverse childhood experiences. RESULTS: The prevalence of NREM parasomnia-related behaviors was 2.7 %, and self-reported sleep-eating was 0.1 % of the population (4.6 % of parasomnia-like activities). For middle-aged adults, the odds of sleep ambulation were significantly lower than for younger adults (OR 0.3; P = 0.03). A participant's family occurrence of reported parasomnia-like activity increased their odds of having it by more than 7 times (OR 7.1; P < 0.001). Nine participants out of those 27 people reporting NREM parasomnia-related behavior episodes, reported childhood adverse experiences, increasing the odds of parasomnia-related behavior by more than six times (OR 6.2; P < 0.001) compared to those not reporting it. CONCLUSION: This is the first population survey in Hungary on adult sleep-related behaviors likely representing NREM parasomnia episodes and the potential association with childhood traumatic events preceding them. The related dangerous behaviors call for safety measures and prevention. The significant association between adverse childhood events and NREM parasomnia-related behaviors needs further analysis.

Effects of post-learning nap in the recognition memory for faces in habitual nappers.

This study investigated the effects of diurnal nap in the recognition memory for faces in habitual nappers. Thirty volunteers with habitual midday napping (assigned as the sleep group) and 28 non-nappers (assigned as the wake group) participated in this study. Participants were instructed to memorize faces, and subsequently to perform two recognition tasks before and after nap/wakefulness, i.e., an immediate recognition and a delayed recognition. There were three experimental conditions: same faces with the same view angle (S-S condition); same faces with a different view angle (22.5°) (S-D condition); and novel faces (NF condition). A mixed repeated-measures ANOVA revealed that the sleep group exhibited significantly longer reaction times (RT) following their nap compared to those of the wake group; no significant between-group differences were observed in accuracy or sensitivity (d'). Furthermore, both groups were more conservative in the delayed recognition task compared to the immediate recognition task, but the sleep group was more conservative after their nap (vs pre-nap), reflected by the criterion (ß, Ohit/Ofalse alarm). Further stepwise regression analysis revealed a positive relationship between duration of stage N3 sleep and normalized RT difference before/after nap on the S-S condition. These findings suggest that an immediate nap following face learning is associated with memory reorganization during N3 sleep in habitual nappers, rendering the memories not readily accessible.

Aversive memories can be weakened during human sleep via the reactivation of positive interfering memories.

Recollecting painful or traumatic experiences can be deeply troubling. Sleep may offer an opportunity to reduce such suffering. We developed a procedure to weaken older aversive memories by reactivating newer positive memories during sleep. Participants viewed 48 nonsense words each paired with a unique aversive image, followed by an overnight sleep. In the next evening, participants learned associations between half of the words and additional positive images, creating interference. During the following non-rapid-eye-movement sleep, auditory memory cues were unobtrusively delivered. Upon waking, presenting cues associated with both aversive and positive images during sleep, as opposed to not presenting cues, weakened aversive memory recall while increasing positive memory intrusions. Substantiating these memory benefits, computational modeling revealed that cueing facilitated evidence accumulation toward positive affect judgments. Moreover, cue-elicited theta brain rhythms during sleep predominantly predicted the recall of positive memories. A noninvasive sleep intervention can thus modify aversive recollection and affective responses.

Impact of Pre-Sleep Visual Media Exposure on Dreams: A Scoping Review.

A body of experimental research has aimed to investigate processes underlying dream formation by examining the effects of a range of pre-sleep stimuli and events on subsequent dream content. Given its ever-growing presence and salience in people's everyday lives, pre-sleep media consumption stands out as a key variable that could influence people's dreams. We conducted a scoping review to evaluate the experimental evidence of the effects of pre-sleep exposure to visual media on dream content. A systematic search on PubMed, PsycInfo, and Web of Science using terms related to moving visual media and dreams yielded 29 studies meeting the inclusion criteria. Overall, we found modest yet varied effects of pre-sleep exposure to visual media on dream content, with rates of stimulus-related incorporation ranging from 3% to 43% for REM dream reports, 4% to 30% for NREM sleep mentation reports, and between 11% and 35% for home dream reports. Our review highlights the large methodological heterogeneity and gaps across studies, the general difficulty in influencing dream content using pre-sleep exposure to visual media, and suggests promising venues for future research to advance our understanding of how and why digital media may impact people's dreams.

NREM sleep brain networks modulate cognitive recovery from sleep deprivation.

Decrease in cognitive performance after sleep deprivation followed by recovery after sleep suggests its key role, and especially non-rapid eye movement (NREM) sleep, in the maintenance of cognition. It remains unknown whether brain network reorganization in NREM sleep stages N2 and N3 can uniquely be mapped onto individual differences in cognitive performance after a recovery nap following sleep deprivation. Using resting state functional magnetic resonance imaging (fMRI), we quantified the integration and segregation of brain networks during NREM sleep stages N2 and N3 while participants took a 1-hour nap following 24-hour sleep deprivation, compared to well-rested wakefulness. Here, we advance a new analytic framework called the hierarchical segregation index (HSI) to quantify network segregation across spatial scales, from whole-brain to the voxel level, by identifying spatio-temporally overlapping large-scale networks and the corresponding voxel-to-region hierarchy. Our results show that network segregation increased in the default mode, dorsal attention and somatomotor networks during NREM sleep compared to wakefulness. Segregation within the visual, limbic, and executive control networks exhibited N2 versus N3 sleep-specific voxel-level patterns. More segregation during N3 was associated with worse recovery of working memory, executive attention, and psychomotor vigilance after the nap. The level of spatial resolution of network segregation varied among brain regions and was associated with the recovery of performance in distinct cognitive tasks. We demonstrated the sensitivity and reliability of voxel-level HSI to provide key insights into within-region variation, suggesting a mechanistic understanding of how NREM sleep replenishes cognition after sleep deprivation.

Sleep loss impairs blood-brain barrier function: Cellular and molecular mechanisms.

Sleep is a physiological process that preserves the integrity of the neuro-immune-endocrine network to maintain homeostasis. Sleep regulates the production and secretion of hormones, neurotransmitters, cytokines and other inflammatory mediators, both at the central nervous system (CNS) and at the periphery. Sleep promotes the removal of potentially toxic metabolites out of the brain through specialized systems such as the glymphatic system, as well as the expression of specific transporters in the blood-brain barrier. The blood-brain barrier maintains CNS homeostasis by selectively transporting metabolic substrates and nutrients into the brain, by regulating the efflux of metabolic waste products, and maintaining bidirectional communication between the periphery and the CNS. All those processes are disrupted during sleep loss. Brain endothelial cells express the blood-brain barrier phenotype, which arises after cell-to-cell interactions with mural cells, like pericytes, and after the release of soluble factors by astroglial endfeet. Astroglia, pericytes and brain endothelial cells respond differently to sleep loss; evidence has shown that sleep loss induces a chronic low-grade inflammatory state at the CNS, which is associated with blood-brain barrier dysfunction. In animal models, blood-brain barrier dysfunction is characterized by increased blood-brain barrier permeability, decreased tight junction protein expression and pericyte detachment from the capillary wall. Blood-brain barrier dysfunction may promote defects in brain clearance of potentially neurotoxic metabolites and byproducts of neural physiology, which may eventually contribute to neurodegenerative diseases. This chapter aims to describe the cellular and molecular mechanisms by which sleep loss modifies the function of the blood-brain barrier.

Heukharang (Lactuca sativa L.) extracts enhanced the sleep behavior of mice: potential involvement of adenosine A1 and A2A receptors.

A significant proportion of the world's population suffers from insomnia, a disorder characterized by complications in initiating and maintaining sleep. Many medications used to treat insomnia target the γ-aminobutyric acid (GABA) neurotransmitter system. However, these substances, such as benzodiazepines, induce significant adverse consequences, including dependence and memory impairment, after prolonged use. Thus, current studies are aimed at developing therapeutic hypnotics derived from natural sources that may cause less severe side effects. Heukharang is a variety of lettuce from Korea that was discovered to contain sleep-promoting compounds. Therefore, we investigated the potential effects of sub-chronic administration of Heukharang extract (FSD-LS) on sleep behavior (pentobarbital-induced sleeping test), brain wave activity and sleep architecture (electroencephalography), and physiological behavior (open-field test and rota-rod) in mice, along with radioligand binding assays (GABAA, adenosine A1 and A2A receptors). We found that FSD-LS prolonged the total sleep duration and reduced the onset time of sleep, and enhanced delta wave power and non-rapid eye movement (NREM) sleep duration, all indicating persistent sleep-enhancing effects. FSD-LS lacked adverse effects on the spontaneous locomotor activity and motor coordination of mice, unlike diazepam. Pharmacological blocking using caffeine and bicuculline supported the possible involvement of adenosine receptors in the sleep-promoting effects of FSD-LS, with partial contribution from GABA receptor activity. Overall, our study recommends FSD-LS as a potential source for the development of sleep-aiding therapeutics.

Hypnotic treatment improves sleep architecture and EEG disruptions and rescues memory deficits in a mouse model of fragile X syndrome.

Fragile X syndrome (FXS) is associated with disrupted cognition and sleep abnormalities. Sleep loss negatively impacts cognitive function, and one untested possibility is that disrupted cognition in FXS is exacerbated by abnormal sleep. We tested whether ML297, a hypnotic acting on G-protein-activated inward-rectifying potassium (GIRK) channels, could reverse sleep phenotypes and disrupted memory in Fmr1-/y mice. Fmr1-/y mice exhibit reduced non-rapid eye movement (NREM) sleep and fragmented NREM architecture, altered sleep electroencephalogram (EEG) oscillations, and reduced EEG coherence between cortical areas; these are partially reversed following ML297 administration. Treatment following contextual fear or spatial learning restores disrupted memory consolidation in Fmr1-/y mice. During memory recall, Fmr1-/y mice show an altered balance of activity among hippocampal principal neurons vs. parvalbumin-expressing interneurons; this is partially reversed by ML297. Because sleep disruption could impact neurophysiological phenotypes in FXS, augmenting sleep may improve disrupted cognition in this disorder.

The clinical characteristic of catathrenia: a new look at an old issue-a systematic review of existing literature.

STUDY OBJECTIVES: The International Classification of Sleep Disorders categorized catathrenia as a respiratory disorder, but there are doubts whether episodes appear during rapid eye movement (REM) sleep or the non-rapid eye movement (NREM), their duration, and symptoms. The main objectives were to identify the most common features and relations of catathrenia. METHODS: PubMed, Embase, and Web of Science were searched according to the PRISMA 2020 guidelines. The Joanna Briggs Institute and the ROBINS-I tools were chosen to assess the risk of bias. RESULTS: A total of 288 records were identified, 31 articles were included. The majority of the studies had a moderate risk of bias. 49.57% of episodes occurred during the NREM sleep, while 46% took place during REM. In 60.34% females, catathrenia was more common in the NREM, while in 59.26% of males was in REM sleep (p < 0.05). Females and obese individuals were found to have shorter episodes (p < 0.05). Age was inversely correlated with minimal episodes duration (r = - 0.34). The continuous positive airway pressure (CPAP) therapy was inversely correlated with the maximal episode duration (r = - 0.48). CONCLUSIONS: Catathrenia occurs with similar frequency in both genders. The most frequent symptoms embraced groaning, awareness of disturbing bedpartners, and daytime somnolence-not confirmed by the Epworth Sleepiness Scale. The episodes occur more frequently in NREM than in REM sleep. Catathrenia may be considered as a sex-specific condition. The effects of CPAP treatment leading to shortening episodes duration, which may indicate the respiratory origin of catathrenia.

Una Caracterización de la Arquitectura del Sueño en Adultos con Bruxismo del Sueño: Un Estudio Descriptivo Retrospectivo / Characterization of Sleep Architecture in Adults with Sleep Bruxism: A Retrospective Descriptive Study

Objetivo: Caracterizar la arquitectura del sueño en un grupo poblacional de adultos con bruxismo del sueño, en forma general y según sexo.Materiales y método: Estudio descriptivo retrospectivo, con un muestreo por intención de 33 polisomnografías que identificaban sujetos con bruxismo del sueño, según el “cut off” sugerido por Lavigne et al (25 eventos /hora), entre los años 2011-2019. Se consideraron las variables sexo, edad, peso, talla e índice de masa corporal (IMC). Se determinó la arquitectura del sueño en cuanto a duración de las etapas del sueño, micro despertares y eventos de bruxismo. Se realizó un análisis descriptivo de las variables y se compraron los resultados entre los sexos.Resultados: En el grupo poblacional 64% eran mujeres y 36% hombres. El promedio de edad fue de 32.5 años, de talla 1.65, de peso 68 kg, con un IMC promedio de 24.89 (peso normal). Los sujetos tuvieron un promedio de 387.6 horas de sueño, 270 minutos en NMOR y 10.8 en MOR, con un promedio de 50 micro despertares durante la noche y de 48.64 eventos de bruxismo por hora. Según sexo los valores en minutos fueron (p>0.05): NMOR (H: 316.2 – M:256.8); MOR (H: 105 – M:104.4); microdespertares (H :58.9 – M: 45.1); Eventos de BS/hora: (H:48.6 – M: 46.6) Los sujetos con BS durmieron, en promedio, un mayor número de minutos en decúbito lateral (196,59).Conclusión: Los sujetos con BS registran determinadas características en la arquitectura del sueño que deben considerarse. No hubo diferencia en la arquitectura del sueño según sexo. (AU)

Objective: To characterize sleep architecture in a population group of adults with sleep bruxism, in general and by sex. Materials and method: Retrospective descriptive study, with intentional sampling of 33 polysomnographies that identified subjects with sleep bruxism,according to the “cut off” suggested by Lavigne et al (25 events /hour/), between the years 2011-2019. The variables sex, age, weight, height and body mass index (BMI) were considered. Sleep architecture was determined in terms of duration of sleep stages, micro-awakenings, and bruxism events. A descriptive anlysis of the variables was carried out and the results were compared between the sexes.Results: In the population group, 64% were women and 36% men. The average age was 32.5 years, height 1.65 m, weight 68 kg, with an average BMI of 24.89 (normal weight). Subjects had an average of 387.6 minutes of sleep, 270 minutes in non-rapid eye movement (NREM) and 10.8 in rapid eye movement (REM), with an average of 50 micro-awakenings during the night and 48.64 bruxism events per hour. According to sex, the values in minutes were: NMOR (H:316.2 – M:256.8); MOR (H:105 – M:104.4); microawakenings (H:58.9 – M:45.1); BS events/hour: (H:48.6 – M: 46.6), no significant differences were found between them (p>0.05). Subjects with BS slept, on average, a greater number of minutes in the lateral decubitus position (196.59). Conclusion: Subjects with BS register certain characteristics in their sleep architecture that must be considered. There was no difference in sleeparchitecture according to sex.(AU)

Memory Reactivation during Sleep Does Not Act Holistically on Object Memory.

Memory reactivation during sleep is thought to facilitate memory consolidation. Most sleep reactivation research has examined how reactivation of specific facts, objects, and associations benefits their overall retention. However, our memories are not unitary, and not all features of a memory persist in tandem over time. Instead, our memories are transformed, with some features strengthened and others weakened. Does sleep reactivation drive memory transformation? We leveraged the Targeted Memory Reactivation technique in an object category learning paradigm to examine this question. Participants (20 female, 14 male) learned three categories of novel objects, where each object had unique, distinguishing features as well as features shared with other members of its category. We used a real-time EEG protocol to cue the reactivation of these objects during sleep at moments optimized to generate reactivation events. We found that reactivation improved memory for distinguishing features while worsening memory for shared features, suggesting a differentiation process. The results indicate that sleep reactivation does not act holistically on object memories, instead supporting a transformation where some features are enhanced over others.

Differences in sleep spindle wave density between patients with diabetes mellitus and matched controls: implications for sensing and regulation of peripheral blood glucose.

Background: Brain waves during sleep are involved in sensing and regulating peripheral glucose level. Whether brain waves in patients with diabetes differ from those of healthy subjects is unknown. We examined the hypothesis that patients with diabetes have reduced sleep spindle waves, a form of brain wave implicated in periphery glucose regulation during sleep. Methods: From a retrospective analysis of polysomnography (PSG) studies on patients who underwent sleep apnea evaluation, we identified 1,214 studies of patients with diabetes mellitus (>66% type 2) and included a sex- and age-matched control subject for each within the scope of our analysis. We similarly identified 376 patients with prediabetes and their matched controls. We extracted spindle characteristics from artifact-removed PSG electroencephalograms and other patient data from records. We used rank-based statistical methods to test hypotheses. We validated our finding on an external PSG dataset. Results: Patients with diabetes mellitus exhibited on average about half the spindle density (median=0.38 spindles/min) during sleep as their matched control subjects (median=0.70 spindles/min) (P<2.2e-16). Compared to controls, spindle loss was more pronounced in female patients than in male patients in the frontal regions of the brain (P=0.04). Patients with prediabetes also exhibited signs of lower spindle density compared to matched controls (P=0.01-0.04). Conclusions: Patients with diabetes have fewer spindle waves that are implicated in glucose regulation than matched controls during sleep. Besides offering a possible explanation for neurological complications from diabetes, our findings open the possibility that reversing/reducing spindle loss could improve the overall health of patients with diabetes mellitus.