Are age and sex effects on sleep slow waves only a matter of EEG amplitude ?

Aging is associated with reduced slow wave (SW) density (number SW/min in nonrapid-eye movement sleep) and amplitude. It has been proposed that an age-related decrease in SW density may be due to a reduction in electroencephalogram (EEG) amplitude instead of a decline in the capacity to generate SW. Here, we propose a data-driven approach to adapt SW amplitude criteria to age and sex. We predicted that the adapted criteria would reduce age and sex differences in SW density and SW characteristics but would not abolish them. A total of 284 healthy younger and older adults participated in one night of sleep EEG recording. We defined age- and sex-adapted SW criteria in a first cohort of younger (n = 97) and older (n = 110) individuals using a signal-to-noise ratio approach. We then used these age- and sex-specific criteria in an independent second cohort (n = 77, 38 younger and 39 older adults) to evaluate age and sex differences on SW density and SW characteristics. After adapting SW amplitude criteria, we showed maintenance of an age-related difference for SW density whereas the sex-related difference vanished. Indeed, older adults produced less SW compared with younger adults. Specifically, the adapted SW amplitude criteria increased the probability of occurrence of low amplitude SW (<80 µV) for older men especially. Our results thereby confirm an age-related decline in SW generation rather than an artifact in the detection amplitude criteria. As for the SW characteristics, the age- and sex-adapted criteria display reproducible effects across the two independent cohorts suggesting a more reliable inventory of the SW

Biomarkers of dementia in obstructive sleep apnea

Epidemiologic and mechanistic evidence is increasingly supporting the notion that obstructive sleep apnea is a risk factor for dementia. Hence, the identification of patients at risk of cognitive decline due to obstructive sleep apnea may significantly improve preventive strategies and treatment decisionmaking. Cerebrospinal fluid and blood biomarkers obtained through genomic, proteomic and metabolomic approaches are improving the ability to predict incident dementia. Therefore, fluid biomarkers have the potential to predict vulnerability to neurodegeneration in individuals with obstructive sleep apnea, as well as deepen our understanding of pathophysiological processes linking obstructive sleep apnea and dementia. Many fluid biomarkers linked to Alzheimer’s disease and vascular dementia show abnormal levels in individuals with obstructive sleep apnea, suggesting that these conditions share common underlying mechanisms, including amyloid and tau protein neuropathology, inflammation, oxidative stress, and metabolic disturbances. Markers of these processes include amyloid-β, tau proteins, inflammatory cytokines, acute-phase proteins, antioxydants and oxidized products, homocysteine and clusterin (apolipoprotein J). Thus, these biomarkers may have the ability to identify adults with obstructive sleep apnea at high risk of dementia and provide an opportunity for therapeutic intervention. Large cohort studies are necessary to establish a specific fluid biomarker panel linking obstructive sleep apnea to dementia risk

A roadmap to the efficient and robust characterization of temperate terrestrial planet atmospheres with JWST

Ultra-cool dwarf stars are abundant, long-lived, and uniquely suited to enable the atmospheric study of transiting terrestrial companions with JWST. Amongst them, the most prominent is the M8.5V star TRAPPIST-1 and its seven planets, which have been the favored targets of eight JWST Cycle 1 programs. While Cycle 1 observations have started to yield preliminary insights into the planets, they have also revealed that their atmospheric exploration requires a better understanding of their host star. Here, we propose a roadmap to characterize the TRAPPIST-1 system -- and others like it -- in an efficient and robust manner. We notably recommend that -- although more challenging to schedule -- multi-transit windows be prioritized to constrain stellar heterogeneities and gather up to 2$\times$ more transits per JWST hour spent. We conclude that in such systems planets cannot be studied in isolation by small programs, thus large-scale community-supported programs should be supported to enable the efficient and robust exploration of terrestrial exoplanets in the JWST era

A roadmap for the atmospheric characterization of terrestrial exoplanets with JWST

peer reviewedUltracool dwarf stars are abundant, long-lived and uniquely suited to enable the atmospheric study of transiting terrestrial companions with the JWST. Among them, the most prominent is the M8.5V star TRAPPIST-1 and its seven planets. While JWST Cycle 1 observations have started to yield preliminary insights into the planets, they have also revealed that their atmospheric exploration requires a better understanding of their host star. Here we propose a roadmap to characterize the TRAPPIST-1 system — and others like it — in an efficient and robust manner with JWST. We notably recommend that — although more challenging to schedule — multi-transit windows be prioritized to mitigate the effects of stellar activity and gather up to twice more transits per JWST hour spent. We conclude that, for such systems, planets cannot be studied in isolation by small programmes but rather need large-scale, joint space- and ground-based initiatives to fully exploit the capabilities of JWST for the exploration of terrestrial planets

Le joual et les mutations du Québec : la question de la langue dans la définition de l'identité québécoise

Le joual, qu'il soit critiqué ou louangé, fait partie intégrante de l'identité québécoise. Contrairement à ce que l'on a prétendu pendant longtemps, les démêlés autour de la langue parlée n'ont pas commencé avec les Insolences du Frère Untel, en 1960. Déjà, en 1902, naissait la Société du parler français, qui tentait de sensibiliser les Canadiens français à l'usage du bon parler. C'est vraisemblablement à partir de là que s'est enclenché le débat sur la langue parlée au Québec. Le contexte dans lequet la ± querelle du joual¿ s'est mise en branle est important puisqu'il a contribué à forger une toute nouvelle identité chez les Canadiens français, identité qualifiée de québécoise, annonçant ainsi une volonté nette de rompre avec l'identité canadienne-française traditionnelle. Si le parler joual existe encore aujourd'hui, sous différentes formes peut-être, c'est qu'il a possiblement permis à beaucoup de Québécois de ne plus avoir honte de ce qu'ils sont et de s'exprimer à leur façon plutôt que de se taire ou d'accepter de parler une langue qui ne représente pas leur réalité. Le débat reste sensiblement le même d'hier à aujourd'hui, et les ~ommentaires et opinions sur le joual sont encore d'actualité, près d'un demi -siècle après la première sortie du , Frère Untel. TI semble que maintenant plus que jamais, s'attaquer au joual, c'est s'attaquer à l'élément le plus fondamental de l'identité québécois

Sleep slow waves’ negative-to-positive-phase transition : a marker of cognitive and apneic status in aging

The sleep slow-wave (SW) transition between negative and positive phases is thought to mirror synaptic strength and likely depends on brain health. This transition shows signifcant age-related changes but has not been investigated in pathological aging. The present study aimed at comparing the transition speed and other characteristics of SW between older adults with amnestic mild cognitive impairment (aMCI) and cognitively normal (CN) controls with and without obstructive sleep apnea (OSA). We also examined the association of SW characteristics with the longitudinal changes of episodic memory and executive functions and the degree of subjective cognitive complaints. aMCI (no/mild OSA = 17; OSA = 15) and CN (no/mild OSA = 20; OSA = 17) participants underwent a night of polysomnography and a neuropsychological evaluation at baseline and 18 months later. Participants with aMCI had a signifcantly slower SW negative-to-positive-phase transition speed and a higher proportion of SW that are “slow-switchers” than CN participants. These SW measures in the frontal region were signifcantly correlated with memory decline and cognitive complaints in aMCI and cognitive improvements in CN participants. The transition speed of the SW that are “fast-switchers” was signifcantly slower in OSA compared to no or mild obstructive sleep apnea participants. The SW transition-related metrics showed opposite correlations with the longitudinal episodic memory changes depending on the participants’ cognitive status. These relationships were particularly strong in participants with aMCI. As the changes of the SW transition-related metrics in pathological aging might refect synaptic alterations, future studies should investigate whether these new metrics covary with biomarker levels of synaptic integrity in this population

REM sleep is associated with the volume of the cholinergic basal forebrain in aMCI individuals

Abstract Background Rapid-eye movement (REM) sleep highly depends on the activity of cholinergic basal forebrain (BF) neurons and is reduced in Alzheimer’s disease. Here, we investigated the associations between the volume of BF nuclei and REM sleep characteristics, and the impact of cognitive status on these links, in late middle-aged and older participants. Methods Thirty-one cognitively healthy controls (66.8 ± 7.2 years old, 13 women) and 31 participants with amnestic Mild Cognitive Impairment (aMCI) (68.3 ± 8.8 years old, 7 women) were included in this cross-sectional study. All participants underwent polysomnography, a comprehensive neuropsychological assessment and Magnetic Resonance Imaging examination. REM sleep characteristics (i.e., percentage, latency and efficiency) were derived from polysomnographic recordings. T1-weighted images were preprocessed using CAT12 and the DARTEL algorithm, and we extracted the gray matter volume of BF regions of interest using a probabilistic atlas implemented in the JuBrain Anatomy Toolbox. Multiple linear regressions were performed between the volume of BF nuclei and REM sleep characteristics controlling for age, sex and total intracranial volume, in the whole cohort and in subgroups stratified by cognitive status. Results In the whole sample, lower REM sleep percentage was significantly associated to lower nucleus basalis of Meynert (Ch4) volume (β = 0.32, p = 0.009). When stratifying the cohort according to cognitive status, lower REM sleep percentage was significantly associated to both lower Ch4 (β = 0.48, p = 0.012) and total BF volumes (β = 0.44, p = 0.014) in aMCI individuals, but not in cognitively unimpaired participants. No significant associations were observed between the volume of the BF and wake after sleep onset or non-REM sleep variables. Discussion These results suggest that REM sleep disturbances may be an early manifestation of the degeneration of the BF cholinergic system before the onset of dementia, especially in participants with mild memory deficits

High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies

Developmental and epileptic encephalopathy (DEE) is a group of conditions characterized by the co-occurrence of epilepsy and intellectual disability (ID), typically with developmental plateauing or regression associated with frequent epileptiform activity. The cause of DEE remains unknown in the majority of cases. We performed whole-genome sequencing (WGS) in 197 individuals with unexplained DEE and pharmaco-resistant seizures and in their unaffected parents. We focused our attention on de novo mutations (DNMs) and identified candidate genes containing such variants. We sought to identify additional subjects with DNMs in these genes by performing targeted sequencing in another series of individuals with DEE and by mining various sequencing datasets. We also performed meta-analyses to document enrichment of DNMs in candidate genes by leveraging our WGS dataset with those of several DEE and ID series. By combining these strategies, we were able to provide a causal link between DEE and the following genes: NTRK2, GABRB2, CLTC, DHDDS, NUS1, RAB11A, GABBR2, and SNAP25. Overall, we established a molecular diagnosis in 63/197 (32%) individuals in our WGS series. The main cause of DEE in these individuals was de novo point mutations (53/63 solved cases), followed by inherited mutations (6/63 solved cases) and de novo CNVs (4/63 solved cases). De novo missense variants explained a larger proportion of individuals in our series than in other series that were primarily ascertained because of ID. Moreover, these DNMs were more frequently recurrent than those identified in ID series. These observations indicate that the genetic landscape of DEE might be different from that of ID without epilepsy