Additive and Specific Effects of Elicitor Treatments on the Metabolic Profile of Arabidopsis thaliana.

Several elicitors of plant defense have been identified and numerous efforts to use them in the field have been made. Exogenous elicitor treatments mimic the in planta activation of pattern-triggered immunity (PTI), which relies on the perception of pathogen-associated molecular patterns (PAMPs) such as bacterial flg22 or fungal chitins. Early transcriptional responses to distinct PAMPs are mostly overlapping, regardless of the elicitor being used. However, it remains poorly known if the same patterns are observed for metabolites and proteins produced later during PTI. In addition, little is known about the impact of a combination of elicitors on PTI and the level of induced resistance to pathogens. Here, we monitored Arabidopsis thaliana resistance to the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 (Pto DC3000) following application of flg22 and chitosan elicitors, used individually or in combination. A slight, but not statistically significant increase in induced resistance was observed when the elicitors were applied together when compared with individual treatments. We investigated the effect of these treatments on the metabolome by using an untargeted analysis. We found that the combination of flg22 and chitosan impacted a higher number of metabolites and deregulated specific metabolic pathways compared with the elicitors individually. These results contribute to a better understanding of plant responses to elicitors, which might help better rationalize their use in the field. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

A Self-Help Virtual Therapeutic Experience Intervention for Overcoming Psychological Distress Related to the COVID-19 Pandemic: Results From the European Multicentric COVID Feel Good Trial.

OBJECTIVE: The general objective of the current study was to investigate the efficacy of a novel self-help virtual therapeutic experience (specifically, the COVID Feel Good intervention) in lowering the psychological burden experienced during the COVID-19 lockdowns in four European countries. METHODS: We focused on participants recruited from June 2020 to May 2021 in the context of a European multicenter project including four university/academic sites. The total number of participants in the longitudinal studies was 107 (study 1, N = 40; study 2, N = 29; study 3, N = 38). The randomized controlled trial (study 4) included 31 participants in total, 16 in the intervention group and 15 in the control group. Primary outcome measures were depression, anxiety, stress symptoms, perceived stress level, and perceived hopelessness. The secondary outcome was experienced social connectedness. RESULTS: Using separate linear mixed-effects models, the most consistent result across countries was a reduction in perceived stress after the participation in the COVID Feel Good intervention. By pooling the results of the models using a random-effects meta-analysis, we found that after the COVID Feel Good intervention, participants reported a decrease in perceived general distress (mean standardized effect size for general distress in the treatment groups compared with the control conditions was -0.52 [ p = .008, 95% confidence interval = -0.89 to -0.14]) and an increase in the perceived social connection (mean standardized effect size for social connection using COVID Feel Good compared with the control conditions was 0.50 [ p ≤ .001, 95% confidence interval = 0.25 to 0.76]). CONCLUSIONS: Findings of this study indicate that a virtual self-help intervention is effective in reducing psychological distress. These results contribute to the growing literature supporting the use of digital psychological therapies to relieve psychological distress among the general population during the COVID-19 pandemic.Trial Registration : ISRCTN63887521.

Feasibility of advanced composite endpoint analysis: Post-hoc insights from the vitamin intervention for stroke prevention randomized control trial.

BACKGROUND AND AIMS: Stroke is a major cause of mortality and disability, highlighting the importance of prevention. Clinical trials play an important role in evaluating interventions that can maximize stroke prevention. Traditional composite endpoints (TCE) used in clinical trials have limitations, as they pool together events of varying clinical importance. Weighted composite endpoints (WCE) have emerged as a solution to address these limitations and provide more accurate assessments of outcomes. In this study, we investigate the use of WCE in a previously reported negative clinical trial for stroke prevention. METHODS AND RESULTS: We analyzed data from the Vitamin Intervention for Stroke Prevention (VISP) trial, which compared high dose and low dose multivitamin therapy. We utilized weighted methods to analyze time-to-event outcomes with censoring. The primary outcomes of interest were time to nonfatal stroke, nonfatal coronary events, and death. We calculated modified Kaplan-Meier (KM) curves for each intervention group. We also performed a modified log-rank test to assess significant differences based on the weighted KM curves. The analysis included 3668 VISP trial participants, and most remained event-free throughout the study period. The TCE KM curve showed no significant difference in outcomes between high dose and low dose groups. Similarly, the WCE KM curves, with different weights assigned to each outcome, did not reveal significant differences in outcomes between the studied groups. CONCLUSION: This post-hoc analysis confirms the negative trial results of VISP and demonstrates the feasibility of using WCE in assessing nutrition-based interventions for stroke prevention.

Arterial Preparation by Longitudinal Micro-Incisions Before Balloon Angioplasty of the Superficial Femoral and Popliteal Artery: Acute and 12-Month Results.

PURPOSE: Percutaneous transluminal angioplasty (PTA) with conventional plain old balloon (POBA) and/or drug-coated balloon (DCB) is the primary intervention to treat peripheral artery stenoses. However, acute dissections during the procedure and potential for future target lesion revascularization remain procedural complications. The purpose of this study was to assess the acute and 12-month outcomes in patients who underwent novel vessel preparation with longitudinal, controlled-depth micro-incisions prior to PTA. MATERIALS AND METHODS: Patients with symptomatic lower extremity peripheral arterial disease with a Rutherford class of 2 to 6 and >70% de novo stenosis of the superficial femoral or popliteal arteries were included in this retrospective study. Patients with thrombotic or embolic lesions, restenosis, or in-stent restenosis were excluded. The FLEX Vessel Prep System (FLEX VP) was used to prepare the vessel prior to PTA by creating micro-incisions at the target lesion. The FLEX VP was followed by POBA or paclitaxel DCB. RESULTS: The study included 65 patients. Lesion characteristics were 90% median stenosis (range = 70%-100%), 75.4% mild-to-severe calcifications, and 33.8% occlusion rate, and median lesion length was 196 (range = 10-480) mm. Following vessel preparation, 82.1% of the patients had low severity dissection or no flow-limiting dissection. The provisional stent rate postprocedure was 16.9%, with a median stent length of 60 mm. The freedom from target lesion revascularization (FFTLR) in 63 evaluable patients at 6 and 12 months was 98.4% and 93.7%, respectively. Freedom from amputation was 100%. CONCLUSION: In this real-world/all-comers patient population with long, stenotic lesions across the calcification spectrum, vessel preparation with longitudinal micro-incisions prior to PTA was associated with low dissection rate, low dissection severity, low stent implantation, and high FFTLR with the absence of amputation at 12 months relative to published reports in long-lesion cohorts. These results support vessel preparation via micro-incisions.

Simplified therapeutic guidelines: the main tool of antimicrobial stewardship programs associated with optimal antibiotic therapy.

Hospitals regularly seek to upgrade their antimicrobial stewardship program (ASP). Our aim was to evaluate the impact of simplified therapeutic guidelines (STGs) compared to various established tools for ASP on the rate of optimal antibiotic therapy (OAT) and antibiotic consumption. Audits of antibiotic prescriptions were carried out over a 24-month period. Feedback information led to STGs (e.g., ≤ 15 drugs). The impact of STGs was based on the rate of OAT, defined as a diagnosis of the infectious disease in the patient's medical records associated with the corresponding therapy indicated in the STGs or in other guidelines. STGs were compared to five other means of ASP: internal or national guidelines, audit, information regarding antibiotic consumption and bacterial resistance, and restricted access to targeted antibiotics. Antibiotic consumption was measured in defined daily doses/1000 days of hospital stay, focusing on third-generation cephalosporins (TGC) and fluoroquinolones (FQ). Twenty-six hospitals were audited from April 2017 to June 2019. A total of 1,028 antibiotic prescriptions were analyzed, including 204 (20%) after STG implementation in seven hospitals. In multivariate analysis, OAT (n = 176, 17%) was associated with STGs, AOR 2.21 [1.51-3.22], and with three tools in place, 1.75 [1.24-2.48]. The relative variations of consumption of TGC and FQ for hospitals with or without STGs were - 13.1 vs. + 9.4% and - 18.5 vs. - 2.7%, respectively, from 2018 to 2019. STGs were more likely than other ASP tools to improve the rate of OAT and to reduce the consumption of antibiotics.

[The care pathway coordination nurse, an emerging profession]. / L'infirmier de coordination de parcours de soins, un métier émergent.

The care pathway coordination nurse acts in close collaboration with the various professionals in the health, social and medico-social fields to improve the patient's pathway. His or her coordination of the care pathway, over a given period of time, promotes personalized support within the framework of structured care that also considers the patient's health and life paths.

Brain 5-HT1A Receptor Binding in Multiple System Atrophy: An [18 F]-MPPF PET Study.

BACKGROUND: Loss of medullary serotonin (5-hydroxytryptamine) neurons has been linked to respiratory disturbances in multiple system atrophy (MSA). Broader 5-hydroxytryptamine dysfunction may contribute to additional motor/nonmotor symptoms in MSA. The objective of this study was to compare brain 5-hydroxytryptamine1A receptor binding between MSA and healthy controls. Secondary objectives were to compare 5-hydroxytryptamine1A receptor binding between MSA and Parkinson's disease (PD) and to assess potential associations with motor/nonmotor symptoms in MSA. METHODS: 2'-Methoxyphenyl-(N-2'-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine positron emission tomography was performed in matched MSA patients (n = 16), PD patients (n = 15), and healthy controls (n = 18). RESULTS: 2'-Methoxyphenyl-(N-2'-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine distribution volume ratios were lower in MSA patients versus healthy controls in several brain regions including the caudate, raphe nuclei, thalamus, and brain stem. Distribution volume ratios were also lower in brain stem and amygdala in MSA versus PD. Moderate associations were found between 2'-methoxyphenyl-(N-2'-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine distribution volume ratios and fatigue, pain, and apathy in MSA. CONCLUSION: Our results demonstrate 5-hydroxytryptamine dysfunction in several brain regions in MSA, which may contribute to fatigue, pain, and apathy. © 2020 International Parkinson and Movement Disorder Society.

Clinical experience and categorical perception of children's speech.

BACKGROUND: Accurate and detailed records of children's speech are a critical component of competent service delivery in speech-language pathology/speech and language therapy (SLP/SLT). Previous research has shown that during speech-sound acquisition, children gradually learn to produce sounds in adult-like manners. Continuous rating scales are a way to track this gradual learning. AIMS: To examine whether clinical experience affects the ability and willingness to rate children's speech production using continuous rating scales. METHODS & PROCEDURES: An online survey was administered to 81 US-based SLPs/SLTs, binned into more- and less-experienced groups, and 20 non-SLPs/SLTs. The survey included a speech-sound rating task in which participants rated the production of place of articulation in children's productions of word-initial /θ/, /s/, /ʃ/, /d/, /ɡ/, /t/ and /k/ on a nine-point equally appearing interval scale. We examined the extent to which these were accurate (i.e., the extent to which they matched laboratory measures of production characteristics) and the extent to which the ratings were gradual (i.e., they used the entire rating scales, rather than just the endpoints). MAIN CONTRIBUTION: There were no consistent differences between non-SLPs/SLTs, less-experienced SLPs/SLTs and more-experienced SLPs/SLTs in a measure of the accuracy of responses. More consistent differences were found in the extent to which listeners used the endpoints of the scale: greater experience was associated with greater use of the endpoint values. CONCLUSIONS & IMPLICATIONS: More-experienced SLPs/SLTs are less likely to use the entire range of continuous rating scales to rate children's speech accuracy than less-experienced SLPs/SLTs or clinically untrained listeners. Implications for service delivery are discussed. What this paper adds What is already known on the subject Children's productions of individual sounds, like /k/, become gradually more adult-like over the course of development. For a child who has a [t] for /k/ error, this gradual development means that children's productions become progressively less like /t/ and more like /k/ over development. Phonetic transcription does not capture this gradual development. In contrast, studies have shown that continuous ratings of children's speech (such as rating productions on a scale anchored by the text "the 't' sound" at one end and "the 'k' sound" at the other end) can capture this gradual development. What this paper adds to existing knowledge To determine continuous ratings are clinically feasible, we must first determine whether clinical experience affects people's use of continuous rating scales to rate children's speech. We conducted an on-line speech perception experiment in which 81 speech-language pathologists/speech and language therapists (SLPs/SLTs) and 20 non-SLPs/SLTs rated 60 productions by children on continuous rating scales. The 60 stimuli included many sounds that had been independently verified to be intermediate productions (i.e., a target /k/ that was neither completely /k/-like nor completely /t/-like). Non-SLPs/SLTs and less-experienced SLPs/SLTs rated those intermediate sounds with intermediate ratings (i.e., somewhere on the midpoint of a continuous scale). In contrast, more-experienced SLPs/SLTs were more likely to rate those sounds as instances of endpoints (i.e., as either /k/ or /t/). What are the potential or actual clinical implications of this work? This finding suggests that clinical experience is paradoxically associated with a reduced tendency to use the entire range of responses on continuous rating scales. This finding suggests that we must better understand the cause of this reduced tendency, so that clinicians at all levels can use continuous rating scales equally effectively.

Pre-treatment magnetic resonance-based texture features as potential imaging biomarkers for predicting event free survival in anal cancer treated by chemoradiotherapy.

AIM: To assess regular MRI findings and tumour texture features on pre-CRT imaging as potential predictive factors of event-free survival (disease progression or death) after chemoradiotherapy (CRT) for anal squamous cell carcinoma (ASCC) without metastasis. MATERIALS AND METHODS: We retrospectively included 28 patients treated by CRT for pathologically proven ASCC with a pre-CRT MRI. Texture analysis was carried out with axial T2W images by delineating a 3D region of interest around the entire tumour volume. First-order analysis by quantification of the histogram was carried out. Second-order statistical texture features were derived from the calculation of the grey-level co-occurrence matrix using a distance of 1 (d1), 2 (d2) and 5 (d5) pixels. Prognostic factors were assessed by Cox regression and performance of the model by the Harrell C-index. RESULTS: Eight tumour progressions led to six tumour-specific deaths. After adjusting for age, gender and tumour grade, skewness (HR = 0.131, 95% CI = 0-0.447, p = 0.005) and cluster shade_d1 (HR = 0.601, 95% CI = 0-0.861, p = 0.027) were associated with event occurrence. The corresponding Harrell C-indices were 0.846, 95% CI = 0.697-0.993, and 0.851, 95% CI = 0.708-0.994. CONCLUSION: ASCC MR texture analysis provides prognostic factors of event occurrence and requires additional studies to assess its potential in an "individual dose" strategy for ASCC chemoradiation therapy. KEY POINTS: • MR texture features help to identify tumours with high progression risk. • Texture feature maps help to identify intra-tumoral heterogeneity. • Texture features are a better prognostic factor than regular MR findings.

PECTIN METHYLESTERASE48 is involved in Arabidopsis pollen grain germination.

Germination of pollen grains is a crucial step in plant reproduction. However, the molecular mechanisms involved remain unclear. We investigated the role of PECTIN METHYLESTERASE48 (PME48), an enzyme implicated in the remodeling of pectins in Arabidopsis (Arabidopsis thaliana) pollen. A combination of functional genomics, gene expression, in vivo and in vitro pollen germination, immunolabeling, and biochemical analyses was used on wild-type and Atpme48 mutant plants. We showed that AtPME48 is specifically expressed in the male gametophyte and is the second most expressed PME in dry and imbibed pollen grains. Pollen grains from homozygous mutant lines displayed a significant delay in imbibition and germination in vitro and in vivo. Moreover, numerous pollen grains showed two tips emerging instead of one in the wild type. Immunolabeling and Fourier transform infrared analyses showed that the degree of methylesterification of the homogalacturonan was higher in pme48-/- pollen grains. In contrast, the PME activity was lower in pme48-/-, partly due to a reduction of PME48 activity revealed by zymogram. Interestingly, the wild-type phenotype was restored in pme48-/- with the optimum germination medium supplemented with 2.5 mm calcium chloride, suggesting that in the wild-type pollen, the weakly methylesterified homogalacturonan is a source of Ca(2+) necessary for pollen germination. Although pollen-specific PMEs are traditionally associated with pollen tube elongation, this study provides strong evidence that PME48 impacts the mechanical properties of the intine wall during maturation of the pollen grain, which, in turn, influences pollen grain germination.

Three-Dimensional Measurement of Hepatocellular Carcinoma Ablation Zones and Margins for Predicting Local Tumor Progression.

PURPOSE: To propose a postprocessing technique that measures tumor surface with insufficient ablative margins (≤ 5 mm) on magnetic resonance (MR) imaging to predict local tumor progression (LTP) following radiofrequency (RF) ablation. MATERIALS AND METHODS: A diagnostic method is proposed based on measurement of tumor surface with a margin ≤ 5 mm on MR imaging. The postprocessing technique includes fully automatic registration of pre- and post-RF ablation MR imaging, a semiautomatic segmentation of pre-RF ablation tumor and post-RF ablation volume, and a subsequent calculation of the three-dimensional exposed tumor surface area. The ability to use this surface margin ≤ 5 mm to predict local recurrence at 2 years was then tested on 16 patients with cirrhosis who were treated by RF ablation with a margin ≤ 5 mm in 2012: eight with LTP matched according to tumor size and number and α-fetoprotein level versus eight without local recurrence. RESULTS: The error of estimated tumor surface with a margin ≤ 5 mm was less than 12%. Results of a log-rank test showed that patients with a tumor surface area > 425 mm(2) had a 2-year LTP rate of 77.5%, compared with 25% for patients with a tumor surface area ≤ 425 mm(2) (P = .018). CONCLUSIONS: This proof-of-concept study proposes an accurate and reliable postprocessing technique to estimate tumor surface with insufficient ablative margins, and underscores the potential usefulness of tumor surface with a margin ≤ 5 mm to stratify patients with HCC treated by RF ablation according to their risk of LTP.

Exploring the N-glycosylation pathway in Chlamydomonas reinhardtii unravels novel complex structures.

Chlamydomonas reinhardtii is a green unicellular eukaryotic model organism for studying relevant biological and biotechnological questions. The availability of genomic resources and the growing interest in C. reinhardtii as an emerging cell factory for the industrial production of biopharmaceuticals require an in-depth analysis of protein N-glycosylation in this organism. Accordingly, we used a comprehensive approach including genomic, glycomic, and glycoproteomic techniques to unravel the N-glycosylation pathway of C. reinhardtii. Using mass-spectrometry-based approaches, we found that both endogenous soluble and membrane-bound proteins carry predominantly oligomannosides ranging from Man-2 to Man-5. In addition, minor complex N-linked glycans were identified as being composed of partially 6-O-methylated Man-3 to Man-5 carrying one or two xylose residues. These findings were supported by results from a glycoproteomic approach that led to the identification of 86 glycoproteins. Here, a combination of in-source collision-induced dissodiation (CID) for glycan fragmentation followed by mass tag-triggered CID for peptide sequencing and PNGase F treatment of glycopeptides in the presence of (18)O-labeled water in conjunction with CID mass spectrometric analyses were employed. In conclusion, our data support the notion that the biosynthesis and maturation of N-linked glycans in the endoplasmic reticulum and Golgi apparatus occur via a GnT I-independent pathway yielding novel complex N-linked glycans that maturate differently from their counterparts in land plants.

Deciphering the responses of root border-like cells of Arabidopsis and flax to pathogen-derived elicitors.

Plant pathogens including fungi and bacteria cause many of the most serious crop diseases. The plant innate immune response is triggered upon recognition of microbe-associated molecular patterns (MAMPs) such as flagellin22 and peptidoglycan. To date, very little is known of MAMP-mediated responses in roots. Root border cells are cells that originate from root caps and are released individually into the rhizosphere. Root tips of Arabidopsis (Arabidopsis thaliana) and flax (Linum usitatissimum) release cells known as "border-like cells." Whereas root border cells of pea (Pisum sativum) are clearly involved in defense against fungal pathogens, the function of border-like cells remains to be established. In this study, we have investigated the responses of root border-like cells of Arabidopsis and flax to flagellin22 and peptidoglycan. We found that both MAMPs triggered a rapid oxidative burst in root border-like cells of both species. The production of reactive oxygen species was accompanied by modifications in the cell wall distribution of extensin epitopes. Extensins are hydroxyproline-rich glycoproteins that can be cross linked by hydrogen peroxide to enhance the mechanical strength of the cell wall. In addition, both MAMPs also caused deposition of callose, a well-known marker of MAMP-elicited defense. Furthermore, flagellin22 induced the overexpression of genes involved in the plant immune response in root border-like cells of Arabidopsis. Our findings demonstrate that root border-like cells of flax and Arabidopsis are able to perceive an elicitation and activate defense responses. We also show that cell wall extensin is involved in the innate immunity response of root border-like cells.

The cell wall pectic polymer rhamnogalacturonan-II is required for proper pollen tube elongation: implications of a putative sialyltransferase-like protein.

BACKGROUND AND AIMS: Rhamnogalacturonan-II (RG-II) is one of the pectin motifs found in the cell wall of all land plants. It contains sugars such as 2-keto-3-deoxy-d-lyxo-heptulosaric acid (Dha) and 2-keto-3-deoxy-d-manno-octulosonic acid (Kdo), and within the wall RG-II is mostly found as a dimer via a borate diester cross-link. To date, little is known regarding the biosynthesis of this motif. Here, after a brief review of our current knowledge on RG-II structure, biosynthesis and function in plants, this study explores the implications of the presence of a Golgi-localized sialyltransferase-like 2 (SIA2) protein that is possibly involved in the transfer of Dha or Kdo in the RG-II of Arabidopsis thaliana pollen tubes, a fast-growing cell type used as a model for the study of cell elongation. METHODS: Two heterozygous mutant lines of arabidopsis (sia2-1+/- and qrt1 × sia2-2+/-) were investigated. sia2-2+/- was in a quartet1 background and the inserted T-DNA contained the reporter gene ß-glucuronidase (GUS) under the pollen-specific promoter LAT52. Pollen germination and pollen tube phenotype and growth were analysed both in vitro and in vivo by microscopy. KEY RESULTS: Self-pollination of heterozygous lines produced no homozygous plants in the progeny, which may suggest that the mutation could be lethal. Heterozygous mutants displayed a much lower germination rate overall and exhibited a substantial delay in germination (20 h of delay to reach 30 % of pollen grain germination compared with the wild type). In both lines, mutant pollen grains that were able to produce a tube had tubes that were either bursting, abnormal (swollen or dichotomous branching tip) or much shorter compared with wild-type pollen tubes. In vivo, mutant pollen tubes were restricted to the style, whereas the wild-type pollen tubes were detected at the base of the ovary. CONCLUSIONS: This study highlights that the mutation in arabidopsis SIA2 encoding a sialyltransferase-like protein that may transfer Dha or Kdo on the RG-II motif has a dramatic effect on the stability of the pollen tube cell wall.

[Consultations with a nurse specialized in cognitive behavioural therapies]. / Une consultation infirmière spécialisée en therapies comportementales et cognitives.

Cognitive behavioural therapies (CBT), which have been proven to be effective, are tools which are simple to use and implement. In Sainte Anne hospital, consultations with a nurse specialised in CBT were first set up in 2011.The nurse specialised in CBT sees the patients on a one-to-one basis and often plays, within the multidisciplinary team, the role of care coordinator.

BacA: a possible regulator that contributes to the biofilm formation of Pseudomonas aeruginosa.

Previously, we pointed out in P. aeruginosa PAO1 biofilm cells the accumulation of a hypothetical protein named PA3731 and showed that the deletion of the corresponding gene impacted its biofilm formation capacity. PA3731 belongs to a cluster of 4 genes (pa3732 to pa3729) that we named bac for "Biofilm Associated Cluster." The present study focuses on the PA14_16140 protein, i.e., the PA3732 (BacA) homolog in the PA14 strain. The role of BacA in rhamnolipid secretion, biofilm formation and virulence, was confirmed by phenotypic experiments with a bacA mutant. Additional investigations allow to advance that the bac system involves in fact 6 genes organized in operon, i.e., bacA to bacF. At a molecular level, quantitative proteomic studies revealed an accumulation of the BAC cognate partners by the bacA sessile mutant, suggesting a negative control of BacA toward the bac operon. Finally, a first crystallographic structure of BacA was obtained revealing a structure homologous to chaperones or/and regulatory proteins.

[Advanced Practice and Digital Health]. / Pratique avancée et santé numérique.

Digital health has become indispensable and inseparable from the current healthcare system. However, it is still often presented as a mysterious world that needs to be tamed in order to participate in innovations from their conception and to best accompany patients towards improving the quality and safety of care.

Night-to-night variability in sleep and amyloid beta burden in normal aging.

INTRODUCTION: Alzheimer's disease is associated with sleep disturbances and accumulation of cerebral amyloid beta. The objective was to examine whether actigraphy-detected sleep parameters might be biomarkers for early amyloid burden. METHODS: Participants underwent a week of actigraphy and an amyloid positron emission tomography (PET) scan. Sleep duration and continuity disruption (sleep fragmentation and nocturnal awakenings) were extracted and compared between amyloid-positive and amyloid-negative participants. Then multiple linear regressions were used between mean or night-to-night intra-individual variability (standard deviation) of sleep parameters and brain amyloid burden in a voxel-wise analysis. RESULTS: Eighty-six subjects were included (80.3 ± 5.4 years; 48.8% of women). Amyloid-positive participants had a higher variability of sleep fragmentation compared to amyloid-negative participants. This parameter was associated with a higher amyloid burden in the frontal and parietal regions, and in the precuneus, in the whole sample. DISCUSSION: This study highlights the relevance of using variability in sleep continuity as a potential biomarker of early amyloid pathogenesis.