Neural correlates of impaired cognitive processes underlying self-unawareness in Alzheimer's disease.

Self-unawareness concerning current symptoms remains a clinical challenge in Alzheimer's disease. Reduced self-awareness likely depends on complex biopsychosocial mechanisms that comprise multiple cognitive processes, regulated by personal goals and values. We specifically reviewed the cognitive processes impaired in unaware participants with AD by emphasizing the related impaired brain activity observed during task-based fMRI. Unawareness can be explained by a failure in functioning of or in connection between brain regions that intervene in access, retrieval and updating of (present or extended) self-information (posterior midline, medial temporal, inferior parietal cortices), or in its monitoring, evaluation, or control (medial and lateral prefrontal cortices). Although one must be cautious when relating function to brain regions, impaired processes were tentatively related to the Cognitive Awareness Model. Although brain function depends on neural networks, impaired brain activity during cognitive processes was discussed according to previous studies reporting correlations between brain regions and scores of anosognosia. The review provides a framework to help clinicians considering processes that can explain unawareness in dementia. In patients at early stages of AD, different levels of awareness of cognitive or social clinical changes might be described as impairment in the interaction between specific cognitive processes and contents.

Efficacy and safety of the TENSI+ device for posterior tibial nerve stimulation: A multicenter, retrospective study.

OBJECTIVES: Transcutaneous posterior tibial nerve stimulation (TC-PTNS) is a validated option for lower urinary tract symptoms (LUTS) management, with a short-term success rate of around 60% and few adverse events. Our goal was to report the efficacy and safety results of TC-PTNS using the newly issued device TENSI+ for LUTS management. PATIENTS AND METHODS: A multicenter, retrospective study was conducted in 7 urology departments in France. All patients treated with TC-PTNS for LUTS using the TENSI+ device between September 2021 and February 2022 were included. All patients received supervised at-home training by a specialized nurse. All patients were asked to do daily, 20minutes sessions of TC-PTNS. Patient demographics, history, initial symptoms and previous treatment were collected at inclusion. A follow-up visit was scheduled at 3 months. Efficacy was evaluated through treatment persistence at 3 months and PGI-I (Patient Global Impression of Improvement) score. Adverse events were recorded. RESULTS: One hundred and three patients (86 women and 17 men) were included. All patients had overactive bladder symptoms, 64 suffered from urgency incontinence, and 24 had associated voiding symptoms. Eighteen patients had neurogenic background, and 30 previously received anticholinergics. After a median follow-up of 12 [10-21]weeks, 70 patients were still using the device (68%). PGI-I score reflected an improvement in 70.9% and was 1, 2 and 3 in 28, 26 and 19 patients respectively, while 24 were unchanged and 6 were worse. No clinical baseline parameter was predictive of success. Adverse events included pain at stimulation site (two cases) and pelvic pain (two patients), which rapidly resolved after treatment interruption. CONCLUSIONS: TC-PTNS with TENSI+ device is an effective option for LUTS management, with results that seem similar to other TC-PTNS approaches. Adverse events were mild and reversible after treatment interruption.

[Multidisciplinary meetings in pelvic floor disease in women: A national survey by the CUROPF among French urologists]. / Réunion de concertation pluridisciplinaire en pelvipérinéologie en France : résultats d'une enquête nationale du CUROPF auprès des urologues français.

INTRODUCTION: Multidisciplinary team meetings (MTMs) in the field of pelvic floor diseases in women tend to generalize, as they are required as mandatory before mid-urethral sling implantation or sacrocolpopexy by recent decrees published by the French health authorities. However, access to these meetings is variable in the French territory. The goal of the present study was to describe the existence and the settings of these kinds of meetings in France. MATERIEL AND METHODS: An on-line survey was conducted between June and July 2020 (stage 1) then between November 2021 and January 2022 (stage 2). A 15-item questionnaire was sent to all members of the Association française d'urologie (AFU). A descriptive analysis was conducted. RESULTS: Three hundred and twenty-two completed questionnaires were sent back during stage 1 and 158 during stage 2. Early 2022, 61.3% of respondents had access to a pelviperineology MTM, with important difference according to geographical areas. Main activity of MTMs was case discussion of complex situations (68% of meetings). At the end of 2021, 22% of the respondents declared willing to stop partially or totally their pelviperineology activity, given the new regulations set in place by the authorities. CONCLUSION: Despite being absolutely mandatory in current clinical practice, MTMs in pelvic floor disease have spread slowly. MTMs implementation was still insufficient in 2022, and variable on the French territory. Some urologists declare having no access to such resources and about 1 out of 5 were considering to voluntary stop of decrease significantly their activity in this difficult context.

A method to identify the weakest link in urban drainage systems.

Urban drainage systems are composed of subsystems. The ratio of the storage and discharge capacities of the subsystems determines the performance. The performance of the urban water system may deteriorate as a result of the change in the ratio of storage to discharge capacity due to aging, urbanisation and climate change. We developed the graph-based weakest link method (GBWLM) to analyse urban drainage systems. Flow path analysis from graph theory is applied instead of hydrodynamic model simulations to reduce the computational effort. This makes it practically feasible to analyse urban drainage systems with multi-decade rainfall series. We used the GBWLM to analyse the effect of urban water system aging and/or climate scenarios on flood extent and frequency. The case study shows that the results of the hydrodynamic models and the GBWLM are similar. The rainfall intensities of storm events are expected to increase by approximately 20% in the Netherlands due to climate change. For the case study, such an increase in load has little impact on the flood frequency and extent caused by gully pots and surface water. However, it could lead to a 50% increase in the storm sewer flood frequency and an increase in the extent of flooding.

Preclinical assessment of antigen-specific chimeric antigen receptor regulatory T cells for use in solid organ transplantation.

A primary goal in transplantation medicine is the induction of a tolerogenic environment for prevention of transplant rejection without the need for long-term pharmacological immunosuppression. Generation of alloantigen-specific regulatory T cells (Tregs) by transduction with chimeric antigen receptors (CARs) is a promising strategy to achieve this goal. This publication reports the preclinical characterization of Tregs (TR101) transduced with a human leukocyte antigen (HLA)-A*02 CAR lentiviral vector (TX200) designated to induce immunosuppression of allograft-specific effector T cells in HLA-A*02-negative recipients of HLA-A*02-positive transplants. In vitro results demonstrated specificity, immunosuppressive function, and safety of TX200-TR101. In NOD scid gamma (NSG) mice, TX200-TR101 prevented graft-versus-host disease (GvHD) in a xenogeneic GvHD model and TX200-TR101 Tregs localized to human HLA-A*02-positive skin transplants in a transplant model. TX200-TR101 persisted over the entire duration of a 3-month study in humanized HLA-A*02 NSG mice and remained stable, without switching to a proinflammatory phenotype. Concomitant tacrolimus did not impair TX200-TR101 Treg survival or their ability to inhibit peripheral blood mononuclear cell (PBMC) engraftment. These data demonstrate that TX200-TR101 is specific, stable, efficacious, and safe in preclinical models, and provide the basis for a first-in-human study.

Identifying brain network topology changes in task processes and psychiatric disorders.

A central goal in neuroscience is to understand how dynamic networks of neural activity produce effective representations of the world. Advances in the theory of graph measures raise the possibility of elucidating network topologies central to the construction of these representations. We leverage a result from the description of lollipop graphs to identify an iconic network topology in functional magnetic resonance imaging data and characterize changes to those networks during task performance and in populations diagnosed with psychiatric disorders. During task performance, we find that task-relevant subnetworks change topology, becoming more integrated by increasing connectivity throughout cortex. Analysis of resting state connectivity in clinical populations shows a similar pattern of subnetwork topology changes; resting scans becoming less default-like with more integrated sensory paths. The study of brain network topologies and their relationship to cognitive models of information processing raises new opportunities for understanding brain function and its disorders.

Metrics for graph comparison: A practitioner's guide.

Comparison of graph structure is a ubiquitous task in data analysis and machine learning, with diverse applications in fields such as neuroscience, cyber security, social network analysis, and bioinformatics, among others. Discovery and comparison of structures such as modular communities, rich clubs, hubs, and trees yield insight into the generative mechanisms and functional properties of the graph. Often, two graphs are compared via a pairwise distance measure, with a small distance indicating structural similarity and vice versa. Common choices include spectral distances and distances based on node affinities. However, there has of yet been no comparative study of the efficacy of these distance measures in discerning between common graph topologies at different structural scales. In this work, we compare commonly used graph metrics and distance measures, and demonstrate their ability to discern between common topological features found in both random graph models and real world networks. We put forward a multi-scale picture of graph structure wherein we study the effect of global and local structures on changes in distance measures. We make recommendations on the applicability of different distance measures to the analysis of empirical graph data based on this multi-scale view. Finally, we introduce the Python library NetComp that implements the graph distances used in this work.

In vivo imaging of synaptic loss in Alzheimer's disease with [18F]UCB-H positron emission tomography.

PURPOSE: Loss of brain synapses is an early pathological feature of Alzheimer's disease. The current study assessed synaptic loss in vivo with positron emission tomography and an 18F-labelled radiotracer of the synaptic vesicle protein 2A, [18F]UCB-H. METHODS: Twenty-four patients with mild cognitive impairment or Alzheimer's disease and positive [18F]Flutemetamol amyloid-PET were compared to 19 healthy controls. [18F]UCB-H brain uptake was quantified with Logan graphical analysis using an image-derived blood input function. SPM12 and regions-of-interest (ROI) analyses were used for group comparisons of regional brain distribution volumes and for correlation with cognitive measures. RESULTS: A significant decrease of [18F]UCB-H uptake was observed in several cortical areas (11 to 18% difference) and in the thalamus (16% difference), with the largest effect size in the hippocampus (31% difference). Reduced hippocampal uptake was related to patients' cognitive decline (ROI analysis) and unawareness of memory problems (SPM and ROI analyses). CONCLUSIONS: The findings thus highlight predominant synaptic loss in the hippocampus, confirming previous autopsy-based studies and a recent PET study with an 11C-labelled SV2A radiotracer. [18F]UCB-H PET allows to image in vivo synaptic changes in Alzheimer's disease and to relate them to patients' cognitive impairment.

[Surgical management of genital prolapse]. / Prise en charge chirurgicale des prolapsus génitaux.

Although non invasive options exist, surgical management of genital prolapse is a gold standard. The main surgical approaches are abdominal -sacrocolpopexy- and vaginal -with or without mesh-. Sacrocolpopexy has proven to have better results than vaginal techniques, but is not appropriate for all women. Vaginal surgery remains a good option especially in older women who no longer have sexual activity. The surgical approach must adapt to patients' clinical characteristics. The choice has to be a shared decision after patients' loyal information.

PRISE EN CHARGE CHIRURGICALE DES PROLAPSUS GÉNITAUX Bien qu'il existe des options non invasives de prise en charge des prolapsus, leur traitement de référence est chirurgical. Il existe deux voies d'abord principales : la voie abdominale -promontofixation- et la voie vaginale -sans ou avec pose de prothèse-. La promontofixation a montré sa supériorité sur les techniques vaginales, mais ne peut être appliquée à toutes les femmes. Ainsi, la chirurgie vaginale garde toute sa place notamment chez des patientes âgées n'ayant plus d'activité sexuelle. La voie d'abord doit donc s'adapter aux caractéristiques cliniques de la patiente, et son choix être une décision partagée après information appropriée.

Characterization of a temporoparietal junction subtype of Alzheimer's disease.

Alzheimer's disease (AD) subtypes have been described according to genetics, neuropsychology, neuropathology, and neuroimaging. Thirty-one patients with clinically probable AD were selected based on perisylvian metabolic decrease on FDG-PET. They were compared to 25 patients with a typical pattern of decreased posterior metabolism. Tree-based machine learning was used on those 56 images to create a classifier that was subsequently applied to 207 Alzheimer's Disease Neuroimaging Initiative (ADNI) patients with AD. Machine learning was also used to discriminate between the two ADNI groups based on neuropsychological scores. Compared to AD patients with a typical precuneus metabolic decrease, the new subtype showed stronger hypometabolism in the temporoparietal junction. The classifier was able to distinguish the two groups in the ADNI population. Both groups could only be distinguished cognitively by Trail Making Test-A scores. This study further confirms that there is more than a typical metabolic pattern in probable AD with amnestic presentation.

A randomized controlled trial to test the efficacy of trans-tympanic injections of a sodium thiosulfate gel to prevent cisplatin-induced ototoxicity in patients with head and neck cancer.

BACKGROUND: Cisplatin-induced hearing loss is frequent and severe. Antioxidants such as sodium thiosulfate (STS) can neutralize the effects of cisplatin. The objective of the trial was to test the efficacy of trans-tympanic injections of a STS gel to prevent cisplatin-induced ototoxicity. METHODS: Eligible participants were newly diagnosed patients with stage III or IV squamous cell carcinoma of the mouth, oropharynx, hypopharynx, or larynx and scheduled to be treated by concurrent chemoradiation (CCR). Patients with asymmetric hearing were not eligible. The planed treatment included cisplatin 100 mg/m2 at days 1, 22 and 43. A baseline pre-treatment complete audiometric evaluation (pure tone at frequencies ranging from 0.5 to 14 kHz, bone conduction at 0.5-4 kHz and DPOAEs) was performed. Adverse effects were noted according to CTCAE. On the day before the beginning of CCR, eligible and consenting patients were randomized to receive a trans-tympanic injection of the gel either in the left ear or in the right ear. A final post-treatment complete audiometric evaluation was scheduled to be performed 1 month after the end of CCR by audiologists kept blind to the ear assignment. For the main outcome, the permanent threshold shift (PTS) in decibel (dB) was calculated as the difference between the final and baseline measures at all pure tone frequencies at 0.5-14 kHz for each patient and for each ear. The main outcome was assessed blindly in a mixed linear model with the PTS as the dependent variable and intervention, frequency, their interaction and radiation dose to the cochlea as independent variables. RESULTS: Between January 2015 and April 2016, 13 patients were randomized. The trial was stopped in June 2016 for poor accrual. The average loss of hearing over all frequencies was 1.3 dB less for treated ears compared to control ears. Although not statistically (p = 0.61) nor clinically significant, the difference was in favor of the treated ears for all frequencies between 3 and 10 kHz. CONCLUSIONS: Our trial suggests that STS deposited on the round window was safe for the middle and inner ears. More work is needed to improve the efficacy of trans-tympanic injections of cisplatin antidotes. TRIAL REGISTRATION: ClinicalTrials.gov, NTC02281006 , Registered 3 November 2014.

Predictors of circulating INTERLEUKIN-6 levels in head and neck cancer patients.

BACKGROUND: Circulating interleukin-6 (IL-6) improves outcome prediction for second primary cancer (SPC) in head and neck cancer (HNC) patients. This study aimed to identify factors associated with IL-6 serum levels in HNC patients. METHODS: This study was conducted as part of a phase III chemoprevention trial. IL-6 was measured using chemiluminescent immunometric assay on pretreatment serum sample obtained from 527 stage I-II HNC patients. Patients' lifestyle habits, sociodemographic, medical and tumor characteristics were evaluated before radiation therapy (RT). Factors independently associated with IL-6 levels before RT were identified using multiple linear regression. RESULTS: The median IL-6 serum level was 3.1 ng/L. In the multivariate analysis, eight factors were significantly associated (p < 0.05) with IL-6: age, gender, marital status, body mass index, tobacco consumption, comorbidities, Karnofsky Performance Status and HNC site. Smoking duration and lifetime pack-years were positively associated with IL-6 serum levels in a dose-response relationship (p-value for trend ≤0.03). CONCLUSIONS: Circulating IL-6 is a strong predictor of the occurrence of SPC in HNC patients. We identified eight factors independently associated with serum IL-6 levels in 527 stage I-II HNC patients.The dose-response relationship between lifetime smoking and IL-6 serum levels suggested a causal role of tobacco exposure on IL-6 production. Further studies are needed to establish whether the effect of tobacco exposure on SPC could be partly mediated by IL-6, a pro-inflammatory cytokine.

Prediction of the outcome of children who had a language delay at age 2 when they are aged 4: Still a challenge.

PURPOSE: This study investigated the role that variables related to children and their environment play in the prediction of outcomes at 4 years of age for children with a language delay at 2 years. METHOD: A longitudinal study was undertaken where 64 children (45 boys, 19 girls; mean age = 53.3 months; SD = 4.4) with language delay at age 2 years were re-evaluated at age 4 years. Three developmental trajectories were analysed. RESULT: The early stages of grammar, as estimated by mean length of utterance at 3.5 years, are an important prognosis factor of subsequent language impairment (LI). Children who are exposed to several risk factors simultaneously are more likely to have a language delay (LD) or a LI, but the profile of LD children is more akin to that of the typically developing (TD) children. Children with LI tend to have profiles with a greater number of risk factors. CONCLUSION: The results of this study encourage different intervention approaches depending on the child's language profile at 2 years, due to differing language prognosis. The results also point to the need to assess the child's environment. Future studies with large diverse population samples may give more precise information on potential risk factors and their cumulative effect.

A latent low-dimensional common input drives a pool of motor neurons: a probabilistic latent state-space model.

Motor neurons appear to be activated with a common input signal that modulates the discharge activity of all neurons in the motor nucleus. It has proven difficult for neurophysiologists to quantify the variability in a common input signal, but characterization of such a signal may improve our understanding of how the activation signal varies across motor tasks. Contemporary methods of quantifying the common input to motor neurons rely on compiling discrete action potentials into continuous time series, assuming the motor pool acts as a linear filter, and requiring signals to be of sufficient duration for frequency analysis. We introduce a space-state model in which the discharge activity of motor neurons is modeled as inhomogeneous Poisson processes and propose a method to quantify an abstract latent trajectory that represents the common input received by motor neurons. The approach also approximates the variation in synaptic noise in the common input signal. The model is validated with four data sets: a simulation of 120 motor units, a pair of integrate-and-fire neurons with a Renshaw cell providing inhibitory feedback, the discharge activity of 10 integrate-and-fire neurons, and the discharge times of concurrently active motor units during an isometric voluntary contraction. The simulations revealed that a latent state-space model is able to quantify the trajectory and variability of the common input signal across all four conditions. When compared with the cumulative spike train method of characterizing common input, the state-space approach was more sensitive to the details of the common input current and was less influenced by the duration of the signal. The state-space approach appears to be capable of detecting rather modest changes in common input signals across conditions.NEW & NOTEWORTHY We propose a state-space model that explicitly delineates a common input signal sent to motor neurons and the physiological noise inherent in synaptic signal transmission. This is the first application of a deterministic state-space model to represent the discharge characteristics of motor units during voluntary contractions.

A genome-wide association study of non-HPV-related head and neck squamous cell carcinoma identifies prognostic genetic sequence variants in the MAP-kinase and hormone pathways.

BACKGROUND: Carcinomas of the oral cavity, pharynx and larynx are referred to as head and neck cancers (HNC); together they account for 2-3% of all newly diagnosed cancers in North America. Between 40-50% of HNC are early diagnosed at stages I-II. The 5-year and 10-year relative survival rates are 61% and 50%, respectively. Germline genetic sequence variants (GSV) have become increasingly found to have prognostic implications in a variety of cancers. Identifying these variants may have important clinical and biological implications. METHODS: We conducted a genome-wide association study (GWAS) in 531 Stage I-II radiation-treated HNC patients (originally recruited for α-tocopherol/ß-carotene placebo-controlled secondary prevention study) and used a replication cohort of 566 HNC patients of all stages, of mostly non-HPV-related cancers. Survival rates were estimated by the Kaplan-Meier method. Cox proportional hazards models adjusted for potential clinical factors and principal components were used to test for associations between the GSV and overall survival (OS) in these tumors. RESULTS: The median follow-up time for OS was 9.21 years (GWAS cohort) and 2.37 years (replication cohort). In both cohorts, CACNA2D1:rs2299187, ESRRG:rs946465 and ESRRG:rs1416612 were each individually significantly associated with survival. In silico analysis of ESRRG:rs946465 identifies that it produces a splice variant in ESRRG. Variant alleles of CACNA2D1:rs2299187 and ESRRG:rs946465 were associated with higher expression of the corresponding protein. CONCLUSIONS: Putatively functional polymorphisms in the MAP-Kinase and estrogen pathways, identified through GWAS and replicated in an independent dataset were associated with the survival of HNC patients.

Implementing efficient and sustainable collaboration between National Immunization Technical Advisory Groups: Report on the 3rd International Technical Meeting, Paris, France, 8-9 December 2014.

Many experts on vaccination are convinced that efforts should be made to encourage increased collaboration between National Immunization Technical Advisory Groups on immunization (NITAGs) worldwide. International meetings were held in Berlin, Germany, in 2010 and 2011, to discuss improvement of the methodologies for the development of evidence-based vaccination recommendations, recognizing the need for collaboration and/or sharing of resources in this effort. A third meeting was held in Paris, France, in December 2014, to consider the design of specific practical activities and an organizational structure to enable effective and sustained collaboration. The following conclusions were reached: (i) The proposed collaboration needs a core functional structure and the establishment or strengthening of an international network of NITAGs. (ii) Priority subjects for collaborative work are background information for recommendations, systematic reviews, mathematical models, health economic evaluations and establishment of common frameworks and methodologies for reviewing and grading the evidence. (iii) The programme of collaborative work should begin with participation of a limited number of NITAGs which already have a high level of expertise. The amount of joint work could be increased progressively through practical activities and pragmatic examples. Due to similar priorities and already existing structures, this should be organized at regional or subregional level. For example, in the European Union a project is funded by the European Centre for Disease Prevention and Control (ECDC) with the aim to set up a network for improving data, methodology and resource sharing and thereby supporting NITAGs. Such regional networking activities should be carried out in collaboration with the World Health Organization (WHO). (iv) A global steering committee should be set up to promote international exchange between regional networks and to increase the involvement of less experienced NITAGs. NITAGs already collaborate at the global level via the NITAG Resource Centre, a web-based platform developed by the Health Policy and Institutional Development Unit (WHO Collaborating Centre) of the Agence de Médecine Préventive (AMP-HPID). It would be appropriate to continue facilitating the coordination of this global network through the AMP-HPID NITAG Resource Centre. (v) While sharing work products and experiences, each NITAG would retain responsibility for its own decision-making and country-specific recommendations.

Randomized non-inferiority trial of Bicalutamide and Dutasteride versus LHRH agonists for prostate volume reduction prior to I-125 permanent implant brachytherapy for prostate cancer.

OBJECTIVE: To determine the efficacy and toxicity of a 3-month regimen of Dutasteride and Bicalutamide compared to LHRH agonists for prostate volume (PV) reduction prior to permanent implant prostate brachytherapy (PIPB). MATERIAL AND METHODS: Patients with low-risk or low-tier intermediate risk prostate cancer eligible for PIPB with a prostate volume greater than 50 cc were randomized to either Dutasteride 0.5 mg Bicalutamide 50 mg daily and Tamoxifen 10 mg daily for 3 months (D+B group) or to a 3 month dose of an LHRH agonist and Bicalutamide daily for 1 month (LHRH group). Their PV was measured at baseline and at pre-implant. Non-inferiority analysis was completed for the relative (%) PV reduction. IPSS and EPIC questionnaires were completed at baseline, pre-implant and at 1, 3, 6, 12, 18 and 24 months post-treatment. IPSS and EPIC comparisons were based on superiority analysis RESULTS: 60 patients were randomized (31 to LHRH group and 29 to D+B group). Mean relative PV reduction (SD) was 35.5% (8.9) in the LHRH group and 31.7% (9.6) in the D+B group. The upper bound of the 95% confidence for the interval for the difference between groups favouring LHRH agonists for PV reduction was 8.6 which did not cross the 10% non-inferiority margin meaning D+B is non-inferior to LHRH agonist for PV reduction, although 5/29 (17%) of those in the D+B group required longer duration of D+B to achieve adequate volume reduction. There were no statistically significant differences in IPSS scores over the entire follow-up period. EPIC sexual summary score was significantly better in the D+B group at pre-implant, 1 month, 3 months post-implant. CONCLUSION: Dutasteride and Bicalutamide is a regimen of non-inferior efficacy to LHRH agonist based regimens for prostate volume reduction prior to permanent implant prostate brachytherapy. D+B has less sexual toxicity compared to LHRH agonists prior to implant and for the first 6 months after implant. D+B is therefore an option to be considered for prostate volume reduction prior to PIPB.

Age-related changes in slow wave activity rise time and NREM sleep EEG with and without zolpidem in healthy young and older adults.

OBJECTIVE: Whether there are age-related changes in slow wave activity (SWA) rise time, a marker of homeostatic sleep drive, is unknown. Additionally, although sleep medication use is highest among older adults, the quantitative electroencephalographic (EEG) profile of the most commonly prescribed sleep medication, zolpidem, in older adults is also unknown. We therefore quantified age-related and regional brain differences in sleep EEG with and without zolpidem. METHODS: Thirteen healthy young adults aged 21.9 ± 2.2 years and 12 healthy older adults aged 67.4 ± 4.2 years participated in a randomized, double-blind, within-subject study that compared placebo to 5 mg zolpidem. RESULTS: Older adults showed a smaller rise in SWA and zolpidem increased age-related differences in SWA rise time such that age differences were observed earlier after latency to persistent sleep. Age-related differences in EEG power differed by brain region. Older, but not young, adults showed zolpidem-dependent reductions in theta and alpha frequencies. Zolpidem decreased stage 1 in older adults and did not alter other age-related sleep architecture parameters. CONCLUSIONS: SWA findings provide additional support for reduced homeostatic sleep drive or reduced ability to respond to sleep drive with age. Consequences of reduced power in theta and alpha frequencies in older adults remain to be elucidated.