Basic Science and Pathogenesis.

Background: Aging is the main risk factor of cognitive neurodegenerative diseases such as Alzheimer's disease, with epigenome alterations as a contributing factor, however, it is not clear which biological mechanisms are common or disease-specific. Here we investigated epigenomic/genomic signatures in the hippocampus of mouse models of aging and of tauopathy, an AD-related feature.

Methods: Aging was modelled by comparing 18-month- versus 3-month-old WT mice.

Basic Science and Pathogenesis.

Background: PhospholipaseC γ2 (PLCG2) is known to have direct link with genetic risk factors for Alzheimer's like dementia (AD). PLCG2 has been previously demonstrated to have association with Aß uptake through microglia. And mostly expressed in dentate gyrus (DG) network of hippocampus.

Basic Science and Pathogenesis.

Background: P-tau217 has emerged as a compelling alternative to long-established p-tau181 to accurately measure tau modifications in biofluids in response to brain Abeta and tau deposition in Alzheimer's disease (AD). Understanding the specificity and significance of p-tau217 changes over AD stages is critical to interpret its potential response to treatments against Abeta and tau aggregation.

Methods: We measured p-tau217 phosphorylation by mass spectrometry.

Basic Science and Pathogenesis.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare, hereditary cerebrovascular disease which causes stroke, complex migraine, and cognitive impairment. Given its monogenic nature, CADASIL is considered a 'pure' model of small vessel disease and vascular dementia. CADASIL is caused by NOTCH3 pathogenic variants with a broad resulting phenotypic spectrum.

Basic Science and Pathogenesis.

Background: Protein metabolism and turnover can be monitored using tracer methods, notably stable isotope labeling kinetics (SILK) based on 13C-leucine incorporation. This approach has been used in Alzheimer's disease, specifically analyzing the turnover in cerebrospinal fluid of biomarkers of interest, including amyloid peptides, leading to major pathophysiological insights (Nature medicine 12:856-861). This was achieved using immunoprecipitation mass spectrometry, which enables to track a small number of targets present in low concentration.

Basic Science and Pathogenesis.

Background: Amyloid-targeting antibodies have been shown to be remarkably effective at clearing amyloid plaques from the Alzheimer's disease (AD) brain. To date, preclinical assessments have used animal models that develop only amyloid pathology, whereas AD patients present with tau pathology, neuroinflammation, and other concurrent neuropathologies. Deciphering how successful anti-amyloid therapies impact the synergistic interplay of amyloid and tau will be critical in determining which secondary disease processes can be slowed, interrupted, or reversed by amyloid-targeting immunotherapies.

Basic Science and Pathogenesis.

Background: Over-representation of several health conditions (such as diabetes, hearing loss, etc) have been identified up to 15 years before Alzheimer's Disease (AD) diagnosis through the study of electronic health records [1]. Mechanisms underlying these associations remain elusive. We propose to study the associations between these co-pathologies (proxied by genetic risk scores), and the physiological and clinical evolution of AD patients.

Clinical Manifestations.

Future clinical trials targeting Alzheimer's disease (AD) on new disease modifying drugs necessitate a paradigm shift towards early identification of individuals at risk. Emerging evidence indicates that subtle alterations in language and speech characteristics may manifest concurrently with the progression of neurodegenerative disorders like AD. These changes manifest as discernible variations, assessable through semantic nuances, word choices, sentiment, grammar usage (linguistic features), and phonetic/acoustic traits (paralinguistic features).

Clinical Manifestations.

Background: While Alzheimer Disease (AD) patients' difficulty to recognize face identity (Werheid & Clare, 2007) has been mainly attributed to episodic and semantic memory impairments, these patients can also show abnormal difficulties at matching of unfamiliar faces for their identity, suggesting impaired perceptual function (Lavallée et al., 2016). However, since this latter evidence is based on explicit behavioural measures, the difficulties of AD patients can be due to many factors (e.

Clinical Manifestations.

Background: Changes in speech and language functions have shown to be early symptoms of AD pathology. Recent developments in automatic speech and language processing have opened avenues for objective assessments of these changes. The primary objective of this study is to explore whether speech and language markers extracted from cognitive testing conducted during an automated phone call differ according to underlying AD pathology as measured in cerebrospinal fluid (CSF) in preclinical or early stage individuals.

Clinical Manifestations.

Background: In cognitively unimpaired (CU) older adults, the presence of a subjective cognitive decline (SCD) combined with evidence of abnormal b-amyloid (Ab) is proposed as stage 2 of Alzheimer's disease (AD) by the NIA-AA framework (Jack et al., 2018). However, the associations found between SCD and preclinical AD are inconsistent across studies, highlighting the importance of better understanding which specific SCD features are associated with either Ab or tau burden.

Clinical Manifestations.

Background: Speech and language impairments are associated with cognitive decline in neurodegenerative dementias, particularly Alzheimer's Disease (AD), where subtle speech changes may precede clinical dementia onset. As clinical trials prioritize early identification for disease-modifying treatments, digital biomarkers for timely screening become imperative. Digital speech-based biomarkers can be employed for screening populations at the earliest AD stages.

Effect of Apical Preparation Size and Preparation Taper on Smear Layer Removal Using Two Different Irrigation Needles: A Scanning Electron Microscopy Study.

Objectives:  The aim of this study was to determine the effect of apical preparation size and preparation taper on smear layer removal using a metallic needle and a new polymer needle (IrriFlex, Produits Dentaires SA "PD," Vevey, Switzerland).

Materials And Methods:  One hundred and eight single-rooted teeth with one canal were randomly divided into four groups according to the preparation and irrigation needle used: G1-30, 0.04 and IrriFlex ( = 25); G2-25, 0.

Clinical Manifestations.

Background: Over the past years, social cognition has been envisaged as a promising domain to distinguish behavioral variant frontotemporal degeneration (bvFTD) from its main differential diagnoses that is primary psychiatric disorders (PPD). The core-processes approach, which has emphasized the importance of emotion recognition and mentalizing, has been particularly useful to better characterize each condition and enhance the earliness of FTD's diagnosis. However, new findings evidencing conflicting results regarding the ability of social cognition to distinguish bvFTD from PPD have underlined the importance of moving beyond the core processes approach.

Clinical Manifestations.

Background: Cognitive complaints (CC) refer to a reported experience of cognitive decline and are recognized as a potential precursor to future functional decline and progression to dementia. Identifying individuals with CC may be a valuable opportunity for preventive measures, early detection, and intervention strategies to address dementia risk. However, the characteristics of CC and its associated risk of progression to dementia are highly heterogeneous, influenced significantly by CC identification methods, recruitment approaches, and attrition in longitudinal cohort studies.

Clinical Manifestations.

Background: Traditional pen-and-paper neuropsychological assessments fail to capture subtle cognitive changes in the early stages of Alzheimer's disease (AD). Remote and unsupervised digital assessments available on smartphones, tablets, and personal computers may offer a solution to this by increasing the amount and types of data available to researchers and clinicians, while simultaneously improving ecological validity and alleviating patient burden. As these remote and unsupervised digital cognitive assessment tools become more widely available, it is important that they are validated in a systematic way.

Clinical Manifestations.

Background: Anosognosia, a hallmark of Alzheimer's disease (AD), manifests as a gradual decline in disease awareness, yet its neural correlates remain unclear. This study investigates how amyloid accumulation, glucose hypometabolism and cortical atrophy relate to cognitive awareness across the AD continuum. Both the pathological processes and the brain regions involved were studied.

Clinical Manifestations.

Background: Mild parkinsonian signs (MPS) are prevalent in older adults and linked to an increased risk of dementia. However, their association with Motoric Cognitive Risk syndrome (MCR), a pre-dementia syndrome characterized by slow gait speed and cognitive complaints, is unclear. This study aims to examine the association of MPS with incident MCR.

Metastability of a Periodic Network of Threads: Shapes of a Knitted Fabric.

Knitted fabrics are metamaterials with remarkable mechanical properties, such as extreme deformability and multiple history-dependent rest shapes. This Letter shows that those properties may stem from a continuous set of metastable states for a fabric free of external forces. This is evidenced through experiments, numerical simulations, and analytical developments.

Quantum Error-Correcting Codes with a Covariant Encoding.

Given some group G of logical gates, for instance the Clifford group, what are the quantum encodings for which these logical gates can be implemented by simple physical operations, described by some physical representation of G? We study this question by constructing a general form of such encoding maps. For instance, we recover that the ⟦5,1,3⟧ and Steane codes admit transversal implementations of the binary tetrahedral and binary octahedral groups, respectively. For bosonic encodings, we show how to obtain the GKP and cat qudit encodings by considering the appropriate groups, and essentially the simplest physical implementations.

Reinforcement Learning Optimization of the Charging of a Dicke Quantum Battery.

Quantum batteries are energy-storing devices, governed by quantum mechanics, that promise high charging performance thanks to collective effects. Because of its experimental feasibility, the Dicke battery-which comprises N two-level systems coupled to a common photon mode-is one of the most promising designs for quantum batteries. However, the chaotic nature of the model severely hinders the extractable energy (ergotropy).

Spin Waves and Three Dimensionality in the High-Pressure Antiferromagnetic Phase of SrCu_{2}(BO_{3})_{2}.

Quantum magnetic materials can provide explicit realizations of paradigm models in quantum many-body physics. In this context, SrCu_{2}(BO_{3})_{2} is a faithful realization of the Shastry-Sutherland model for ideally frustrated spin dimers, even displaying several of its quantum magnetic phases as a function of pressure. We perform inelastic neutron scattering measurements on SrCu_{2}(BO_{3})_{2} at 5.

Energy-Filtered Quantum States and the Emergence of Nonlocal Correlations.

Energy-filtered quantum states are promising candidates for efficiently simulating thermal states. We explore a protocol designed to transition a product state into an eigenstate located in the middle of the spectrum; this is achieved by gradually reducing its energy variance, which allows us to comprehensively understand the crossover phenomenon and the subsequent convergence toward thermal behavior. We introduce and discuss three energy-filtering regimes (short, medium, and long), and we interpret them as stages of thermalization.

Search for Fractionally Charged Particles with CUORE.

The Cryogenic Underground Observatory for Rare Events (CUORE) is a detector array comprised by 988 5  cm×5  cm×5  cm TeO_{2} crystals held below 20 mK, primarily searching for neutrinoless double-beta decay in ^{130}Te. Unprecedented in size among cryogenic calorimetric experiments, CUORE provides a promising setting for the study of exotic throughgoing particles. Using the first tonne year of CUORE's exposure, we perform a search for hypothesized fractionally charged particles (FCPs), which are well-motivated by various standard model extensions and would have suppressed interactions with matter.

Clinical Manifestations.

Background: Seizures, traumatic brain injury (TBI), and dementia increase in prevalence with age. However, the role of seizure and TBI on cognitive impairment risk (CI) is unclear. This study investigated how a diagnosis of seizures and TBI was associated with the progression to CI and assessed the role of medications.