Neuronal A2A receptor exacerbates synapse loss and memory deficits in APP/PS1 mice.

Early pathological upregulation of adenosine A2A receptors (A2ARs), one of the caffeine targets, by neurons is thought to be involved in the development of synaptic and memory deficits in Alzheimer's disease (AD) but mechanisms remain ill-defined. To tackle this question, we promoted a neuronal upregulation of A2AR in the hippocampus of APP/PS1 mice developing AD-like amyloidogenesis. Our findings revealed that the early upregulation of A2AR in the presence of an ongoing amyloid pathology exacerbates memory impairments of APP/PS1 mice.

Qualitative versus quantitative assessment of electroencephalography in cognitive decline: Comparison in a clinical population.

This study aimed to compare the diagnostic performance of visual assessment of electroencephalography (EEG) using the Grand Total EEG (GTE) score and quantitative EEG (QEEG) using spectral analysis in the context of cognitive impairment. This was a retrospective study of patients with mild cognitive impairment, with (MCI+V) or without (MCI) vascular dysfunction, and patients with dementia including Alzheimer's disease, Lewy Body Dementia and vascular dementia. The results showed that the GTE is a simple scoring system with some potential applications, but limited ability to distinguish between dementia subtypes, while spectral analysis appeared to be a powerful tool, but its clinical development requires the use of artificial intelligence tools.

Catatonia in patients with dementia: A descriptive study of clinical profiles and treatment response.

Background: Catatonia is a highly prevalent syndrome in patients presenting with major neurocognitive disorders (dementia). In this study, we aim to provide a comprehensive description of the clinical and therapeutic aspects of catatonia in patients with dementia.

Method: This descriptive study, conducted between September 2015 and June 2022, collected data from 25 patients diagnosed with dementia, out of 143 patients treated for catatonia in our specialized psychiatry department.

A 3D convolutional neural network to classify subjects as Alzheimer's disease, frontotemporal dementia or healthy controls using brain 18F-FDG PET.

With the arrival of disease-modifying drugs, neurodegenerative diseases will require an accurate diagnosis for optimal treatment. Convolutional neural networks are powerful deep learning techniques that can provide great help to physicians in image analysis. The purpose of this study is to introduce and validate a 3D neural network for classification of Alzheimer's disease (AD), frontotemporal dementia (FTD) or cognitively normal (CN) subjects based on brain glucose metabolism.

Assessment of Mendelian and risk-factor genes in Alzheimer disease: A prospective nationwide clinical utility study and recommendations for genetic screening.

Purpose: To assess the likely pathogenic/pathogenic (LP/P) variants rates in Mendelian dementia genes and the moderate-to-strong risk factors rates in patients with Alzheimer disease (AD).

Methods: We included 700 patients in a prospective study and performed exome sequencing. A panel of 28 Mendelian and 6 risk-factor genes was interpreted and returned to patients.

Continuous positive airway pressure compliance in patients with mild cognitive impairment.

Purpose: Sleep apnoea (SA) is associated with accelerated cognitive decline in patients with mild cognitive impairment (MCI). Treatment of SA by continuous positive airway pressure (CPAP) may slow this decline if patients comply with the treatment. The aim of this study was to assess the rate of CPAP compliance in this population.

Cerebral Metabolic Signature of Chronic Benzodiazepine Use in Nondemented Older Adults: An FDG-PET Study in the MEMENTO Cohort.

Objective: We sought to examine the association between chronic Benzodiazepine (BZD) use and brain metabolism obtained from 2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography (PET) in the MEMENTO clinical cohort of nondemented older adults with an isolated memory complaint or mild cognitive impairment at baseline.

Methods: Our analysis focused on 3 levels: (1) the global mean brain standardized uptake value (SUVR), (2) the Alzheimer's disease (AD)-specific regions of interest (ROIs), and (3) the ratio of total SUVR on the brain and different anatomical ROIs. Cerebral metabolism was obtained from 2-deoxy-2-fluoro-D-glucose-FDG-PET and compared between chronic BZD users and nonusers using multiple linear regressions adjusted for age, sex, education, APOE ε 4 copy number, cognitive and neuropsychiatric assessments, history of major depressive episodes and antidepressant use.

The role of adenosine A receptors in Alzheimer's disease and tauopathies.

Adenosine signals through four distinct G protein-coupled receptors that are located at various synapses, cell types and brain areas. Through them, adenosine regulates neuromodulation, neuronal signaling, learning and cognition as well as the sleep-wake cycle, all strongly impacted in neurogenerative disorders, among which Alzheimer's Disease (AD). AD is a complex form of cognitive deficits characterized by two pathological hallmarks: extracellular deposits of aggregated β-amyloid peptides and intraneuronal fibrillar aggregates of hyper- and abnormally phosphorylated Tau proteins.

A Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging.

Background And Objectives: To elaborate a new algorithm to establish a standardized method to define cutoffs for CSF biomarkers of Alzheimer disease (AD) by validating the algorithm against CSF classification derived from PET imaging.

Methods: Low and high levels of CSF phosphorylated tau were first identified to establish optimal cutoffs for CSF β-amyloid (Aβ) peptide biomarkers. These Aβ cutoffs were then used to determine cutoffs for CSF tau and phosphorylated tau markers.

Caffeine intake exerts dual genome-wide effects on hippocampal metabolism and learning-dependent transcription.

Caffeine is the most widely consumed psychoactive substance in the world. Strikingly, the molecular pathways engaged by its regular consumption remain unclear. We herein addressed the mechanisms associated with habitual (chronic) caffeine consumption in the mouse hippocampus using untargeted orthogonal omics techniques.

Interoception and social cognition in chronic low back pain: a common inference disturbance? An exploratory study.

Lower interoceptive abilities are a characteristic of chronic pain conditions. Social support plays an important role in chronic low back pain (cLBP) but social cognitive skills have rarely been investigated. This study aimed to characterize interoceptive and social cognitive abilities in cLBP and to study the relationship between both domains that have been brought closer together by brain predictive coding models.

Benzodiazepine use and neuroimaging markers of Alzheimer's disease in nondemented older individuals: an MRI and 18F Florbetapir PET study in the MEMENTO cohort.

Recent evidence suggests an association between benzodiazepines (BZDs) use and lower brain amyloid load, a hallmark of AD pathophysiology. Other AD-related markers include hippocampal atrophy, but the effect of BZDs on hippocampal volume remains unclear. We aimed at 1) replicating findings on BZDs use and brain amyloid load and 2) investigating associations between BZDs use and hippocampal volume, in the MEMENTO clinical cohort of nondemented older adults with isolated memory complaint or light cognitive impairment at baseline.

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene).

LeSCoD: a new clinical scale for the detection of Lewy body disease in neurocognitive disorders.

Background: Dementia with Lewy bodies remains underdiagnosed in clinical practice mainly because of the low sensitivity of existing diagnostic criteria and a strong overlap with Alzheimer's pathology that can mask the Lewy phenotype.

Objective: The objective of this study was therefore to develop and validate a new clinical scale designed to detect signs of Lewy body disease, called LeSCoD for Lewy body Screening scale in Cognitive Disorders.

Methods: 128 patients who fulfilled the clinical criteria of dementia with Lewy bodies (DLB; n = 32), Alzheimer's disease (AD; n = 77) or both (n = 19) was prospectively enrolled.

The infantile myofibromatosis NOTCH3 L1519P mutation leads to hyperactivated ligand-independent Notch signaling and increased PDGFRB expression.

Infantile myofibromatosis (IMF) is a benign tumor form characterized by the development of nonmetastatic tumors in skin, bone, muscle and sometimes viscera. Autosomal dominant forms of IMF are caused by mutations in the gene, but a family carrying a L1519P mutation in the gene has also recently been identified. In this report, we address the molecular consequences of the NOTCH3 mutation and the relationship between the NOTCH and PDGFRB signaling in IMF.

Biomarker counseling, disclosure of diagnosis and follow-up in patients with mild cognitive impairment: A European Alzheimer's disease consortium survey.

Objectives: Mild cognitive impairment (MCI) is associated with an increased risk of further cognitive decline, partly depending on demographics and biomarker status. The aim of the present study was to survey the clinical practices of physicians in terms of biomarker counseling, management, and follow-up in European expert centers diagnosing patients with MCI.

Methods: An online email survey was distributed to physicians affiliated with European Alzheimer's disease Consortium centers (Northern Europe: 10 centers; Eastern and Central Europe: 9 centers; and Southern Europe: 15 centers) with questions on attitudes toward biomarkers and biomarker counseling in MCI and dementia.

Twenty-year trends in patient referrals throughout the creation and development of a regional memory clinic network.

Introduction: Memory clinics (MCs) are the main model for dementia diagnosis and care. Following the development of a MC network in Northern France, our objectives were to assess its impact on patient characteristics over 20 years.

Methods: The characteristics of new consultants were studied from 1997 to 2016.

Enteric synucleinopathy: from trendy concept to real entity.

An accumulating body of literature has emerged in the past 25 years to show that Parkinson's disease (PD) is not only a disorder of the brain but also of the gastrointestinal tract and more generally of the gut-brain axis. Gastrointestinal symptoms occur in almost every PD patient at some point and in nearly every case examined pathologically autopsy studies find alpha-synuclein deposits, the pathological hallmarks of PD, in the enteric nervous system. This concept of 'enteric synucleinopathy' led to the hypothesis that the enteric nervous system might play a pivotal role in the initiation and spreading of PD.

Does amnesia specifically predict Alzheimer's pathology? A neuropathological study.

Amnesia is a key component of Alzheimer's disease (AD) and the most important feature of its clinical diagnosis but its specificity has recently been challenged. This study investigated the ability of amnesia to predict AD in a clinicopathological dementia series. Ninety-one patients to which free and cued verbal memory assessment was administered during early cognitive decline, were followed until autopsy.