Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease.

The advancement of disease-modifying treatments (DMTs) for Alzheimer's disease (AD), along with the approval of three amyloid-targeting therapies in the US and several other countries, represents a significant development in the treatment landscape, offering new hope for addressing this once untreatable chronic progressive disease. However, significant challenges persist that could impede the successful integration of this class of drugs into clinical practice. These challenges include determining patient eligibility, appropriate use of diagnostic tools and genetic testing in patient care pathways, effective detection and monitoring of side effects, and improving the healthcare system's readiness by engaging both primary care and dementia specialists.

The Excess of Carriers in Rare Disorders Suggests a Nonpathogenic Effect for Most Variants of Uncertain Significance.

Functional annotation and interpretation of genetic variants are a critical step in genetic diagnosis, as it may lead to personalized therapeutic options and genetic counseling. While the number of confirmed pathogenic genetic variants in an individual is relatively low, the number of variants of uncertain significance (VOUS) can be considerably higher, increasing the number of potential carriers of genetic disorders. Thus, reducing uncertainty and assessing the real effect of VOUS are crucial for clinical and medical genetics.

Resting-State Functional Connectivity Profile of Insular Subregions.

The insula is often considered the fifth lobe of the brain and is increasingly recognized as one of the most connected regions in the brain, with widespread connections to cortical and subcortical structures. As a follow-up to our previous tractography work, we investigated the resting-state functional connectivity (rsFC) profiles of insular subregions and assessed their concordance with structural connectivity. We used the CONN toolbox to analyze the rsFC of the same 19 insular regions of interest (ROIs) we used in our prior tractography work and regrouped them into six subregions based on their connectivity pattern similarity.

Neuropsychological Assessment for Early Detection and Diagnosis of Dementia: Current Knowledge and New Insights.

Dementia remains an underdiagnosed syndrome, and there is a need to improve the early detection of cognitive decline. This narrative review examines the role of neuropsychological assessment in the characterization of cognitive changes associated with dementia syndrome at different states. The first section describes the early indicators of cognitive decline and the major barriers to their identification.

Validating the Spanish translation of the posttraumatic stress disorder checklist (PCL-5) in a sample of individuals with traumatic brain injury.

Introduction: There is controversy regarding the comorbidity of posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI). The present study translated the PTSD Checklist for DSM-5 (PCL-5) to Spanish and validated it in a sample of patients with TBI 6 months after the injury.

Methods: The study included 233 patients (162 males and 71 females) recruited from four Spanish hospitals within 24 h of traumatic brain injury.

Mapping brain state-dependent sensory responses across the mouse cortex.

Sensory information must be integrated across a distributed brain network for stimulus processing and perception. Recent studies have revealed specific spatiotemporal patterns of cortical activation for the early and late components of sensory-evoked responses, which are associated with stimulus features and perception, respectively. Here, we investigated how the brain state influences the sensory-evoked activation across the mouse cortex.

Early Unguided Human Brain Organoid Neurovascular Niche Modeling into the Permissive Chick Embryo Chorioallantoic Membrane.

Engrafting organoids into vascularized tissues in model animals, such as the immunodeficient mouse or chick embryo chorioallantoic membrane (CAM), has proven efficient for neovascularization modeling. The CAM is a richly vascularized extraembryonic membrane, which shows limited immunoreactivity, thus becoming an excellent hosting model for human origin cell transplants. This paper describes the strategy to engraft human brain organoids differentiated at multiple maturation stages into the CAM.

Physical Performance and Amyloid-β in Humans: A Systematic Review and Meta-Analysis of Observational Studies.

Background: Accumulation of amyloid-β (Aβ) plaques is one of the main features of Alzheimer's disease (AD). Physical performance has been related to dementia risk and Aβ, and it has been hypothesized as one of the mechanisms leading to greater accumulation of Aβ. Yet, no evidence synthesis has been performed in humans.

CAAStools: a toolbox to identify and test Convergent Amino Acid Substitutions.

Motivation: Coincidence of Convergent Amino Acid Substitutions (CAAS) with phenotypic convergences allow pinpointing genes and even individual mutations that are likely to be associated with trait variation within their phylogenetic context. Such findings can provide useful insights into the genetic architecture of complex phenotypes.

Results: Here we introduce CAAStools, a set of bioinformatics tools to identify and validate CAAS in orthologous protein alignments for predefined groups of species representing the phenotypic values targeted by the user.

Proteomics analysis of circulating small extracellular vesicles: Focus on the contribution of EVs to tumor metabolism.

The term small extracellular vesicle (sEV) is a comprehensive term that includes any type of cell-derived, membrane-delimited particle that has a diameter < 200 nm, and which includes exosomes and smaller microvesicles. sEVs transfer bioactive molecules between cells and are crucial for cellular homeostasis and particularly during tumor development, where sEVs provide important contributions to the formation of the premetastic niche and to their altered metabolism. sEVs are thus legitimate targets for intervention and have also gained increasing interest as an easily accessible source of biomarkers because they can be rapidly isolated from serum/plasma and their molecular cargo provides information on their cell-of origin.

Spanish normative studies (NEURONORMA-Plus project): norms for the Delis Kaplan-Design Fluency Test, Color Trails Test, and Dual Task.

Introduction: Complex attention and non-verbal fluency tasks are used in neuropsychological assessments with the aim of exploring subdomains of executive function. The purpose of this study is to provide norms and age-, education-, and sex-adjusted data for the Delis Kaplan-Design Fluency Test (DK-DFT), Color Trails Test (CTT), and Dual Task (DT) as part of the NEURONORMA-Plus project.

Methods: The sample included 308 cognitively unimpaired individuals aged between 18 and 92 years.

Spanish normative studies (NEURONORMA-Plus project): norms for the Wisconsin Card Sorting Test, the Modified Taylor Complex Figure, and the Ruff-Light Trail Learning Test.

Objective: The present study aims to provide norms and age-, education-, and sex-adjusted data for the Wisconsin Card Sorting Test (WCST), the Modified Taylor Complex Figure (MTCF), and the Ruff-Light Trail Learning Test (RULIT) as part of the NEURONORMA-Plus project.

Methods: We recruited 308 cognitively healthy individuals aged between 18 and 92 years. Tables are provided to convert raw scores to age-adjusted scaled scores, as well as adjustments for education and sex after applying independent regression models in 2 age groups (< 50 and ≥ 50 years).

CSF proteomics in autosomal dominant Alzheimer's disease highlights parallels with sporadic disease.

Autosomal dominant Alzheimer's disease (ADAD) offers a unique opportunity to study pathophysiological changes in a relatively young population with few comorbidities. A comprehensive investigation of proteome changes occurring in ADAD could provide valuable insights into AD-related biological mechanisms and uncover novel biomarkers and therapeutic targets. Furthermore, ADAD might serve as a model for sporadic AD, but in-depth proteome comparisons are lacking.

A global catalog of whole-genome diversity from 233 primate species.

The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology and is urgent given severe threats these species are facing. Here, we present high-coverage whole-genome data from 233 primate species representing 86% of genera and all 16 families.

The landscape of tolerated genetic variation in humans and primates.

Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans.

The landscape of tolerated genetic variation in humans and primates.

Unlabelled: Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole genome sequencing data for 809 individuals from 233 primate species, and identified 4.3 million common protein-altering variants with orthologs in human.

Discovery of novel CSF biomarkers to predict progression in dementia using machine learning.

Providing an accurate prognosis for individual dementia patients remains a challenge since they greatly differ in rates of cognitive decline. In this study, we used machine learning techniques with the aim to identify cerebrospinal fluid (CSF) biomarkers that predict the rate of cognitive decline within dementia patients. First, longitudinal mini-mental state examination scores (MMSE) of 210 dementia patients were used to create fast and slow progression groups.

[Effectiveness of a psychotherapeutic intervention group program in the improvement of caregiver well-being in Alzheimer's disease patients' family caregivers: the CuiDem study].

Introduction: Caregivers of patients with Alzheimer's Disease experience physical and emotional burnout that can be treated with non-pharmacological interventions.

Aim: Assess the efficacy of a group cognitive behavioural psychotherapeutic intervention, for improving well-being perception in caregivers, compared to a support group. Also, we assessed its efficacy after a follow-up period of 1-year post-intervention.

Effect of an 18-Month Meditation Training on Regional Brain Volume and Perfusion in Older Adults: The Age-Well Randomized Clinical Trial.

Importance: No lifestyle-based randomized clinical trial directly targets psychoaffective risk factors of dementia. Meditation practices recently emerged as a promising mental training exercise to foster brain health and reduce dementia risk.

Objective: To investigate the effects of meditation training on brain integrity in older adults.

Functional connectivity of brain networks with three monochromatic wavelengths: a pilot study using resting-state functional magnetic resonance imaging.

Exposure to certain monochromatic wavelengths can affect non-visual brain regions. Growing research indicates that exposure to light can have a positive impact on health-related problems such as spring asthenia, circadian rhythm disruption, and even bipolar disorders and Alzheimer's. However, the extent and location of changes in brain areas caused by exposure to monochromatic light remain largely unknown.

Brain transcriptomic profiling reveals common alterations across neurodegenerative and psychiatric disorders.

Neurodegenerative and neuropsychiatric disorders (ND-NPs) are multifactorial, polygenic and complex behavioral phenotypes caused by brain abnormalities. Large-scale collaborative efforts have tried to identify the genetic architecture of these conditions. However, the specific and shared underlying molecular pathobiology of brain illnesses is not clear.