Sex differences in mitochondrial free-carnitine levels in subjects at-risk and with Alzheimer's disease in two independent study cohorts.

A major challenge in the development of more effective therapeutic strategies for Alzheimer's disease (AD) is the identification of molecular mechanisms linked to specific pathophysiological features of the disease. Importantly AD has a two-fold higher incidence in women than men and a protracted prodromal phase characterized by amnestic mild-cognitive impairment (aMCI) suggesting that biological processes occurring early can initiate vulnerability to AD. Here, we used a sample of 125 subjects from two independent study cohorts to determine the levels in plasma (the most accessible specimen) of two essential mitochondrial markers acetyl-L-carnitine (LAC) and its derivative free-carnitine motivated by a mechanistic model in rodents in which targeting mitochondrial metabolism of LAC leads to the amelioration of cognitive function and boosts epigenetic mechanisms of gene expression.

Cognitive, behavioral, neuroimaging and inflammatory biomarkers after hospitalization for covid-19 in Brazil.

Post-COVID-19 Condition (PCC) refers to a multisystemic syndrome that persists for months after SARS-CoV-2 infection. Cognitive deficits, fatigue, depression, and anxiety are common manifestations of the condition, but the underlying mechanisms driving these long-lasting neuropsychiatric features are still unclear. We conducted a prospective multi-method investigation of post-hospitalization COVID-19 patients in Rio de Janeiro, Brazil.

Alzheimer's disease biomarkers and their current use in clinical research and practice.

While blood-based tests are readily available for various conditions, including cardiovascular diseases, type 2 diabetes, and common cancers, Alzheimer's disease (AD) and other neurodegenerative diseases lack an early blood-based screening test that can be used in primary care. Major efforts have been made towards the investigation of approaches that may lead to minimally invasive, cost-effective, and reliable tests capable of measuring brain pathological status. Here, we review past and current technologies developed to investigate biomarkers of AD, including novel blood-based approaches and the more established cerebrospinal fluid and neuroimaging biomarkers of disease.

Changes in neuroinflammatory biomarkers correlate with disease severity and neuroimaging alterations in patients with COVID-19 neurological complications.

COVID-19 induces acute and persistent neurological symptoms in mild and severe cases. Proposed concomitant mechanisms include direct viral infection and strain, coagulopathy, hypoxia, and neuroinflammation. However, underlying molecular alterations associated with multiple neurological outcomes in both mild and severe cases are majorly unexplored.

Leptin receptor reactivation restores brain function in early-life Lepr-deficient mice.

Obesity is a chronic disease caused by excessive fat accumulation that impacts the body and brain health. Insufficient leptin or leptin receptor (LepR) is involved in the disease pathogenesis. Leptin is involved with several neurological processes, and it has crucial developmental roles.

Cortical folding correlates to aging and Alzheimer's Disease's cognitive and CSF biomarkers.

This manuscript presents the quantification and correlation of three aspects of Alzheimer's Disease evolution, including structural, biochemical, and cognitive assessments. We aimed to test a novel structural biomarker for neurodegeneration based on a cortical folding model for mammals. Our central hypothesis is that the cortical folding variable, representative of axonal tension in white matter, is an optimal discriminator of pathological aging and correlates with altered loadings in Cerebrospinal Fluid samples and a decline in cognition and memory.

Direct interhemispheric cortical communication via thalamic commissures: a new white matter pathway in the primate brain.

Cortical neurons of eutherian mammals project to the contralateral hemisphere, crossing the midline primarily via the corpus callosum and the anterior, posterior, and hippocampal commissures. We recently reported and named the thalamic commissures (TCs) as an additional interhemispheric axonal fiber pathway connecting the cortex to the contralateral thalamus in the rodent brain. Here, we demonstrate that TCs also exist in primates and characterize the connectivity of these pathways with high-resolution diffusion-weighted MRI, viral axonal tracing, and fMRI.

Social isolation leads to mild social recognition impairment and losses in brain cellularity.

Chronic social stress is a significant risk factor for several neuropsychiatric disorders, mainly major depressive disorder (MDD). In this way, patients with clinical depression may display many symptoms, including disrupted social behavior and anxiety. However, like many other psychiatric diseases, MDD has a very complex etiology and pathophysiology.

Direct interhemispheric cortical communication via thalamic commissures: a new white-matter pathway in the primate brain.

Cortical neurons of eutherian mammals project to the contralateral hemisphere, crossing the midline primarily via the corpus callosum and the anterior, posterior, and hippocampal commissures. We recently reported an additional commissural pathway in rodents, termed the thalamic commissures (TCs), as another interhemispheric axonal fiber pathway that connects cortex to the contralateral thalamus. Here, we demonstrate that TCs also exist in primates and characterize the connectivity of these pathways with high-resolution diffusion-weighted magnetic resonance imaging, viral axonal tracing, and functional MRI.

Heterotopic connectivity of callosal dysgenesis in mice and humans.

The corpus callosum (CC), the largest brain commissure and the primary white matter pathway for interhemispheric cortical connectivity, was traditionally viewed as a predominantly homotopic structure, connecting mirror areas of the cortex. However, new studies verified that most callosal commissural fibers are heterotopic. Recently, we reported that ~75% of the callosal connections in the brains of mice, marmosets, and humans are heterotopic, having an essential role in determining the global properties of brain networks.

The influence of age and sex on the absolute cell numbers of the human brain cerebral cortex.

The human cerebral cortex is one of the most evolved regions of the brain, responsible for most higher-order neural functions. Since nerve cells (together with synapses) are the processing units underlying cortical physiology and morphology, we studied how the human neocortex is composed regarding the number of cells as a function of sex and age. We used the isotropic fractionator for cell quantification of immunocytochemically labeled nuclei from the cerebral cortex donated by 43 cognitively healthy subjects aged 25-87 years old.

Alteration in the number of neuronal and non-neuronal cells in mouse models of obesity.

Obesity is defined as abnormal or excessive fat accumulation that may impair health and is a risk factor for developing other diseases, such as type 2 diabetes and cardiovascular disorder. Obesity is also associated with structural and functional alterations in the brain, and this condition has been shown to increase the risk of Alzheimer's disease. However, while obesity has been associated with neurodegenerative processes, its impact on brain cell composition remains to be determined.

Prefrontal tDCS modulates autonomic responses in COVID-19 inpatients.

Background: maladaptive changes in the autonomic nervous system (ANS) have been observed in short and long-term phases of COVID-19 infection. Identifying effective treatments to modulate autonomic imbalance could be a strategy for preventing and reducing disease severity and induced complications.

Objective: to investigate the efficacy, safety, and feasibility of a single session of bihemispheric prefrontal tDCS on indicators of cardiac autonomic regulation and mood of COVID-19 inpatients.

Reorganization of thalamocortical connections in congenitally blind humans.

Cross-modal plasticity in blind individuals has been reported over the past decades showing that nonvisual information is carried and processed by "visual" brain structures. However, despite multiple efforts, the structural underpinnings of cross-modal plasticity in congenitally blind individuals remain unclear. We mapped thalamocortical connectivity and assessed the integrity of white matter of 10 congenitally blind individuals and 10 sighted controls.

Diagnosis of vascular cognitive impairment: recommendations of the scientific department of cognitive neurology and aging of the Brazilian Academy of Neurology.

Since the publication of the latest recommendations for the diagnosis and treatment of Vascular Dementia by the Brazilian Academy of Neurology in 2011, significant advances on the terminology and diagnostic criteria have been made. This manuscript is the result of a consensus among experts appointed by the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology (2020-2022). We aimed to update practical recommendations for the identification, classification, and diagnosis of Vascular Cognitive Impairment (VCI).

Cerebrospinal fluid irisin and lipoxin A4 are reduced in elderly Brazilian individuals with depression: Insight into shared mechanisms between depression and dementia.

Introduction: Depression is frequent among older adults and is a risk factor for dementia. Identifying molecular links between depression and dementia is necessary to shed light on shared disease mechanisms. Reduced brain-derived neurotrophic factor (BDNF) and neuroinflammation are implicated in the pathophysiology of depression and dementia.

COVID-19 site readiness initiative: Building clinical trial capacity for vaccine efficacy trials in Latin America in response to the pandemic.

According to the World Health Organization, the American region has the highest coronavirus disease-2019 (COVID-19) cases and deaths since the start of the pandemic. This humanitarian tragedy presented the possibility of generating efficacy data from COVID-19 vaccine trials. The race to develop successful vaccines imposed a high demand for trained healthcare personnel and clinical sites where large scale randomized clinical trials could be conducted.

Age-linked suppression of lipoxin A4 associates with cognitive deficits in mice and humans.

Age increases the risk for cognitive impairment and is the single major risk factor for Alzheimer's disease (AD), the most prevalent form of dementia in the elderly. The pathophysiological processes triggered by aging that render the brain vulnerable to dementia involve, at least in part, changes in inflammatory mediators. Here we show that lipoxin A4 (LXA4), a lipid mediator of inflammation resolution known to stimulate endocannabinoid signaling in the brain, is reduced in the aging central nervous system.

The relevance of heterotopic callosal fibers to interhemispheric connectivity of the mammalian brain.

The corpus callosum (CC) is the largest white matter structure and the primary pathway for interhemispheric brain communication. Investigating callosal connectivity is crucial to unraveling the brain's anatomical and functional organization in health and disease. Classical anatomical studies have characterized the bulk of callosal axonal fibers as connecting primarily homotopic cortical areas.

One session of fMRI-Neurofeedback training on motor imagery modulates whole-brain effective connectivity and dynamical complexity.

In the past decade, several studies have shown that Neurofeedback (NFB) by functional magnetic resonance imaging can alter the functional coupling of targeted and non-targeted areas. However, the causal mechanisms underlying these changes remain uncertain. Here, we applied a whole-brain dynamical model to estimate Effective Connectivity (EC) profiles of resting-state data acquired before and immediately after a single-session NFB training for 17 participants who underwent motor imagery NFB training and 16 healthy controls who received sham feedback.

Establishing a Baseline for Human Cortical Folding Morphological Variables: A Multisite Study.

Differences in the way human cerebral cortices fold have been correlated to health, disease, development, and aging. However, to obtain a deeper understanding of the mechanisms that generate such differences, it is useful to derive one's morphometric variables from the first principles. This study explores one such set of variables that arise naturally from a model for universal self-similar cortical folding that was validated on comparative neuroanatomical data.

Using neurofeedback to induce and explore brain plasticity.

A recent study by Sampaio-Baptista and colleagues showed that bidirectionally white matter plasticity can be elicited 24 h after a short regime of neurofeedback (NF) training in healthy individuals. The findings reinforce NF as a tool to induce brain plasticity while highlighting it as a promising intervention for clinical populations.

Corpus callosum dysgenesis causes novel patterns of structural and functional brain connectivity.

Developmental malformations (dysgenesis) of the corpus callosum lead to neurological conditions with a broad range of clinical presentations. Investigating the altered brain connectivity patterns is crucial to understanding both adaptive and maladaptive neuroplasticity in corpus callosum dysgenesis patients. Here, we acquired structural diffusion-weighted and resting-state functional MRI data from a cohort of 11 corpus callosum dysgenesis patients (five with agenesis and six with hypoplasia) and compared their structural and functional connectivity patterns to healthy subjects selected from the Human Connectome Project.

Mild Cognitive Impairment or Attention-Deficit/Hyperactivity Disorder in Older Adults? A Cross Sectional Study.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly prevalent neurodevelopmental condition, which may be associated with life-enduring cognitive dysfunction. It has been hypothesized that age-related cognitive decline may overlap with preexisting deficits in older ADHD patients, leading to increased problems to manage everyday-life activities. This phenomenon may mimic neurodegenerative disorders, in particular Mild Cognitive Impairment (MCI).

Clinical and radiological features of severe acute respiratory syndrome coronavirus 2 meningo-encephalitis.

Background And Purpose: This case illustrates for the first time the clinical and radiological evolution of SARS-CoV-2 meningo-encephalitis.

Methods: A case of a SARS-CoV-2 meningo-encephalitis is reported.

Results: A 65-year-old man with COVID-19 presenting with meningo-encephalitis without respiratory involvement is described.