Basic Science and Pathogenesis.

Background: Sleep dysfunction is commonly seen in Alzheimer's disease (AD) and Progressive Supranuclear Palsy (PSP), potentially worsening these conditions. Investigating early neuropathological changes in human sleep-promoting neurons, which often precede cognitive decline, is crucial for understanding the basis for sleep dysfunction as possible treatments yet remain underexplored. We used postmortem brains of AD and PSP patients to quantify neuronal numbers and tau burden in the intermediate nucleus of the hypothalamus (IntN), VLPO analog, known for its role in sleep maintenance.

Basic Science and Pathogenesis.

Background: Excessive daytime sleepiness is a common and early symptom of Alzheimer's disease (AD). The subcortical wake-promoting neurons in the lateral hypothalamic area, tuberomammillary nucleus (TMN), and locus coeruleus synchronize to maintain wakefulness/arousal. Although significant neuronal decline occurs in wake-promoting regions, the TMN histaminergic neurons remain relatively more intact than orexinergic and nor-adrenergic neurons.

Basic Science and Pathogenesis.

Background: The proteasome plays key roles in synaptic plasticity and memory by regulating protein turnover, quality control, and elimination of oxidized/misfolded proteins. Here, we investigate proteasome function and localization at synapses in Alzheimer's disease (AD) post-mortem brain tissue and in experimental models.

Method: We used primary hippocampal cultures, amyloid-β oligomers (AβO)-injected or transgenic animal models, and human brain tissue to determine brain proteasome function and subcellular localization.

Basic Science and Pathogenesis.

Background: The atherosclerotic plaque in carotid arteries has been associated with dementia. Clinic radiological studies in older adults suggest that the composition of atherosclerotic plaque in the carotid artery can predict vascular dementia (VD) or mixed dementia. The proposed study aims to assess components of atherosclerotic plaques in the carotid arteries, particularly concerning cerebrovascular lesions using racially diverse autopsy samples.

Basic Science and Pathogenesis.

Background: he APOE gene has been identified as a major risk factor for late-onset Alzheimer's disease (AD) and has three most common alleles: ε2, ε3, and ε4. The presence of the ε4 allele confers a dose-dependent increased risk for the disease (odds ratio 12.9 for homozygous individuals and between 3.

Basic Science and Pathogenesis.

Background: Lewy body disease (LBD) is a neurodegenerative condition marked by the accumulation of neuronal alpha-synuclein, leading to both Parkinson's disease and Lewy body dementia. It is regarded as the second most common neurodegenerative disease associated with aging. However, there is limited knowledge of LBD prevalence in the general population, particularly among non-whites.

Basic Science and Pathogenesis.

Background: Clinicopathological studies suggest a role of minor cerebrovascular changes in the cognitive decline of individuals with a low neurodegenerative burden. However, it remains unclear whether small vascular brain lesions can impact cognition in middle aging individuals. Additionally, recent clinicopathological studies have shown that even a low Alzheimer's disease (AD) neuropathological burden can significantly impact neuropsychiatric function.

Basic Science and Pathogenesis.

Background: Individuals meeting neuropathological criteria for Alzheimer's disease (AD) may manifest with atypical clinical syndromes. Past work showed that the neurobiological basis for these differences is related to specific neuronal vulnerabilities for tau pathology. For instance, amnestic cases have a higher burden of neurofibrillary changes in CA1.

Basic Science and Pathogenesis.

Background: The study of dementia and its differences between the sexes is widely investigated, mainly in Alzheimer's disease. However, most studies on dementia are not carried out in a multiethnic population. Here we analyze demographic data, clinical symptoms, and neuropathological characteristics of a large mixed Brazilian sample.

Basic Science and Pathogenesis.

Background: Most research initiatives have emerged from high-income countries (HIC), leaving a gap in understanding the disease's genetic basis in diverse populations like those in Latin American countries (LAC). ReDLat tackles this gap, focusing on LAC's unique genetics and socioeconomic factors to identify specific Alzheimer's Disease (AD) and Frontotemporal Dementia (FTD) risk factors in Mexico, Colombia, Peru, Chile, Argentina, and Brazil.

Method: We employed a comprehensive genetic analysis approach, integrating Whole Genome Sequencing (WGS), Exome Sequencing, and SNP arrays to understand the cohort's unique genetic architecture.

Basic Science and Pathogenesis.

Background: Nitric oxide (NO) is involved in synaptic transmission and cerebral plasticity, playing a role in the memory process. However, in states of brain inflammation, hypoxia, or ischemia, there is induction of inducible nitric oxide synthase (iNOS) expression by astrocytes and pyramidal cells in the brain. Under conditions of chronic activation, there is a decoupling of iNOS dimers, leading to a massive generation of superoxide anion and peroxynitrite, O2.

Basic Science and Pathogenesis.

Background: Alzheimer's Disease(AD) patients experience circadian rhythm disorder. The circadian rhythm is synchronized by a master clock, the suprachiasmatic nucleus(SCN), which is spatially well-conserved but a tiny nucleus in the hypothalamus. Little is known about the molecular and pathological changes that occur in the SCN during AD progression.

Basic Science and Pathogenesis.

Background: Previous studies suggest an association between Alzheimer's disease and carotid artery atherosclerosis. However, the association between atherosclerotic carotid plaque composition and Alzheimer's disease pathology (neuritic plaques and neurofibrillary tangles) has not been explored yet.

Method: Carotid arteries were dissected and the segments with the largest obstruction in the carotid bifurcation, and the common and internal carotid arteries were obtained.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) features stereotypical spread of hyperphosphorylated tau (p-tau) and beta-amyloid. Although other pathological tau posttranslational modifications (PTMs) have been described in AD, a prevalent disease model preconizes that other tau PTMs always coincide with p-tau, making the latter an excellent marker of pathological tau burden. We showed in experimental studies that truncated tau (tr-tau), a pathological tau PTM generated via cleavage by active caspases, is as common as p-tau in neurons at late AD stages; however, only about 40% of tr-tau positive neurons also show p-tau positivity.

Basic Science and Pathogenesis.

Background: Prior research investigating sex and racial differences in amyloid pathology burden has yielded inconsistent findings. We examined the impact of sex and other confounding factors on neuritic plaque burden and cognitive outcomes.

Method: This study included 1,857 individuals, with post-mortem brain tissues, from the Biobank for Aging Studies of the University of São Paulo Medical School, collected from 2004-2023.

Basic Science and Pathogenesis.

Background: Understanding the molecular mechanisms underlying selective neuronal vulnerability is crucial for developing effective treatments for Alzheimer's disease (AD). Our group has shown that RORB/CDH9-positive excitatory neurons in the entorhinal cortex (EC) display selective vulnerability as early as Braak stage (BB) 2. However, not all RORB/CDH9-positive neurons are vulnerable.

Basic Science and Pathogenesis.

Background: Transactive DNA-binding protein 43 (TDP-43) proteinopathy is associated with neurodegeneration, including LATE and linked to cognitive deterioration. While some research suggests a higher prevalence of TDP-43 in women, no differences have been identified among racial groups. Nonetheless, the influence of gender on cognition within the context of TDP-43 remains uncertain.

Clinical Manifestations.

Background: Scientific investigations underscore the cognitive, psychological, and social benefits of cognitive stimulation for aged individuals, yet rigorous long-term studies remain limited.

Method: This abstract outlines the methods and initial participant characteristics of a controlled, randomized clinical trial on cognitive stimulation. A total of 578 aged individuals responded to the study call, with 362 meeting eligibility criteria.

Clinical Manifestations.

Background: This study investigated the effects of cognitive stimulation on older adults over 18 months through a randomized clinical trial with 190 participants divided into Training Group (TG), Active Control Group (ACG), and Passive Control Group (PCG). Initial sociodemographic characterization (Table 1) ensured homogeneity among the groups. The clinical trial design aimed to assess the long-term impacts of multicompartment cognitive stimulation on the cognitive function of older adults in the TG.

Clinical Manifestations.

Background: ApoE has been linked to individual differences in risk and resilience to neurodegeneration in normal aging. The ApoE4 genotype has been associated with an increased risk of developing late-onset Alzheimer's disease (age 65 and older). Within the cognitively healthy population, important differences have been reported in the distribution of ApoE4 alleles and their association with cognitive performance, especially in underrepresented groups.

Clinical Manifestations.

Background: COVID-19 pandemic has brought long-lasting social, emotional, and cognitive consequences. Long COVID is characterized by a myriad of symptoms and complications that persist long after the infection, including cognitive decline and mental health impairment. This study aims to investigate depressive symptoms and cognitive performance stratified by sex and group in adults with and without long COVID.

Clinical Manifestations.

Background: Some older adults with subjective decline (SCD) had a positive amyloid biomarker indicating a preclinical stage of Alzheimer's disease.

Objectives: To assess the accuracy of Delayed Recall of Figure Memory Test (DR-FMT) of Brief Cognitive Screening Battery to predict amyloid status in SCD older adults.

Method: The sample consisted of 45 older adults classified as SCD and 25 as cognitively unimpaired (mean age of 76.

Clinical Manifestations.

Background: Post-COVID19 syndrome is characterized by signs and symptoms that occur within 3 months of the onset of COVID19 acute phase and last at least 2 months. In the past 3 years, cognitive impairment has frequently been associated with COVID19 with descriptions of attentional, executive, memory, and language disorders. Many studies have assessed these cognitive disturbances using online and telephone tests, often in isolated interviews on a cross-sectional design in high-income countries.

SARS-CoV-2 strains and clinical profiles of COVID-19 patients in a Southern Brazil hospital.

Introduction: The COVID-19 pandemic had a widespread global impact and presented numerous challenges. The emergence of SARS-CoV-2 variants has changed transmission rates and immune evasion, possibly impacting the severity. This study aims to investigate the impact of variants on clinical outcomes in southern Brazil.

Embolization of Rectal Arteries for Treating Hemorrhoidal Disease Using a Combination of Microspheres and Microcoils: A Pilot Study.

Purpose: To investigate the feasibility and initial results of superior (SRA) and middle (MRA) rectal artery embolization for patients with symptomatic hemorrhoidal disease.

Materials And Methods: Prospective, single-center cohort that included ten consecutive patients (Goligher classification was II in 70% and III in 30%.) who underwent SRA and MRA embolization using a combination of microspheres and metallic coils, who completed a follow-up period of 12 months.