Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is characterized by cognitive decline and increased seizure susceptibility due to brain damage and neural disruptions. This study examines the relationship between cognitive deterioration and seizure pathology in hAPP-J20 transgenic Alzheimer's mice, a model known for amyloid plaque deposition and heightened seizure activity.

Method: We observed hAPP-J20 mice aged 8 to 28 weeks using long-term wireless telemetry to assess hippocampal local field potential, sampled at 2 kHz.

Basic Science and Pathogenesis.

Background: This study aimed to explore the association between amyloid-β oligomerization tendency (OAβ) in plasma and cognitive performance in patients with Alzheimer's disease (AD) and further determine whether plasma OAβ could predict the outcomes of patients with mild cognitive impairment (MCI).

Method: The plasma from 727 subjects in a case registry was tested; these subjects included 286 AD patients, 260 MCI patients and 181 normal controls. The multimer detection system (MDS) was used to measure the plasma oligomeric form of Aβ levels.

Basic Science and Pathogenesis.

Background: Although the rate of Alzheimer's disease (AD) in African-ancestry (AA) Americans is higher than that of persons from European-ancestry (EA) populations, AA participants have been underrepresented in AD neuropathological studies.

Method: Utilizing the AD Research Centers (ADRC) infrastructure, we obtained AA donor pre-frontal cortex (PFC) tissue from brain repositories of 12 ADRC and generated bulk RNA sequencing (RNA-seq) data for 179 samples that met QC and inclusion criteria. Previously generated PFC RNAseq data were obtained for 28 additional AA donors from the Columbia University ADRC.

Clinical Manifestations.

Background: Alzheimer's disease and related dementias (ADRD) disproportionately affect Latinos compared to non-Latino whites. Leveraging the non-monolithic structure of Latin America, which represents a large variability in social determinants of health (SDoH) and high levels of genetic admixture, we aimed to determine contributors to ADRD disparities within Latinos, focusing on genetic ancestry and SDoH.

Method: Community-dwelling participants aged 65 and older (n = 4000) from Cuba, Dominican Republic, Mexico, and Peru completed the 10/66 protocol assessments, including sociodemographic and risk factors questionnaire, neurological exam, cognitive assessment, and blood draw.

Basic Science and Pathogenesis.

Background: The "Recruitment and Retention for Alzheimer's Disease Diversity Genetic Cohorts in the ADSP (READD-ADSP)" is developing a resource to expand ancestral diversity in Alzheimer disease (AD) studies to dissect the genetic architecture of AD across different populations. In addition to US sites, READD-ADSP includes four US sites and nine countries in sub-Saharan Africa through the Africa Dementia Consortium (AfDC). The overall goal of READD-ADSP is to identify genetically driven targets in diverse groups including African Americans and Hispanic/Latinos in US, and Africans.

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: The Clinical Dementia Rating Sum of Boxes (CDR-SB) is a widely used measurement score to stage dementia severity; it has become one of the most common outcome measurements in Alzheimer's Disease (AD) research. The CDR-SB requires an informant to provide information to stage a patient's dementia severity. The effect of the informant's characteristics including sex and relationship with patients on the CDR-SB is unknown.

Clinical Manifestations.

Background: Cognitive assessments are essential for the diagnosis of mild cognitive impairment (MCI) and dementia. However, existing tests are mostly developed in English-speaking cohorts. Hence, their application in multilingual populations will need translation which may affect their test psychometrics.

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: Early-Onset Alzheimer's Disease (EOAD) is a rare condition that affects only 5% of patients with Alzheimer's Disease (AD). At present, only basic information is known about the impact of AD risk variants on EOAD, and the effects of more subtle genetic contributions to cognitive decline have yet to be investigated. Genetic variants for brain derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT) have both been implicated in cognitive change (Fiocco et al.

Clinical Manifestations.

Background: Over 13,000 individuals from both domestic and African sites will be collected for the READD-ADSP study. Adjudicating this number of individuals is challenging, so we evaluated knowledge-based decision tree algorithms to predict clinical diagnoses using nationally representative norms and standard cut-offs. Additional models were constructed using culturally adjusted cut-offs, domain average cut-offs, and exclusion of the Trail Making Test (TMT) which performed poorly.

Metabolic Characterization of Cerebrospinal Fluid for Patients With Autoimmune Encephalitis: A Preliminary Study.

Background: Metabolomics offers promise in uncovering potential biomarkers and understanding the pathophysiology of autoimmune encephalitis (AE), which is a cluster of disorders with the host immune system targeting self-antigens expressed in the central nervous system (CNS). In this research, our objective was to explore metabolic characterization in cerebrospinal fluid (CSF) from individuals with AE, aiming to shed light on the pathophysiology of AE.

Methods: A targeted approach was applied using an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system to study CSF metabolites in patients with AE (n = 18), and control subjects without neurological diseases (n = 17).

The Effect of APOE ε4 on Alzheimer's Disease Fluid Biomarkers: A Cross-Sectional Study Based on the COAST.

Aims: To analyze the effect of APOE ε4 on fluid biomarkers and the correlations between blood molecules and CSF biomarkers in AD patients.

Methods: This study enrolled 575 AD patients, 131 patients with non-AD dementia, and 112 cognitively normal (CN) participants, and AD patients were divided into APOE ε4 carriers and non-carriers. Cerebrospinal fluid (CSF) biomarkers and blood-derived biomolecules were compared between AD and CN groups, between non-AD dementia and CN groups, as well as within APOE ε4 subgroups of AD patients.

Post-acute sequela of COVID-19 infection in individuals with multiple sclerosis.

Background: Many common symptoms in post-acute sequelae following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) overlap with those of multiple sclerosis (MS). We examined symptoms and performance of the PASC score, developed in the general population, in MS based on infection history.

Methods: We surveyed North American Research Committee on Multiple Sclerosis (NARCOMS) registry participants regarding infections and categorized participants based on infection history.

Effects of sex on imaging-based intravenous thrombolysis for ischaemic stroke with unknown onset time: a pooled analysis of clinical trials.

Introduction: The effects of imaging-based intravenous thrombolysis on outcomes based on patient sex remain unclear. We aimed to investigate whether outcomes among patients with stroke with an unknown onset time and treated with imaging-based intravenous thrombolysis are influenced by their sex.

Patients And Methods: This study was a pooled analysis of individual patient-level data acquired from the Evaluation of unknown Onset Stroke thrombolysis trials.

Association between Atopic Dermatitis and Dementia: Evidence from Systematic Review, Meta-analysis, and Mendelian Randomization.

Recent cohort studies suggest a potential association between atopic dermatitis and dementia, though the evidence remains conflicting. This study aims to elucidate the association between atopic dermatitis and dementia employing systematic review, meta-analysis, and Mendelian randomization (MR). A comprehensive search was performed to select eligible cohort studies using Medline, Embase, Scopus, ScienceDirect, and the Web of Science database.

Imaging biomarker associated with early neurological deterioration in isolated pontine infarction.

Objective: To investigate the association between cerebral small vessel disease burden, along with its individual imaging features, as well as other imaging features and early neurological deterioration in isolated pontine infarction.

Methods: 107 patients with acute isolated pontine infarcts, within 24 h of symptom onset, were retrospectively analyzed. The mean age of the participants was 67 years.

Emerging Alzheimer's disease treatment paradigms: A late-stage clinical trial review.

Introduction: Without disease-modifying interventions, Medicare and Medicaid spending on Alzheimer's disease (AD) management is expected to reach 637 billion USD annually by 2050. The recent advent of promising AD therapies after decades of a near-total failure rate in clinical trials suggests that more disease-modifying therapies are on the horizon. In this review, we assess the late-stage pipeline of disease-modifying candidates for AD and offer a novel classification of intervention candidates by treatment paradigms-groups of candidates that share an underlying biological mechanism of action and general disease target.

Relationship between physical activity and biomarkers of pathology and neuroinflammation in preclinical autosomal-dominant Alzheimer's disease.

Objective: Physical activity (PA) has been linked to reduced Alzheimer's disease (AD) risk. However, less is known about its effects in the AD preclinical stage. We aimed to investigate whether greater PA was associated with lower plasma biomarkers of AD pathology, neural injury, reactive astrocytes, and better cognition in individuals with autosomal-dominant AD due to the presenilin-1 E280A mutation who are virtually guaranteed to develop dementia.

Designing and implementing the IDEAL Study: A randomized clinical trial of genotype disclosure for late-onset Alzheimer's disease in an urban Latino population.

Introduction: The (IDEAL) Study is a randomized clinical trial investigating the psychosocial, behavioral, and cognitive impacts of apolipoprotein E () genotype disclosure for late-onset Alzheimer's disease (AD) among Latinos.

Methods: We used address-based sampling to recruit English- and Spanish-speaking Latinos aged 40-64 living in northern Manhattan for a community-based Baseline Survey about their knowledge and opinions about AD. Participants eligible for the clinical trial were invited to complete an Introductory Session, including AD and genetics education and informed consent, before undergoing genotyping for .

Unraveling the causal impact of smoking and its DNA methylation signatures on cardiovascular disease: Mendelian randomization and colocalization analysis.

Background: To explore the mechanisms linking smoking to cardiovascular diseases (CVDs) from an epigenetic perspective.

Methods: Mendelian Randomization (MR) analysis was performed to assess the causal effects of smoking behavior and DNA methylation levels at smoking-related CpG sites on nine CVDs, including aortic aneurysm, atrial fibrillation, coronary atherosclerosis, coronary heart disease, heart failure, intracerebral hemorrhage, ischemic stroke, myocardial infarction, subarachnoid hemorrhage. Colocalization analysis was used to further identify key smoking-related CpG sites from the MR causal estimates.

Cerebrospinal fluid β2-microglobulin promotes the tau pathology through microglia-astrocyte communication in Alzheimer's disease.

Background: Cerebrospinal fluid (CSF) β2-microglobulin (β2M) has been demonstrated as an important factor in β-amyloid (Aβ) neurotoxicity and a potential target for Alzheimer's disease (AD). However, more investigation is required to ascertain the relationship between β2M and glial activities in AD pathogenesis.

Methods: In this study, 211 participants from the Alzheimer's disease Neuroimaging Initiative (ADNI) with CSF and Plasma β2M, CSF glial fibrillary acidic protein (GFAP), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), Aβ, phosphorylated-tau (P-tau) and total tau (T-tau) were divided into four groups, stage 0, 1, 2, and suspected non-AD pathology (SNAP) based on the National Institute on Aging- Alzheimer's Association (NIA-AA) criteria.

Seizure aggravation by ampicillin/sulbactam in an elderly patient with status epilepticus.

Background: Ampicillin/sulbactam (ABPC/ SBT) is one of the most common β-lactam antibiotics for patients with status epilepticus complicated with aspiration pneumonia. It is known that β-lactam antibiotics such as penicillin aggravate epileptic seizures or status epilepticus. Here, we investigated whether ABPC/SBT aggravates seizures using electroencephalography (EEG) monitoring.

Vertebral artery dissection in a patient with migraine treated with calcitonin gene-related peptide monoclonal antibody: a case report and FAERS database analysis.

Background: Migraine is associated with cervical artery dissection (CeAD). Calcitonin gene-related peptide (CGRP) is a multifunctional neuropeptide with vasodilatory effects. The use of anti-CGRP monoclonal antibodies (CGRP mAb) may affect cerebrovascular disease risk; however, no reports have associated CGRP mAb with CeAD.