Public Health.

Background: Subclinical cardiovascular disease (CVD), assessed by high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), is linked to cognitive decline, but the associations in hypertensive adults and the underlying brain pathologies remain unclear. It is also undetermined whether an intensive blood pressure treatment compared to a standard treatment may slow down cognitive decline associated with subclinical CVD.

Method: We conducted a post hoc analysis of the Systolic Blood Pressure Intervention Trial, where older adults with hypertension were randomized to an intensive treatment (systolic blood pressure (SBP) target of < 120 mm Hg) or standard treatment (< 140 mm Hg).

Combination treatment risankizumab and subcutaneous infliximab for refractory Crohn's disease.

We present the case of an 18-year-old male who was diagnosed at age 15 with extensive ileal and colonic Crohn's disease with rectal involvement and associated perianal fistula. The patient received different treatments with biologics withouth achieving response, so we decide to try combination therapy with subcutaneous Infliximab and Risakizumab. The patient showed improvement at second week, achieving both analytical, clinical and endoscopic response .

Public Health.

Background: International collaboration is crucial to the future of research in dementia with Lewy bodies (DLB). Although it is hoped that a single global DLB cohort can be created through combination of data from the many longitudinal studies conducted internationally, a high likelihood of phenotypic heterogeneity may prohibit harmonisation and analysis of datasets. Our primary objective is to determine whether significant heterogeneity is observed in the sociodemographic and clinical characteristics of people with DLB globally.

Public Health.

Background: Approximately 35-40% of new patients at memory clinics are cognitively intact individuals concerned about their dementia risk. The demand for personalized risk profiling and preventive strategies for those at higher dementia risk is in need of innovative infrastructures. However, disclosing dementia risk estimates raises concerns about potential negative emotional impacts.

Public Health.

Background: Women show greater atrophy in medial temporal lobe (MTL) compared to men, irrespective of amyloid burden. We examined whether depressive symptoms, which are more prevalent in women and also linked to MTL atrophy, interact with tau accumulation on MTL atrophy trajectories across 7 years differently among men and women.

Method: We included 71 non-demented ADNI participants with available baseline data on depressive symptoms (Geriatric Depression Scale; GDS), MTL tau accumulation (AV1451 PET BRAAK I/II SUVR [entorhinal and hippocampus]), Centiloids derived from [F]florbetaben and [F]florbetapir and with at least 3 structural MRI visits (mean time = 6.

Public Health.

Background: Adhering to lifestyle-based multimodal interventions to prevent cognitive decline is crucial for their success, but limited evidence exists on determinants of adherence. This gap may stem from inconsistent adherence measurement and reporting across studies. Additionally, uncertainties persist regarding the optimal intervention intensity needed for meaningful cognitive benefits.

Biomarkers.

Background: Limbic-predominant age-related TDP-43 encephalopathy (LATE) can underlie clinical presentations mimicking Alzheimer's disease (AD). Recent imaging-pathological studies have shown that LATE associates with a specific temporo-limbic FDG-PET signature that differs from the typical temporo-parietal pattern of hypometabolism in AD and may be of clinical utility for differential dementia diagnosis. Little is known about the temporal evolution of the respective hypometabolic patterns from early disease stages.

Biomarkers.

Background: The Amyloid Imaging to Prevent Alzheimer's Disease (AMYPAD) Prognostic & Natural History Study (PNHS) is a prospective longitudinal PET cohort of over 1,500 non-demented individuals from 10 parent cohorts across Europe. We provide an overview of ongoing efforts to curate and integrate magnetic resonance imaging (MRI) multimodal images across sites and to extract biologically meaningful information (i.e.

Biomarkers.

Background: Recent developments in physiological and digital biomarkers provide an opportunity to shift the first diagnostic steps to the home-setting, thus allowing earlier detection and treatment of Alzheimer's disease (AD). Blood-based, magnetic resonance imaging, electrophysiological, digital and microbiome biomarkers have shown great promise and call for an evaluation of their accuracy, feasibility and safety in primary care and the community. The aim of PREDICTOM is to develop and test the accuracy of an artificial intelligence (AI) driven screening platform for the prediction and early detection of AD and to extend the clinical pathway to home-based screening using established and novel biomarkers.

Biomarkers.

Background: Amyloid-β (Aβ) pathology affects resting state functional connectivity (RSFC), even in cognitively unimpaired (CU) individuals. However, the impact of such an aberrant RSFC on cognitive decline is yet to be determined. Moreover, most prior research focused on fibrillary Aβ deposition to predict RSFC, while early Aβ dysmetabolism as reflected by cerebrospinal fluid (CSF) concentrations has received less attention.

Biomarkers.

Background: Sleep-wake alterations are common symptoms in Alzheimer's Disease (AD) associated with faster cognitive decline. Noradrenaline dysfunction and neuroinflammation have been proposed as potential driving mechanisms. The ADIS project aims to study the relationship between sleep-wake patterns, immune signatures (peripheral blood cytotoxic lymphocytes), and noradrenergic markers across the AD spectrum.

Biomarkers.

Background: Obstructive sleep apnoea (OSA) is the sleep disorder most frequently found in patients with Alzheimer's disease (AD). The intermittent hypoxia (IH) caused by OSA may participate in AD pathogenesis through increase in oxidative damage and inflammation. We aimed to identify inflammatory and redox genes differentially expressed in the blood from AD patients with severe OSA compared with those with nonsevere OSA.

Biomarkers.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide and the leading cause of dementia in the elderly. New approaches to study AD are still needed to identify and validate blood-based diagnostic biomarkers that could be useful for its early diagnosis. Circulating autoantibodies (AAbs) and their target proteins (autoantigens) are promising candidate biomarkers to aid in AD early diagnosis.

Biomarkers.

Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by early changes in brain structure and cognitive function before the age of onset. This study investigated whether the genetic load for clinical AD and AD pathology predicts AD-related brain and cognitive changes over a 3-year period, targeting the preclinical phase in cognitively unimpaired (CU) middle-aged individuals.

Method: The sample of the study was defined by 429 CU middle-aged participants at risk of AD from the ALFA+ nested cohort with available information on genetics, brain imaging markers and cognitive data [Table 1].

Biomarkers.

Background: Synaptic loss is an eminent feature of tauopathies. The recently developed novel SV2A PET-tracer UCB-J has shown great promise in tracking synaptic loss in tauopathies. However, there have been discrepancies between the in vivo findings and a lack of mechanistic insight.

Biomarkers.

Background: The quantification of neurofilament light chain (NfL) in blood and cerebrospinal fluid (CSF) has proved useful in many contexts, for the diagnosis and prognosis of various neurological disorders. There is, however, a diversity of practices between centers, essentially linked to the context of use (COU), analytical methods, consideration of comorbidities, determination of cut-points or use of interpretation scales. Finally, for the same biochemical profile, the interpretation and reporting of results may differ from one center to another, raising the question of test commutability.

Biomarkers.

Background: Prediction of progression to Alzheimer's Disease Dementia (ADD) at the Mild Cognitive Impairment (MCI) stage is an unmet medical need. Mitochondrial dysfunction in Alzheimer's Disease at the brain and systemic level has been extensively described. Our previous studies showed an altered mtDNA methylation pattern throughout AD progression in human postmortem brains (Blanch et al.

Biomarkers.

Background: Glial fibrillary acidic protein (GFAP) is a marker of cerebral astrogliosis and occasionally elevated in patients with dementia. GFAP in cerebrospinal fluid (CSF), is routinely requested in referrals to neurochemistry laboratories; however, its ability to differentiate dementias and diagnostic capability is unclear. Our aim was to elucidate this, using two large datasets.

Biomarkers.

Background: KLOTHO-VS heterozygosity (KL-VS) has been posited to be a protective factor against age-related disease and cognitive decline, having been associated with increased cortical volumes and brain connectivity, as well as improved cognition in healthy elderly individuals. Conversely, the APOE-ε4 allele is a primary risk factor for the development of Alzheimer's disease (AD), with ε4 carriers more likely to have greater β-amyloid burden, earlier age of AD onset, and accelerated rates of cognitive decline. Relatively few studies have investigated the interaction between these two genetic factors, with those that have presenting conflicting findings.

Biomarkers.

Background: Mild cognitive impairment (MCI), is characterized by cognitive dysfunction not severe enough to affect one's activities of daily living (ADLs)1. Annually, approximately 15-20% adults 65 and older will present with MCI 1. MCI is considered a significant risk factor and a robust predictor for developing dementia.

Tracking Nongenetic Evolution from Primary to Metastatic ccRCC: TRACERx Renal.

Using joint genomic-transcriptomic analysis of 243 samples, we reveal recurrent patterns of nongenetic evolution in ccRCC not exclusively governed by genetic factors, including T-cell depletion, tumor T-cell receptor coevolution, potential cGAS-STING repression, and increased cell proliferation. These patterns can aid clinical management and guide novel treatment approaches.

Biomarkers.

Background: Brain atrophy is a normal part of healthy aging, but it is aggravated by several neurodegenerative diseases. Previous studies have described a large heterogeneity in individual neurodegeneration patterns, but the underlying brain mechanisms are currently not fully understood. From a graph theory-based framework, the estimation of subject-specific focal or multifocal brain atrophy in healthy aging and in the preclinical stage of different neurodegenerative diseases, such as Alzheimer's disease (AD), will help to better understand individual atrophy networks and likely improve prediction of phenotypic heterogeneity in disease trajectories.

Should CAR-T cell therapy be considered a standard of care for patients with refractory diffuse large B-cell lymphoma in second line treatment?

Introduction: CAR-T therapy has transformed the treatment landscape for relapsed/refractory diffuse large B-cell lymphomas (DLBCL).

Areas Covered: This article reviews the existing evidence for using CAR-T therapy as a second-line treatment. Two major phase 3 trials, ZUMA-7 and TRANSFORM, have shown that axi-cel and liso-cel, respectively, offer superior outcomes compared to historical standard chemoimmunotherapy and consolidation with autologous hematopoietic stem cell transplantation (auto-HCT).

Role of a Whole Plant Foods Diet in Breast Cancer Prevention and Survival.

Breast cancer (BC) is one of the leading causes of death and morbidity among women worldwide. Epidemiologic evidence shows that the risk of BC and other chronic diseases decreases as the proportion of whole plant foods increases, while the proportion of animal foods (fish, meat, poultry, eggs, seafood, and dairy products) and non-whole plant foods (e.g.

Biomarkers.

Background: Hippocampal Sclerosis of aging (HS) refers to age-related selective neuronal loss and gliosis in hippocampal cornu ammonis 1 (CA1) and subiculum that is out of proportion to tau pathology in Alzheimer's Disease (AD). HS is related to cognitive decline and memory impairments separately from other neurodegenerative pathologies. To date, in vivo imaging biomarkers of HS of aging are non-existent, and their development would greatly improve diagnosis and prognosis in memory clinics.