Brain aging rejuvenation factors in adults with genetic and sporadic neurodegenerative disease.

The largest risk factor for dementia is age. Heterochronic blood exchange studies have uncovered age-related blood factors that demonstrate 'pro-aging' or 'pro-youthful' effects on the mouse brain. The clinical relevance and combined effects of these factors for humans is unclear.

Psychotropic medication usage in sporadic versus genetic behavioral-variant frontotemporal dementia.

Introduction: Psychotropic medication (PM) use in behavioral-variant frontotemporal dementia (bvFTD) is higher than in other dementias. However, no information exists on whether PM use differs between sporadic and genetic bvFTD.

Methods: We analyzed data from sporadic and genetic bvFTD participants with PM prescriptions in the Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects study.

Research priorities to strengthen environmental cleaning in healthcare facilities: the CLEAN Group Consensus.

Environmental cleaning is essential to patient and health worker safety, yet it is a substantially neglected area in terms of knowledge, practice, and capacity-building, especially in resource-limited settings. Public health advocacy, research and investment are urgently needed to develop and implement cost-effective interventions to improve environmental cleanliness and, thus, overall healthcare quality and safety. We outline here the CLEAN Group Consensus exercise yielding twelve urgent research questions, grouped into four thematic areas: standards, system strengthening, behaviour change, and innovation.

Brain inflammation co-localizes highly with tau in mild cognitive impairment due to early-onset Alzheimer's disease.

Brain inflammation, with an increased density of microglia and macrophages, is an important component of Alzheimer's disease and a potential therapeutic target. However, it is incompletely characterized, particularly in patients whose disease begins before the age of 65 years and, thus, have few co-pathologies. Inflammation has been usefully imaged with translocator protein (TSPO) PET, but most inflammation PET tracers cannot image subjects with a low-binder TSPO rs6971 genotype.

Examining Associations Between Smartphone Use and Clinical Severity in Frontotemporal Dementia: Proof-of-Concept Study.

Background: Frontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged <65 years. Several challenges to conducting in-person evaluations in FTLD illustrate an urgent need to develop remote, accessible, and low-burden assessment techniques. Studies of unobtrusive monitoring of at-home computer use in older adults with mild cognitive impairment show that declining function is reflected in reduced computer use; however, associations with smartphone use are unknown.

Implementation of point-of-care molecular testing for respiratory viruses in congregate living settings.

Objective: To implement and evaluate a point-of-care (POC) molecular testing platform for respiratory viruses in congregate living settings (CLS).

Design: Prospective quality improvement study.

Setting: Seven CLS, including three nursing homes and four independent-living facilities.

Anterior insula is more vulnerable than posterior insula to TDP-43 pathology in common dementias and ALS.

Based on the anatomic proximity, connectivity, and functional similarities between the anterior insula and amygdala, we tested the hypothesis that the anterior insula is an important focus in the progression of TDP-43 pathology in LATE-NC. Blinded to clinical and neuropathologic data, phospho-TDP (pTDP) inclusion pathology was assessed in paired anterior and posterior insula samples in 105 autopsied patients with Alzheimer disease, Lewy body disease, LATE-NC and hippocampal sclerosis (HS), amyotrophic lateral sclerosis (ALS), and other conditions. Insular pTDP pathology was present in 34.

Large-scale network analysis of the cerebrospinal fluid proteome identifies molecular signatures of frontotemporal lobar degeneration.

The pathophysiological mechanisms driving disease progression of frontotemporal lobar degeneration (FTLD) and corresponding biomarkers are not fully understood. We leveraged aptamer-based proteomics (> 4,000 proteins) to identify dysregulated communities of co-expressed cerebrospinal fluid proteins in 116 adults carrying autosomal dominant FTLD mutations () compared to 39 noncarrier controls. Network analysis identified 31 protein co-expression modules.

Predictors of SARS-CoV-2 transmission in congregate living settings: a multicenter prospective study.

Background: Older adults residing in congregate living settings (CLS) such as nursing homes and independent living facilities remain at increased risk of morbidity and mortality from coronavirus disease 2019. We performed a prospective multicenter study of consecutive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) exposures to identify predictors of transmission in this setting.

Methods: Consecutive resident SARS-CoV-2 exposures across 17 CLS were prospectively characterized from 1 September 2022 to 1 March 2023, including factors related to environment, source, and exposed resident.

Research Participants' Perspectives on Precision Diagnostics for Alzheimer's Disease.

Background: Understanding research participants' responses to learning Alzheimer's disease (AD) risk information is important to inform clinical implementation of precision diagnostics given rapid advances in disease modifying therapies.

Objective: We assessed participants' perspectives on the meaning of their amyloid positron emission tomography (PET) imaging results for their health, self-efficacy to understand their results, psychological impact of learning their results, experience receiving their results from the clinical team, and interest in genetic testing for AD risk.

Methods: We surveyed individuals who were being clinically evaluated for AD and received PET imaging six weeks after the return of results.

Recruitment of BAG2 to DNAJ-PKAc scaffolds promotes cell survival and resistance to drug-induced apoptosis in fibrolamellar carcinoma.

The DNAJ-PKAc fusion kinase is a defining feature of the adolescent liver cancer fibrolamellar carcinoma (FLC). A single lesion on chromosome 19 generates this mutant kinase by creating a fused gene encoding the chaperonin binding domain of Hsp40 (DNAJ) in frame with the catalytic core of protein kinase A (PKAc). FLC tumors are notoriously resistant to standard chemotherapies.

Effects of High Intensity Ultrasound Stimulation on the Germination Performance of Caper Seeds.

The caper bush has developed different mechanisms to survive in Mediterranean conditions, such as drought tolerance and seed dormancy. Many studies have been carried out to improve the germination of caper seeds, but ultrasound is one of the least studied methodologies in this species. This study aimed to analyze the effects of treatments with an ultrasonic probe processor on the imbibition and germination of caper seeds.

Feasibility and acceptability of remote smartphone cognitive testing in frontotemporal dementia research.

Introduction: Remote smartphone assessments of cognition, speech/language, and motor functioning in frontotemporal dementia (FTD) could enable decentralized clinical trials and improve access to research. We studied the feasibility and acceptability of remote smartphone data collection in FTD research using the ALLFTD Mobile App (ALLFTD-mApp).

Methods: A diagnostically mixed sample of 214 participants with FTD or from familial FTD kindreds (asymptomatic: CDR®+NACC-FTLD = 0 [ = 101]; prodromal: 0.

Plasma inflammation for predicting phenotypic conversion and clinical progression of autosomal dominant frontotemporal lobar degeneration.

Background: Measuring systemic inflammatory markers may improve clinical prognosis and help identify targetable pathways for treatment in patients with autosomal dominant forms of frontotemporal lobar degeneration (FTLD).

Methods: We measured plasma concentrations of IL-6, TNFα and YKL-40 in pathogenic variant carriers () and non-carrier family members enrolled in the ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration consortium. We evaluated associations between baseline plasma inflammation and rate of clinical and neuroimaging changes (linear mixed effects models with standardised (z) outcomes).

Influence of Seed-Covering Layers on Caper Seed Germination.

Caper is a perennial shrub that is widespread in the Mediterranean Basin. Although the fruits contain many seeds, they germinate slowly and with very low percentages, due to their nondeep physiological dormancy. The influence of the testa and endosperm, as well as the effect of applying gibberellic acid (GA) solutions on seed germination to release its dormancy, are reported in this study.

Oncogenic PKA signaling increases c-MYC protein expression through multiple targetable mechanisms.

Genetic alterations that activate protein kinase A (PKA) are found in many tumor types. Yet, their downstream oncogenic signaling mechanisms are poorly understood. We used global phosphoproteomics and kinase activity profiling to map conserved signaling outputs driven by a range of genetic changes that activate PKA in human cancer.

In Alzheimer-prone brain regions, metabolism and risk-gene expression are strongly correlated.

Neuroimaging in the preclinical phase of Alzheimer's disease provides information crucial to early intervention, particularly in people with a high genetic risk. Metabolic network modularity, recently applied to the study of dementia, is increased in Alzheimer's disease patients compared with controls, but network modularity in cognitively unimpaired elderly with various risks of developing Alzheimer's disease needs to be determined. Based on their 5-year cognitive progression, we stratified 117 cognitively normal participants (78.