Biomarkers.

Background: The interaction between Alzheimer's pathology and cerebral amyloid angiopathy (CAA), a common cerebral small vessel disease, plays a crucial role in cognitive impairment development in older adults. Recent studies suggest that increased blood pressure (BP) variability may affect subclinical vascular disease and cognitive decline. However, it is currently unknown whether a particular BP profile is linked to hippocampal subfield volumes, which are a significant feature of cognitive decline in neurodegenerative diseases.

Biomarkers.

Background: Highly specific ATN plasma biomarker assays for neurodegenerative diseases have been developed, but their associations with cognition vary in different populations. Kidney disease, common in diabetes, may decrease the predictive precision of those biomarkers. The aim of this study was to characterize for the first time the relationships between plasma ATN biomarkers and cognitive function in adults with T1D.

Biomarkers.

Background: Diagnosing sporadic early-onset AD (EOAD, age-at-onset<65) is challenging: in the multi-center Longitudinal Early-onset Alzheimer's Disease Study, ∼25% of patients with clinically diagnosed EOAD are amyloid-PET-negative. Here we used FDG-PET to characterize the heterogeneity of hypometabolic profiles in these patients and better identify underlying etiologies.

Method: Seventy-four amyloid-PET-negative patients with clinical diagnosis of sporadic EOAD (MCI or mild dementia stage) underwent FDG-PET.

Biomarkers.

Background: Individuals from diverse racial and ethnic groups are severely underrepresented in AD trials in part due to disproportionate biomarker ineligibility. Evidence from recent studies support plasma phosphorylated tau (P-tau217) as an early marker for brain Aβ pathology and a reliable marker in predicting elevated brain amyloid PET in cognitively unimpaired adults. We examined the relationship between P-tau217 and florbetapir PET standard uptake value ratios (SUVR) by self-reported racial and ethnic groups in preclinical AD studies.

Biomarkers.

Background: Data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) trial (NCT02008357), including cognitively unimpaired participants with brain amyloid pathology on florbetapir F 18, demonstrates that levels of plasma P-tau217, as detected by an electrochemiluminescence (ECL) immunoassay, is strong predictor of elevated cerebral amyloid on florbetapir PET in cognitively unimpaired individuals. Here we compare plasma P-tau217 measures over 12 weeks using a P-tau217 ECL immunoassay.

Method: A4 trial placebo-group participants who had their first baseline and first post-baseline plasma P-tau217 samples collected within 175 days of each other were included in these analyses.

Biomarkers.

Background: Cognitive dysfunction is more common in individuals with type 1 diabetes (T1D) compared to the general population. Blood-based biomarkers are accurate in identifying early signs of neurodegeneration. However, studies using these biomarkers in T1D are lacking.

Biomarkers.

Background: Bilingualism can stimulate brain plasticity (Jafari et al. Ann N Y Acad Sci. 2021;1505(1):8-22) and is also associated with better executive function (Grundy.

TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids.

Novel therapeutic strategies are needed to improve the efficacy of chimeric antigen receptor (CAR) T cells as a treatment of solid tumors. Multiple tumor microenvironmental factors are thought to contribute to resistance to CAR T-cell therapy in solid tumors, and appropriate model systems to identify and examine these factors using clinically relevant biospecimens are limited. In this study, we examined the activity of B7-H3-directed CAR T cells (B7-H3.

Biomarkers.

Background: Estimating the time course of locus coeruleus integrity changes is important for a better understanding of the pathophysiological cascade and for identifying the optimal window of opportunity for prevention trials. We used samples iterative local approximation (SILA) to determine the individual estimated time of onset of low LC integrity and related this to early cortical tau deposition and cognitive decline.

Methods: 101 individuals from the Harvard Aging Brain Study+ with longitudinal 3T MRI-LC imaging, 18F-Flortaucipir (FTP)-PET imaging (n=92 with longitudinal data), longitudinal cognitive assessments and baseline PiB-PET imaging were included (mean age: 69.

Biomarkers.

Background: There is an urgent need for neuropsychological screening tests that are easily deployed and reliable. We have developed a digital neuropsychological screening protocol that is administered on a tablet, automatically scored using artificial intelligence, and requires approximately 10 minutes to administer. This tablet-administered protocol assesses the requisite neurocognitive constructs associated with emergent neurodegenerative illness METHOD: The digital protocol was administered to 77 ambulatory care/ memory clinic patients (Table 1).

Biomarkers.

Background: Digital health research on Alzheimer's disease (AD) points to automated speech and language analysis (ASLA) as a globally scalable approach for diagnosis and monitoring. However, most studies target uninterpretable features in Anglophone samples, casting doubts on the approach's clinical utility and cross-linguistic validity. The present study was designed to tackle both issues.

Biomarkers.

Background: White matter lesions (WMLs) are common with aging and are prevalent in AD, but the underlying physiology as well as associations with conventional vascular risk factors are not yet fully understood. In this study, we investigated the relationship between vascular risk factors and microvascular physiology (i.e.

Biomarkers.

Background: Tau-PET imaging allows in-vivo detection of neurofibrillary tangles. One tau-PET tracer (i.e.

Biomarkers.

Background: To validate the index of diffusivity along the perivascular space (ALPS index) as a biomarker for vascular cognitive impairment and dementia (VCID).

Method: The participants and MRI data used in this study were acquired as part of the MarkVCID consortium, which consisted of seven sites. A total of 578 participants (72.

Biomarkers.

Background: Studying brain reserve - the brain's resilience to age-related changes or damage - is crucial for understanding protective mechanisms against cognitive decline. The cerebellum may be a key region in brain reserve, but it has been historically understudied. This investigation delves into this critical area within the largest aging multi-cohort to date.

Cardiovascular MRI-derived Right Atrial Strain for Improved Risk Stratification in Patients with Severe Aortic Stenosis.

Purpose To assess the prognostic implications of cardiac MRI-derived imaging markers in individuals with severe aortic stenosis (AS). Materials and Methods This prospective study (German Clinical Trials Register, DRKS00024479) enrolled individuals with severe AS who underwent cardiac MRI before transcatheter aortic valve replacement (TAVR) from January 2017 to March 2022. Image analyses included myocardial volumes, cardiac MRI feature tracking-derived left atrial (LA) and right atrial (RA) as well as left ventricular (LV) and right ventricular (RV) strain, myocardial T1 mapping, and late gadolinium enhancement analyses.

We Should Perform a Systematic Evaluation of the Placenta.

Despite its critical importance, the placenta receives substantially less attention during obstetric ultrasound examinations compared to the fetus. The evaluation of the placenta is typically limited to determining its location within the uterus, particularly its relationship to the cervix. Abnormal placenta findings are the result of gross anomalies identified by chance during obstetric examinations, rather than from a systematic evaluation.

Biomarkers.

Background: Sleep disturbances are common in Alzheimer's disease (AD) and occur at early stages. Hyperexcitability also arises during sleep and can lead to epileptiform activity and seizures that impact memory consolidation. The underlying mechanisms of sleep disturbances and hyperexcitability in AD pathology remain unclear but are likely associated with changes in brain networks and altered functional connectivity (FC).

Biomarkers.

Background: A novel method using diffusion-weighted imaging (DWI) allows for assessing microstructural injury in the gray matter by measuring cortical mean diffusivity (cMD). Previous studies have shown that altered cMD is related to amyloid (Aβ) cross-sectionally and can predict longitudinal cognitive decline and clinical progression, suggesting utility in clinical trials. However, the longitudinal associations between these measures are unknown.

Biomarkers.

Background: Alzheimer disease (AD) related cognitive decline occurs at relatively young ages in individuals with Down syndrome (DS, early-mid 50s) and in those with autosomal dominant mutations (ADAD, 40-50s). Both groups show similar patterns of amyloid accumulation. We examined if brain volumes are similarly affected by AD pathology in individuals with DS and ADAD.

Biomarkers.

Background: Cortical excitability is elevated in Alzheimer's disease (AD). Transcranial magnetic stimulation-evoked responses on electromyography (EMG) and electroencephalography (EEG) have captured this increased excitability in motor brain regions. However, it is not yet known if increased excitability is also present in the parietal lobe or the extent to which excitability is related to cognition.

Biomarkers.

Background: Cognitive resilience (CR) refers to the continuum from worse to better-than-expected cognition, given the degree of neuropathology. Understanding mechanisms underlying CR could inform discovery of novel targets for dementia prevention; however, specific metabolic pathways underlying CR are yet to be elucidated.

Methods: Our study included 484 deceased participants (mean age at death =91 years, 70.

Biomarkers.

Background: Neuron-derived extracellular vesicles (NDEVs) are a valuable resource for understanding brain conditions and discovering neurodegenerative diseases biomarkers, notably Alzheimer's disease (AD). Recent interest focuses on capturing neuron-specific EVs from patient-derived samples, characterizing their contents as a pathological reflection of the central nervous system (CNS). Our recent study identified ATPase Na/K Transporting Subunit Alpha 3 (ATP1A3) as a prevalent neuron-specific EV marker specifically expressed in brains.

Biomarkers.

Background: The ability to accurately discern memory function (i.e., metamemory) decreases with age and is further diminished in Alzheimer's disease (AD).

Serum Phosphorus and Hypophosphatemia During Therapy of Diabetic Ketoacidosis in Children: Single-Center, Retrospective Cohort 2016-2022.

Objectives: To assess factors associated with serum phosphorus (P) and hypophosphatemia in children with type 1 diabetes mellitus (T1DM) treated for diabetic ketoacidosis (DKA).

Design: Retrospective cohort.

Setting: Community-based PICU in a university-affiliated hospital.