Rates of cortical thinning in Alzheimer's disease signature regions associate with vascular burden but not with β-amyloid status in cognitively normal adults at age 70.

Background: Consistent patterns of reduced cortical thickness have been identified in early Alzheimer's disease (AD). However, the pathological factors that influence rates of cortical thinning within these AD signature regions remain unclear.

Methods: Participants were from the Insight 46 substudy of the MRC National Survey of Health and Development (NSHD; 1946 British birth cohort), a prospective longitudinal cohort study.

Neuroimaging, clinical and life course correlates of normal-appearing white matter integrity in 70-year-olds.

We investigate associations between normal-appearing white matter microstructural integrity in cognitively normal ∼70-year-olds and concurrently measured brain health and cognition, demographics, genetics and life course cardiovascular health. Participants born in the same week in March 1946 (British 1946 birth cohort) underwent PET-MRI around age 70. Mean standardized normal-appearing white matter integrity metrics (fractional anisotropy, mean diffusivity, neurite density index and orientation dispersion index) were derived from diffusion MRI.

Operationalizing the centiloid scale for [F]florbetapir PET studies on PET/MRI.

Introduction: The Centiloid scale aims to harmonize amyloid beta (Aβ) positron emission tomography (PET) measures across different analysis methods. As Centiloids were created using PET/computerized tomography (CT) data and are influenced by scanner differences, we investigated the Centiloid transformation with data from Insight 46 acquired with PET/magnetic resonanceimaging (MRI).

Methods: We transformed standardized uptake value ratios (SUVRs) from 432 florbetapir PET/MRI scans processed using whole cerebellum (WC) and white matter (WM) references, with and without partial volume correction.

Adulthood cognitive trajectories over 26 years and brain health at 70 years of age: findings from the 1946 British Birth Cohort.

Few studies can address how adulthood cognitive trajectories relate to brain health in 70-year-olds. Participants (n = 468, 49% female) from the 1946 British birth cohort underwent 18F-Florbetapir PET/MRI. Cognitive function was measured in childhood (age 8 years) and across adulthood (ages 43, 53, 60-64 and 69 years) and was examined in relation to brain health markers of β-amyloid (Aβ) status, whole brain and hippocampal volume, and white matter hyperintensity volume (WMHV).

Management of Malignant Bowel Obstruction: An Innovative Proactive Outpatient Nurse-Led Model of Care for Patients With Advanced Gynecologic Cancer.

Background: Malignant bowel obstruction (MBO) in patients with advanced gynecologic cancer (GyCa) can negatively impact clinical outcomes and quality of life. Oncology nurses can support these patients with adequate tools/processes.

Problem: Patients with GyCa with/at risk of MBO endure frequent emergency or hospital admissions, impacting patient care.

Life course, genetic, and neuropathological associations with brain age in the 1946 British Birth Cohort: a population-based study.

Background: A neuroimaging-based biomarker termed the brain age is thought to reflect variability in the brain's ageing process and predict longevity. Using Insight 46, a unique narrow-age birth cohort, we aimed to examine potential drivers and correlates of brain age.

Methods: Participants, born in a single week in 1946 in mainland Britain, have had 24 prospective waves of data collection to date, including MRI and amyloid PET imaging at approximately 70 years old.

The psychosocial needs of patients who have chronic kidney disease without kidney replacement therapy: a thematic synthesis of seven qualitative studies.

Background: Limited quantitative data suggests that patients who have chronic kidney disease without kidney replacement therapy (CKD without KRT) may present with psychosocial needs just as patients who have acute kidney injury and are treated by dialysis (AKI stage 3D) do. This systematic review aims to synthesise qualitative research on patients' experiences of CKD without KRT to provide further insight into patients' experience of the healthcare they receive and simultaneously, their psychosocial needs, to inform the development of appropriate psychological interventions.

Methods: The review followed ENTREQ guidelines.

Dementia Prevention Research Clinic: a longitudinal study investigating factors influencing the development of Alzheimer's disease in Aotearoa, New Zealand.

Aotearoa New Zealand's population is ageing. Increasing life expectancy is accompanied by increases in prevalence of Alzheimer's Disease (AD) and ageing-related disorders. The multicentre Dementia Prevention Research Clinic longitudinal study aims to improve understanding of AD and dementia in Aotearoa, in order to develop interventions that delay or prevent progression to dementia.

Associations of β-Amyloid and Vascular Burden With Rates of Neurodegeneration in Cognitively Normal Members of the 1946 British Birth Cohort.

Background And Objectives: The goals of this work were to quantify the independent and interactive associations of β-amyloid (Aβ) and white matter hyperintensity volume (WMHV), a marker of presumed cerebrovascular disease (CVD), with rates of neurodegeneration and to examine the contributions of ε4 and vascular risk measured at different stages of adulthood in cognitively normal members of the 1946 British Birth Cohort.

Methods: Participants underwent brain MRI and florbetapir-Aβ PET as part of Insight 46, an observational population-based study. Changes in whole-brain, ventricular, and hippocampal volume were directly measured from baseline and repeat volumetric T1 MRI with the boundary shift integral.

Dissociable effects of -ε4 and β-amyloid pathology on visual working memory.

Although -ε4 carriers are at significantly higher risk of developing Alzheimer's disease than non-carriers, controversial evidence suggests that -ε4 might confer some advantages, explaining the survival of this gene (antagonistic pleiotropy). In a population-based cohort born in one week in 1946 (assessed aged 69-71), we assessed differential effects of -ε4 and β-amyloid pathology (quantified using F-Florbetapir-PET) on visual working memory (object-location binding). In 398 cognitively normal participants, -ε4 and β-amyloid had opposing effects on object identification, predicting better and poorer recall respectively.

Mild Parkinsonian Signs: A Systematic Review of Clinical, Imaging, and Pathological Associations.

Mild parkinsonian signs (MPS) have been widely studied during the past 3 decades and proposed as a risk marker for neurodegenerative disease. This systematic review explores the epidemiology, clinical and prognostic associations, radiological features, and pathological findings associated with MPS in older adults free from neurodegenerative disease. We find that MPS as currently defined are strongly associated with increasing age and increased risk of development of Parkinson's disease (PD), all-cause dementia, disability, and death.

Socioeconomic position links circulatory microbiota differences with biological age.

Imbalanced nutrition is associated with accelerated ageing, possibly mediated by microbiota. An analysis of the circulatory microbiota obtained from the leukocytes of participants in the MRC Twenty-07 general population cohort was performed. We now report that in this cohort, the most biologically aged exhibit a significantly higher abundance of circulatory pathogenic bacteria, including Neisseria, Rothia and Porphyromonas, while those less biologically aged possess more circulatory salutogenic (defined as being supportive of human health and wellbeing) bacteria, including Lactobacillus, Lachnospiraceae UCG-004 and Kocuria.

Subjective cognitive complaints at age 70: associations with amyloid and mental health.

Objective: To investigate subjective cognitive decline (SCD) in relation to β-amyloid pathology and to test for associations with anxiety, depression, objective cognition and family history of dementia in the Insight 46 study.

Methods: Cognitively unimpaired ~70-year-old participants, all born in the same week in 1946 (n=460, 49% female, 18% amyloid-positive), underwent assessments including the SCD-Questionnaire (MyCog). MyCog scores were evaluated with respect to F-Florbetapir-PET amyloid status (positive/negative).

Investigating the relationship between BMI across adulthood and late life brain pathologies.

Background: In view of reported associations between high adiposity, particularly in midlife and late-life dementia risk, we aimed to determine associations between body mass index (BMI), and BMI changes across adulthood and brain structure and pathology at age 69-71 years.

Methods: Four hundred sixty-five dementia-free participants from Insight 46, a sub-study of the British 1946 birth cohort, who had cross-sectional T1/FLAIR volumetric MRI, and florbetapir amyloid-PET imaging at age 69-71 years, were included in analyses. We quantified white matter hyperintensity volume (WMHV) using T1 and FLAIR 3D-MRI; β-amyloid (Aβ) positivity/negativity using a SUVR approach; and whole brain (WBV) and hippocampal volumes (HV) using 3D T1-MRI.

A population-based study of head injury, cognitive function and pathological markers.

Objective: To assess associations between head injury (HI) with loss of consciousness (LOC), ageing and markers of later-life cerebral pathology; and to explore whether those effects may help explain subtle cognitive deficits in dementia-free individuals.

Methods: Participants (n = 502, age = 69-71) from the 1946 British Birth Cohort underwent cognitive testing (subtests of Preclinical Alzheimer Cognitive Composite), F-florbetapir Aβ-PET and MR imaging. Measures include Aβ-PET status, brain, hippocampal and white matter hyperintensity (WMH) volumes, normal appearing white matter (NAWM) microstructure, Alzheimer's disease (AD)-related cortical thickness, and serum neurofilament light chain (NFL).

Visuomotor integration deficits are common to familial and sporadic preclinical Alzheimer's disease.

We investigated whether subtle visuomotor deficits were detectable in familial and sporadic preclinical Alzheimer's disease. A circle-tracing task-with direct and indirect visual feedback, and dual-task subtraction-was completed by 31 individuals at 50% risk of familial Alzheimer's disease (19 presymptomatic mutation carriers; 12 non-carriers) and 390 cognitively normal older adults (members of the British 1946 Birth Cohort, all born during the same week; age range at assessment = 69-71 years), who also underwent β-amyloid-PET/MRI to derive amyloid status (positive/negative), whole-brain volume and white matter hyperintensity volume. We compared preclinical Alzheimer's groups against controls cross-sectionally (mutation carriers versus non-carriers; amyloid-positive versus amyloid-negative) on speed and accuracy of circle-tracing and subtraction.

Concordance of CSF measures of Alzheimer's pathology with amyloid PET status in a preclinical cohort: A comparison of Lumipulse and established immunoassays.

Introduction: We assessed the concordance of cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau measured on the fully automated Lumipulse platform with pre-symptomatic Alzheimer's disease (AD) pathology on amyloid positron emission tomography (PET).

Methods: In 72 individuals from the Insight 46 study, CSF Aβ40, Aβ42, total tau (t-tau), and phosphorylated tau at site 181 (p-tau181) were measured using Lumipulse, INNOTEST, and Meso Scale Discovery (MSD) assays and inter-platform Pearson correlations derived. Lumipulse Aβ42 measures were adjusted to incorporate standardization to certified reference materials.

Population-based blood screening for preclinical Alzheimer's disease in a British birth cohort at age 70.

Alzheimer's disease has a preclinical stage when cerebral amyloid-β deposition occurs before symptoms emerge, and when amyloid-β-targeted therapies may have maximum benefits. Existing amyloid-β status measurement techniques, including amyloid PET and CSF testing, are difficult to deploy at scale, so blood biomarkers are increasingly considered for screening. We compared three different blood-based techniques-liquid chromatography-mass spectrometry measures of plasma amyloid-β, and single molecule array (Simoa) measures of plasma amyloid-β and phospho-tau181-to detect cortical 18F-florbetapir amyloid PET positivity (defined as a standardized uptake value ratio of >0.

Identifying Differing Intracellular Cargo Release Mechanisms by Monitoring Drug Delivery from MOFs in Real Time.

Metal-organic frameworks (MOFs) have been proposed as biocompatible candidates for the targeted intracellular delivery of chemotherapeutic payloads, but the site of drug loading and subsequent effect on intracellular release is often overlooked. Here, we analyze doxorubicin delivery to cancer cells by MIL-101(Cr) and UiO-66 in real time. Having experimentally and computationally verified that doxorubicin is pore loaded in MIL-101(Cr) and surface loaded on UiO-66, different time-dependent cytotoxicity profiles are observed by real-time cell analysis and confocal microscopy.

Concordance of CSF measures of Alzheimer's pathology with amyloid PET status in a preclinical cohort: A comparison of Lumipulse and established immunoassays.

Introduction: We assessed the concordance of cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau measured on the fully automated Lumipulse platform with pre-symptomatic Alzheimer's disease (AD) pathology on amyloid positron emission tomography (PET).

Methods: In 72 individuals from the Insight 46 study, CSF Aβ40, Aβ42, total tau (t-tau), and phosphorylated tau at site 181 (p-tau181) were measured using Lumipulse, INNOTEST, and Meso Scale Discovery (MSD) assays, and inter-platform Pearson correlations were derived. Logistic regressions and receiver-operating characteristic analysis generated CSF cut-points optimizing concordance with F-florbetapir amyloid PET status (n = 63).

Klotho, Aging, and the Failing Kidney.

Klotho has been recognized as a gene involved in the aging process in mammals for over 30 years, where it regulates phosphate homeostasis and the activity of members of the fibroblast growth factor (FGF) family. The α-Klotho protein is the receptor for Fibroblast Growth Factor-23 (FGF23), regulating phosphate homeostasis and vitamin D metabolism. Phosphate toxicity is a hallmark of mammalian aging and correlates with diminution of Klotho levels with increasing age.

Increased variability in reaction time is associated with amyloid beta pathology at age 70.

Introduction: We investigated whether life-course factors and neuroimaging biomarkers of Alzheimer's disease pathology predict reaction time (RT) performance in older adults.

Methods: Insight 46 study participants, all born in the same week in 1946 (n = 501; ages at assessment = 69 to 71 years), completed a 2-choice RT task and amyloid beta (Aβ) positron emission tomography and MR imaging. We tested for associations between task outcomes (RT; error rate; intra-individual variability in RT) and life-course predictors including childhood cognitive ability and education.

Olfactory testing does not predict β-amyloid, MRI measures of neurodegeneration or vascular pathology in the British 1946 birth cohort.

Objective: To explore the value of olfactory identification deficits as a predictor of cerebral β-amyloid status and other markers of brain health in cognitively normal adults aged ~ 70 years.

Methods: Cross-sectional observational cohort study. 389 largely healthy and cognitively normal older adults were recruited from the MRC National Survey of Health and Development (1946 British Birth cohort) and investigated for olfactory identification deficits, as measured by the University of Pennsylvania Smell Identification Test.

Amyloid β influences the relationship between cortical thickness and vascular load.

Introduction: Cortical thickness has been proposed as a biomarker of Alzheimer's disease (AD)- related neurodegeneration, but the nature of its relationship with amyloid beta (Aβ) deposition and white matter hyperintensity volume (WMHV) in cognitively normal adults is unclear.

Methods: We investigated the influences of Aβ status (negative/positive) and WMHV on cortical thickness in 408 cognitively normal adults aged 69.2 to 71.