The interplay of age, gender and amyloid on brain and cognition in mid-life and older adults.

Deficits in memory are seen as a canonical sign of aging and a prodrome to dementia in older adults. However, our understanding of age-related cognition and brain morphology occurring throughout a broader spectrum of adulthood remains limited. We quantified the relationship between cognitive function and brain morphology (sulcal width, SW) using three cross-sectional observational datasets (PISA, AIBL, ADNI) from mid-life to older adulthood, assessing the influence of age, sex, amyloid (Aβ) and genetic risk for dementia.

Autoantibodies to BACE1 promote Aβ accumulation and neurodegeneration in Alzheimer's disease.

The profile of autoantibodies is dysregulated in patients with Alzheimer's disease (AD). Autoantibodies to beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) are present in human blood. This study aims to investigate the clinical relevance and pathophysiological roles of autoantibodies to BACE1 in AD.

3T sodium-MRI as predictor of neurocognition in nondemented older adults: a cross sectional study.

Dementia is a burgeoning global problem. Novel magnetic resonance imaging (MRI) metrics beyond volumetry may bring new insight and aid clinical trial evaluation of interventions early in the Alzheimer's disease course to complement existing imaging and clinical metrics. To determine whether: (i) normalized regional sodium-MRI values (Na-SI) are better predictors of neurocognitive status than volumetry (ii) cerebral amyloid PET status improves modelling.

Clearance and transport of amyloid β by peripheral monocytes correlate with Alzheimer's disease progression.

Impaired clearance of amyloid β (Aβ) in late-onset Alzheimer's disease (AD) affects disease progression. The role of peripheral monocytes in Aβ clearance from the central nervous system (CNS) is unclear. We use a flow cytometry assay to identify Aβ-binding monocytes in blood, validated by confocal microscopy, Western blotting, and mass spectrometry.

Harmonizing tau positron emission tomography in Alzheimer's disease: The CenTauR scale and the joint propagation model.

Introduction: Tau-positron emission tomography (PET) outcome data of patients with Alzheimer's disease (AD) cannot currently be meaningfully compared or combined when different tracers are used due to differences in tracer properties, instrumentation, and methods of analysis.

Methods: Using head-to-head data from five cohorts with tau PET radiotracers designed to target tau deposition in AD, we tested a joint propagation model (JPM) to harmonize quantification (units termed "CenTauR" [CTR]). JPM is a statistical model that simultaneously models the relationships between head-to-head and anchor point data.

Clinical Evidence for GLP-1 Receptor Agonists in Alzheimer's Disease: A Systematic Review.

Background: Alzheimer's disease (AD) is the most common cause of dementia. While preclinical studies have shown benefits of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in targeting core AD pathology, clinical studies are limited.

Objective: A systematic review was performed to evaluate GLP-1 RAs in AD for their potential to target core AD pathology and improve cognition.

Impact of PET Reconstruction on Amyloid-β Quantitation in Cross-Sectional and Longitudinal Analyses.

Amyloid-β (Aβ) accumulation in Alzheimer disease (AD) is typically measured using SUV ratio and the centiloid (CL) scale. The low spatial resolution of PET images is known to degrade quantitative metrics because of the partial-volume effect. This article examines the impact of spatial resolution, as determined by the reconstruction configuration, on the Aβ PET quantitation in both cross-sectional and longitudinal data.

Inter-scanner Aβ-PET harmonization using barrel phantom spatial resolution matching.

Introduction: The standardized uptake value ratio (SUVR) is used to measure amyloid beta-positron emission tomography (Aβ-PET) uptake in the brainDifferences in PET scanner technologies and image reconstruction techniques can lead to variability in PET images across scanners. This poses a challenge for Aβ-PET studies conducted in multiple centers. The aim of harmonization is to achieve consistent Aβ-PET measurements across different scanners.

Brain 11β-Hydroxysteroid Dehydrogenase Type 1 Occupancy by Xanamem™ Assessed by PET in Alzheimer's Disease and Cognitively Normal Individuals.

Background: 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regulates intracellular cortisol and its inhibition by the small molecule inhibitor, Xanamem™, may provide a disease-modifying strategy for Alzheimer's disease (AD). Animal models suggest a range of 30-60% enzyme inhibition may suffice to provide neuroprotection.

Objective: To determine the regional brain occupancy of 11β-HSD1 by Xanamem™ in cognitively normal participants (CN) and mild cognitive impairment (MCI)/mild AD patients to investigate potential dosing ranges for future efficacy studies.

Altered grey matter structural covariance in chronic moderate-severe traumatic brain injury.

Traumatic brain injury (TBI) alters brain network connectivity. Structural covariance networks (SCNs) reflect morphological covariation between brain regions. SCNs may elucidate how altered brain network topology in TBI influences long-term outcomes.

Physical activity and brain amyloid beta: A longitudinal analysis of cognitively unimpaired older adults.

Introduction: The current study evaluated the relationship between habitual physical activity (PA) levels and brain amyloid beta (Aβ) over 15 years in a cohort of cognitively unimpaired older adults.

Methods: PA and Aβ measures were collected over multiple timepoints from 731 cognitively unimpaired older adults participating in the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Aging. Regression modeling examined cross-sectional and longitudinal relationships between PA and brain Aβ.

Tackling Dementia Together via The Australian Dementia Network (ADNeT): A Summary of Initiatives, Progress and Plans.

In 2018, the Australian Dementia Network (ADNeT) was established to bring together Australia's leading dementia researchers, people with living experience and clinicians to transform research and clinical care in the field. To address dementia diagnosis, treatment, and care, ADNeT has established three core initiatives: the Clinical Quality Registry (CQR), Memory Clinics, and Screening for Trials. Collectively, the initiatives have developed an integrated clinical and research community, driving practice excellence in this field, leading to novel innovations in diagnostics, clinical care, professional development, quality and harmonization of healthcare, clinical trials, and translation of research into practice.

Longitudinal trajectories of basal forebrain volume in normal aging and Alzheimer's disease.

Dysfunction of the cholinergic basal forebrain (BF) system and amyloid-β (Aβ) deposition are early pathological features in Alzheimer's disease (AD). However, their association in early AD is not well-established. This study investigated the nature and magnitude of volume loss in the BF, over an extended period, in 516 older adults who completed Aβ-PET and serial magnetic resonance imaging scans.

Associations Between Amyloid Burden, Hypoxemia, Sleep Architecture, and Cognition in Obstructive Sleep Apnea.

Background: Obstructive sleep apnea (OSA) is associated with an increased risk of amyloid-β (Aβ) burden, the hallmark of Alzheimer's disease, and cognitive decline.

Objective: To determine the differential impacts of hypoxemia and slow-wave sleep disruption on brain amyloid burden, and to explore the effects of hypoxemia, slow-wave sleep disruption, and amyloid burden on cognition in individuals with and without OSA.

Methods: Thirty-four individuals with confirmed OSA (mean±SD age 57.

Biostatistical Estimation of Tau Threshold Hallmarks (BETTH) Algorithm for Human Tau PET Imaging Studies.

A methodology for determining tau PET thresholds is needed to confidently detect early tau deposition. We compared multiple threshold-determining methods in participants who underwent either F-flortaucipir or F-MK-6240 PET scans. F-flortaucipir ( = 798) and F-MK-6240 ( = 216) scans were processed and sampled to obtain regional SUV ratios.

A universal neocortical mask for Centiloid quantification.

Introduction: The Centiloid (CL) project was developed to harmonize the quantification of amyloid beta (Aβ) positron emission tomography (PET) scans to a unified scale. The CL neocortical mask was defined using C Pittsburgh compound B (PiB), overlooking potential differences in regional distribution among Aβ tracers. We created a universal mask using an independent dataset of five Aβ tracers, and investigated its impact on inter-tracer agreement, tracer variability, and group separation.

CenTauR: Toward a universal scale and masks for standardizing tau imaging studies.

Introduction: Recently, an increasing number of tau tracers have become available. There is a need to standardize quantitative tau measures across tracers, supporting a universal scale. We developed several cortical tau masks and applied them to generate a tau imaging universal scale.

Tau in dementia with Lewy bodies.

Objective: Neurofibrillary tangles are present in a proportion of people with dementia with Lewy bodies and may be associated with worse cognition. Recent advances in biomarkers for Alzheimer's disease include second-generation tau positron emission tomography as well as the detection of phosphorylated tau at threonine 181 (p-tau181) in plasma. This study aimed to investigate tau in people with dementia with Lewy bodies using a second-generation tau positron emission tomography tracer as well as plasma p-tau181.

Associations of Enlarged Perivascular Spaces With Brain Lesions, Brain Age, and Clinical Outcomes in Chronic Traumatic Brain Injury.

Background And Objectives: Enlarged perivascular spaces (ePVS) have been identified as a key signature of glymphatic system dysfunction in neurologic conditions. The incidence and clinical implications of ePVS after traumatic brain injury (TBI) are not yet understood. We investigated whether individuals with chronic moderate-to-severe TBI had an increased burden of ePVS and whether ePVS burden is modulated by the presence of focal lesions, older brain age, and poorer sleep quality.

Novel Alzheimer's disease locus identified by genome-wide association analysis of cerebral tau deposition on PET.

Determining the genetic architecture of Alzheimer's disease (AD) pathologies can enhance mechanistic understanding and inform precision medicine strategies. Here, we performed a genome-wide association study of cortical tau quantified by positron emission tomography in 3,136 participants from 12 independent studies. The locus was associated with tau deposition.

Development, initial validation, and application of a visual read method for [F]MK-6240 tau PET.

Background: The positron emission tomography (PET) radiotracer [F]MK-6240 exhibits high specificity for neurofibrillary tangles (NFTs) of tau protein in Alzheimer's disease (AD), high sensitivity to medial temporal and neocortical NFTs, and low within-brain background. Objectives were to develop and validate a reproducible, clinically relevant visual read method supporting [F]MK-6240 use to identify and stage AD subjects versus non-AD and controls.

Methods: Five expert readers used their own methods to assess 30 scans of mixed diagnosis (47% cognitively normal, 23% mild cognitive impairment, 20% AD, 10% traumatic brain injury) and provided input regarding regional and global positivity, features influencing assessment, confidence, practicality, and clinical relevance.

Tau, β-Amyloid, and Glucose Metabolism Following Service-Related Traumatic Brain Injury in Vietnam War Veterans: The Australian Imaging Biomarkers and Lifestyle Study of Aging-Veterans Study (AIBL-VETS).

Traumatic brain injury (TBI) is common among military veterans and has been associated with an increased risk of dementia. It is unclear if this is due to increased risk for Alzheimer's disease (AD) or other mechanisms. This case control study sought evidence for AD, as defined by the 2018 National Institute on Aging - Alzheimer's Association (NIA-AA) research framework, by measuring tau, β-amyloid, and glucose metabolism using positron emission tomography (PET) in veterans with service-related TBI.

Plasma Glial Fibrillary Acidic Protein Is Associated with 18F-SMBT-1 PET: Two Putative Astrocyte Reactivity Biomarkers for Alzheimer's Disease.

Background: Astrocyte reactivity is an early event along the Alzheimer's disease (AD) continuum. Plasma glial fibrillary acidic protein (GFAP), posited to reflect astrocyte reactivity, is elevated across the AD continuum from preclinical to dementia stages. Monoamine oxidase-B (MAO-B) is also elevated in reactive astrocytes observed using 18F-SMBT-1 PET in AD.