Abdominal myosteatosis measured with computed tomography predicts poor outcomes in patients with glioblastoma.

Background: Alterations in cellular metabolism affect cancer survival and can manifest in metrics of body composition. We investigated the effects of various body composition metrics on survival in patients with glioblastoma (GBM).

Methods: We retrospectively analyzed patients who had an abdominal and pelvic computed tomography (CT) scan performed within 1 month of diagnosis of GBM (178 participants, 102 males, 76 females, median age: 62.

The Knight Alzheimer Research Imaging dataset: a comprehensive multimodal resource for exploring aging, preclinical, and symptomatic Alzheimer disease pathology.

Background: The Knight Alzheimer Research Imaging (KARI) dataset, a compilation of data from projects conducted at Washington University in St. Louis, represents a comprehensive effort to advance our understanding of Alzheimer disease (AD) through multimodal data collection. The overarching goal is to characterize normal aging and disease progression to contribute insights into the biological changes preceding AD symptom onset.

CSF proteomics related to the neurovascular unit are associated with white matter hyperintensity volumes and cerebral microhemorrhages in autosomal dominant Alzheimer disease.

Background: Autosomal dominant Alzheimer disease (ADAD) is characterized by genetic mutations affecting the beta‐amyloid (Aβ) pathway. However, vascular and immune factors play important roles which are not completely understood. Understanding the function of the neurovascular unit (NVU) comprised of neurons, glial cells, and vasculature, at different disease stages appears ideal to developing and evaluating therapeutics.

Relationship Between 18F‐AV‐1451 Binding in Human Brain and Tissue Alterations Defined by Quantitative Gradient Recalled Echo (qGRE) MRI Measurements.

Background: The 18F‐AV‐1451 radioligand enables in‐vivo identification of tau neurofibrillary tangles that are considered as biomarkers of neurodegeneration in Alzheimer Disease (AD). However, off‐target radioligand binding is also observed in basal ganglia, known as an iron‐rich region. Hence, it is important to distinguish between radioligand‐identified tissue neurodegeneration and iron‐related radioligand binding effects.

Unraveling Alzheimer's Disease Heterogeneity: A Comparative Analysis Using HYDRA and CHIMERA.

Background: Alzheimer's Disease can present with heterogenous neurodegenerative patterns. In order to optimize clinical trials and personalized medicine, the identification and characterization of diverse pathological brain patterns associated with AD have become paramount. Optimal approaches to identify such heterogeneity are unknown.

Consistent classification of amyloid status by fasted and non‐fasted plasma Aβ42/40 and Amyloid Probability Score.

Background: It is unknown whether fasting status affects classification of amyloid status by plasma Aβ42/40.

Methods: The cohort included 50 amyloid PET positive and 50 amyloid PET negative individuals enrolled in studies of memory and aging at the Knight Alzheimer Disease Research Center (ADRC). Included individuals had a non‐fasted plasma sample and an amyloid PET scan performed within 3 months of a fasted plasma sample.

DeepSUVR: Using temporal constraints to improve SUVR and Centiloid quantification.

Background: PET quantification using the Standardised Uptake Value Ratio (SUVR) relies on the availability of a robust reference region. Intrinsic noise, spill in, and specific binding in the reference region can impact the reliability of the resulting SUVR. We evaluate a novel deep learning method trained on longitudinal data that penalises unexpected temporal changes and learns a SUVR correction factor that compensates for any noise or bias in the reference region, resulting in an improved quantification.

The prevalence of tau‐PET positivity in aging and dementia.

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

Evaluating brain age using functional connectivity in autosomal dominant Alzheimer disease.

Background: Brain‐predicted age estimates are used to quantify an individual's brain age compared to a normative trajectory. We have recently shown that brain age from structural MRI is elevated in autosomal dominant Alzheimer disease (ADAD), a unique sample that allows the study of AD progression independently of age‐related confounds. Resting‐state functional connectivity (FC) may capture a biphasic response to sporadic AD, and thus may complement structural measures of brain aging in ADAD.

Brain Volumetric Trajectories in Down Syndrome and Autosomal Dominant Alzheimer Disease.

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.

A highly accurate blood test for Alzheimer’s disease pathology has performance equivalent or superior to clinically used CSF tests.

Background: With the emergence of Alzheimer's disease (AD) disease‐modifying therapies, identifying patients who could benefit from these treatments becomes critical. We evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid‐β (Aβ) plaques and tau tangles.

Method: Plasma %p‐tau217 (ratio of phosporylated‐tau217 to non‐phosphorylated mid‐region tau) was analyzed by mass spectrometry in the Swedish BioFINDER‐2 cohort (n=1,422) and the US Knight ADRC cohort (n=337, Table 1).

Use of plasma p‐tau217 as a pre‐screening method for detecting amyloid‐PET positivity in cognitively unimpaired participants: A multicenter study.

Background: Recent results from clinical trials in Alzheimer’s disease (AD) emphasize the importance of treating early‐stage disease. However, recruitment of preclinical AD participants is difficult due to the lack of symptoms, and the costs and/or invasiveness of established CSF and PET tests. We aimed to investigate whether plasma p‐tau217 could be used to pre‐screen cognitively unimpaired (CU) potential participants for amyloid‐β (Aβ) pathology to improve the efficiency of clinical trial recruitment.

Early Alterations of White Matter Neuroinflammation in Autosomal Dominant Alzheimer's Disease.

Background: Autosomal Dominant Alzheimer's Disease (ADAD) is a rare and early‐onset form of Alzheimer's disease with a familial pattern of inheritance. While the pathological features of ADAD, such as amyloid plaques and neurofibrillary tangles, have been extensively studied, the involvement of white matter (WM) neuroinflammation is not well‐explored. In sporadic AD, the hindered ratio (HR) derived from diffusion basis spectrum imaging (DBSI) has been used to study neuroinflammation in WM.

The Association between Hepatic fat and Neuroinflammation in Midlife Obesity.

Background: Obesity in midlife, body mass index (BMI) of 30 kg/m or higher, is recognized as a contributor to Alzheimer disease (AD) later in life. Adiposity in visceral tissues such as liver is associated with increased systemic inflammation and impaired cognition. In this study, we aimed to investigate the relationship between MRI‐derived Positron Density Fat Fraction (PDFF) and brain histology and neuroinflammation using Diffusion Basis Spectrum Imaging (DBSI) in cognitively normal midlife individuals.

A multiple cohort study exploring the influence of partial volume correction on age and sex effects on tau PET imaging.

Background: Tau PET imaging has become pivotal in understanding the pathophysiological processes underlying Alzheimer disease (AD). In individuals without amyloid pathology, there is evidence tau levels are elevated with increase age and that females show greater levels of binding. An unknown question is how consistent these effects are, and whether they are susceptible to methodological choices impacting PET quantification.

The Association between the Body Fat Localization, Insulin Resistance, and Amyloid Burden in Midlife.

Background: Obesity in midlife is a risk factor for developing Alzheimer disease later in life. However, the metabolic and inflammatory effects of body fat varies based on its anatomical localization. In this study, we aimed to investigate the association of MRI‐derived abdominal visceral and subcutaneous adipose tissue (VAT and SAT), liver proton‐density fat fraction (PDFF), thigh fat‐to‐muscle ratio (FMR), and insulin resistance with whole‐brain amyloid burden in cognitively normal midlife individuals.

Alzheimer’s disease blood tests of amyloid‐beta 42/40, %p‐tau217, 181, and 205 ratios and MTBR‐243 in real‐world populations: Results from SEABIRD and BioFINDER2.

Background: Alzheimer’s disease (AD) blood tests that can identify and quantify amyloid plaques, tau tangles, and cognitive and clinical decline are needed in clinical practice, including primary care. However, these tests require validation in diverse groups and real‐world settings. The Study to Evaluate Amyloid in Blood and Imaging Related to Dementia (SEABIRD) enrolled 1,122 participants to determine the accuracy and validity of AD blood biomarkers, including amyloid‐β (Aβ) and phosphorylated tau (p‐tau) tests, in a diverse, community‐based sample of older adults compared with amyloid PET and cognitive and clinical measures to determine the impact of key factors (age, race, education, cognition, APOE genotype, and medical conditions).

Cerebral Blood Flow in Midlife Obesity: Associations with Visceral and Subcutaneous Abdominal Adipose Tissue.

Background: Obesity and higher adiposity in midlife are recognized as contributors to Alzheimer disease (AD). Neurodegeneration in AD is at least partly mediated by vascular compromise and brain hypoperfusion. In this study, we aimed to investigate the associations between BMI and abdominal visceral and subcutaneous adipose tissue (VAT, SAT) and brain cerebral blood flow (CBF) in cognitively normal midlife individuals.

Diffusion Basis Spectrum Imaging in Midlife Obesity: Associations with Abdominal Adipose Tissue.

Background: Obesity and abdominal adiposity in midlife are shown to increase the risk of Alzheimer disease. However, it is not clear whether midlife adiposity is associated with increased neuroinflammation. We aimed to investigate the associations of obesity, BMI of 30 kg/m or higher, and abdominal visceral and subcutaneous adipose tissue (VAT and SAT) with brain histology, using diffusion basis spectrum imaging (DBSI) analysis;

Method: In total, 54 cognitively normal middle‐aged subjects (50.

Lateral Ventricle Volumes Predict Hippocampal Volume and Cognition.

Background: The use of biomarkers for early detection of Alzheimer disease (AD) is crucial for developing potential treatments. As neurons die, brain structures, including the hippocampus, shrink and the cerebrospinal fluid spaces ventricles expand. However, due to its small size, hippocampal volumes can be challenging to measure.

Brain Age Gap has a Small Association with Cognition in Cognitively Normal Older Adults.

Background: Brain Age Gap (BAG) describes the difference between predicted brain age and chronological age, where a higher BAG suggests accelerated brain aging. It is estimated using machine learning techniques. The Preclinical Alzheimer Cognitive Composite (PACC) is a combination of neuropsychological tests employed in Alzheimer Disease (AD) research.

Hepatic fat is related to neurodegeneration in midlife obesity.

Background: Obesity in midlife, defined as body mass index (BMI) of 30 kg/m or higher in those between 40‐60 years, is related to higher Alzheimer’s disease (AD) later in life. Non‐alcoholic fatty liver disease, as a complication of obesity is associated with impaired cognitive function. We investigated the relationship between hepatic fat quantification by use of MRI‐derived Positron Density Fat Fraction (PDFF) and brain cortical thickness in cognitively normal midlife individuals.

Preclinical Alzheimer Disease pathology in studies of memory and aging.

Background: Preclinical Alzheimer disease (AD) describes a period prior to symptom onset during which pathology begins to accumulate. Recent development of neuroimaging‐ and biofluid‐ measures of AD pathology has allowed for in vivo quantification of preclinical pathological burden. Prior work estimated that by age 85, only one third of older adults remain free of amyloid and AD‐related atrophy.

Automated Thigh Tissue Segmentation by Vision Transformers: Application for Early Alzheimer's Diagnosis.

Background: Within the research field of neurodegenerative disorders, unbiased analysis of body fat composition, particularly muscle mass, is gaining attention as a potential biological marker for refining Alzheimer’s disease risk. The objective of this study was to employ a deep learning model for fully automated and accurate segmentation of thigh tissues, potentially contributing to early Alzheimer's diagnostics.

Method: In an IRB‐approved study, 49 participants underwent thigh Dixon MRI scans with a TR=9.

Fat to muscle ratio is related to neurodegeneration in midlife obesity.

Background: Emerging research underscores the significance of midlife obesity, defined by a BMI of 30 kg/m or higher in persons age 40‐60 years, as a risk factor for Alzheimer's disease (AD) in later life. Due to the various properties of each body component, it is important to characterize the neurodegenerative effects of fat within the muscle, known as a predictor of metabolic health and cognition. We investigated the relationships between thigh total fat‐to‐muscle ratio (FMR) and brain cortical thickness in cognitively normal midlife individuals.