Application of the revised criteria for diagnosis and staging of Alzheimer's disease: Drug development and clinical practice.

Unlabelled: The newly proposed revised criteria for diagnosis and staging of Alzheimer's disease (AD) by the Alzheimer's Association (AA) Workgroup represent a significant milestone in the field. These criteria offer objective measures for diagnosing and staging biological AD, bridging the gap between research and clinical care. Although implementation feasibility may vary across regions and settings, improving the availability and accuracy of biomarkers, especially plasma biomarkers, is expected to enhance the applicability of these criteria in clinical practice.

Real-Time 2D Phase-Contrast MRI to Assess Cardiac- and Respiratory-Driven CSF Movement in Normal Pressure Hydrocephalus.

Background And Purpose: In idiopathic normal pressure hydrocephalus (iNPH) patients, cerebrospinal fluid (CSF) flow is typically evaluated with a cardiac-gated two-dimensional (2D) phase-contrast (PC) MRI through the cerebral aqueduct. This approach is limited by the evaluation of a single location and does not account for respiration effects on flow. In this study, we quantified the cardiac and respiratory contributions to CSF movement at multiple intracranial locations using a real-time 2D PC-MRI and evaluated the diagnostic value of CSF dynamics biomarkers in classifying iNPH patients.

Microstructural mapping of neural pathways in Alzheimer's disease using macrostructure-informed normative tractometry.

Introduction: Diffusion-weighted magnetic resonance imaging (dMRI) is sensitive to the microstructural properties of brain tissues and shows great promise in detecting the effects of degenerative diseases. However, many approaches analyze single measures averaged over regions of interest without considering the underlying fiber geometry.

Methods: We propose a novel macrostructure-informed normative tractometry (MINT) framework to investigate how white matter (WM) microstructure and macrostructure are jointly altered in mild cognitive impairment (MCI) and dementia.

Increasing hub disruption parallels dementia severity in autosomal dominant Alzheimer's disease.

Hub regions in the brain, recognized for their roles in ensuring efficient information transfer, are vulnerable to pathological alterations in neurodegenerative conditions, including Alzheimer's disease (AD). Computational simulations and animal experiments have hinted at the theory of activity-dependent degeneration as the cause of this hub vulnerability. However, two critical issues remain unresolved.

Associations of blood pressure with white matter hyperintensities later in life; influence of short-term menopausal hormone therapy.

Objective: To assess the association of systolic and diastolic blood pressure (SBP and DBP) in recently menopausal women with white matter hyperintensity (WMH) volume later in life and determine whether short-term menopausal hormone therapy (mHT) modifies these associations.

Methods: Kronos Early Estrogen Prevention Study (KEEPS) was a multicenter, randomized, double-blinded, placebo-controlled 4-year mHT trial (oral conjugated equine estrogens or transdermal 17β-estradiol). KEEPS continuation was an observational follow-up of the participants 10 years after the end of mHT.

Overview of Alzheimer's Disease Neuroimaging Initiative and future clinical trials.

The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to optimize and validate biomarkers for clinical trials while sharing all data and biofluid samples with the global scientific community. ADNI has been instrumental in standardizing and validating amyloid beta (Aβ) and tau positron emission tomography (PET) imaging. ADNI data were used for the US Food and Drug Administration (FDA) approval of the Fujirebio and Roche Elecsys cerebrospinal fluid diagnostic tests.

Associations of Mild Behavioral Impairment Domains with Brain Volumes: Cross-sectional Analysis of Atherosclerosis Risk in Community (ARIC) Study.

Background: Mild behavioral impairment (MBI) has been associated with global brain atrophy, but the regional neural correlates of MBI symptoms are less clear, particularly among community-dwelling older individuals without dementia.

Objective: Our objective was to examine the associations of MBI domains with gray matter (GM) volumes in a large population-based sample of older adults without dementia.

Methods: We performed a cross-sectional study of 1445 community-dwelling older adults in the Atherosclerosis Risk in Communities Study who underwent detailed neurocognitive assessment and brain magnetic resonance imaging in 2011-2013.

Association of left atrial function with vascular brain injury: The Atherosclerosis Risk in Communities study.

Background And Purpose: Lower left atrial (LA) function is associated with higher dementia risk and may be mechanistically linked through vascular brain injury, an established correlate for higher dementia risk. Using data from the Atherosclerosis Risk in Communities study, we assessed the cross-sectional association between LA function and brain magnetic resonance imaging (MRI) markers of vascular brain injury.

Methods: We included 1488 participants who were free of prevalent dementia, stroke, or atrial fibrillation and who underwent a two-dimensional echocardiogram and brain MRI in 2011-2013 (mean [± standard deviation] age 76 [± 5] years, 60% female, 27% Black).

Positron emission tomography harmonization in the Alzheimer's Disease Neuroimaging Initiative: A scalable and rigorous approach to multisite amyloid and tau quantification.

Introduction: A key goal of the Alzheimer's Disease NeuroImaging Initiative (ADNI) positron emission tomography (PET) Core is to harmonize quantification of β-amyloid (Aβ) and tau PET image data across multiple scanners and tracers.

Methods: We developed an analysis pipeline (Berkeley PET Imaging Pipeline, B-PIP) for ADNI Aβ and tau PET images and applied it to PET data from other multisite studies. Steps include image pre-processing, refacing, magnetic resonance imaging (MRI)/PET co-registration, visual quality control (QC), quantification of tracer uptake, and standardization of Aβ and tau standardized uptake value ratios (SUVrs) across tracers.

Two-Stage Recruitment Design to Reduce Magnetic Resonance Imaging Screening Cost for a Theoretical Clinical Trial of White Matter Hyperintensity Progression.

Background: White matter hyperintensities (WMH) and their progression are associated with risk of dementia and stroke, so are an important target for clinical trials. The cost of broad magnetic resonance imaging (MRI) screening to identify eligible individuals, however, limits the feasibility of designing clinical trials targeting WMH. A low-cost retinal or clinical screening measure before MRI could reduce recruitment costs versus an MRI-only screening design in a hypothetical clinical trial.

Investigating the feasibility of F-flortaucipir PET imaging in the antemortem diagnosis of primary age-related tauopathy (PART): An observational imaging-pathological study.

Introduction: Primary age-related tauopathy (PART) is characterized by neurofibrillary tangles and minimal β-amyloid deposition, diagnosed postmortem. This study investigates F-flortaucipir (FTP) PET imaging for antemortem PART diagnosis.

Methods: We analyzed FTP PET scans from 50 autopsy-confirmed PART and 13 control subjects.

Plasma proteome-wide analysis of cerebral small vessel disease identifies novel biomarkers and disease pathways.

Cerebral small vessel disease (SVD), as defined by neuroimaging characteristics such as white matter hyperintensities (WMHs), cerebral microhemorrhages (CMHs), and lacunar infarcts, is highly prevalent and has been associated with dementia risk and other clinical sequelae. Although conditions such as hypertension are known to contribute to SVD, little is known about the diverse set of subclinical biological processes and molecular mediators that may also influence the development and progression of SVD. To better understand the mechanisms underlying SVD and to identify novel SVD biomarkers, we used a large-scale proteomic platform to relate 4,877 plasma proteins to MRI-defined SVD characteristics within 1,508 participants of the Atherosclerosis Risk in Communities (ARIC) Study cohort.

Implementation and validation of face de-identification (de-facing) in ADNI4.

Introduction: Recent technological advances have increased the risk that de-identified brain images could be re-identified from face imagery. The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a leading source of publicly available de-identified brain imaging, who quickly acted to protect participants' privacy.

Methods: An independent expert committee evaluated 11 face-deidentification ("de-facing") methods and selected four for formal testing.

Mayo Normative Studies: regression-based normative data for remote self-administration of the Stricker Learning Span, Symbols Test and Mayo Test Drive Screening Battery Composite and validation in individuals with Mild Cognitive Impairment and dementia.

Objective: Few normative data for unsupervised, remotely-administered computerized cognitive measures are available. We examined variables to include in normative models for Mayo Test Drive (a multi-device remote cognitive assessment platform) measures, developed normative data, and validated the norms.

Method: 1240 Cognitively Unimpaired (CU) adults ages 32-100-years (96% white) from the Mayo Clinic Study of Aging and Mayo Alzheimer's Disease Research Center with Clinical Dementia Rating of 0 were included.

Baseline multimodal imaging to predict longitudinal clinical decline in atypical Alzheimer's disease.

There are recognized neuroimaging regions of interest in typical Alzheimer's disease which have been used to track disease progression and aid prognostication. However, there is a need for validated baseline imaging markers to predict clinical decline in atypical Alzheimer's Disease. We aimed to address this need by producing models from baseline imaging features using penalized regression and evaluating their predictive performance on various clinical measures.

Anxiety in late-life depression is associated with poorer performance across multiple cognitive domains.

Objective: Anxiety is a common comorbid feature of late-life depression (LLD) and is associated with poorer global cognitive functioning independent of depression severity. However, little is known about whether comorbid anxiety is associated with a domain-specific pattern of cognitive dysfunction. We therefore examined group differences (LLD with and without comorbid anxiety) in cognitive functioning performance across multiple domains.

Can integration of Alzheimer's plasma biomarkers with MRI, cardiovascular, genetics, and lifestyle measures improve cognition prediction?

There is increasing interest in Alzheimer's disease related plasma biomarkers due to their accessibility and scalability. We hypothesized that integrating plasma biomarkers with other commonly used and available participant data (MRI, cardiovascular factors, lifestyle, genetics) using machine learning (ML) models can improve individual prediction of cognitive outcomes. Further, our goal was to evaluate the heterogeneity of these predictors across different age strata.

Visual assessments of 11 C-Pittsburgh compound-B PET vs. 18 F-flutemetamol PET across the age spectrum.

Objective: Visual assessments of amyloid-β PET, used for Alzheimer's disease (AD) diagnosis and treatment evaluation, require a careful approach when different PET ligands are utilized. Because the gray matter (GM) and white matter (WM) ligand bindings vary with age, the objective was to investigate the agreement between visual reads of 11 C- and 18 F-PET scans.

Methods: Cognitively unimpaired (CU) younger adults ( N  =   30; 39.