Pick a PACC: Comparing domain-specific and general cognitive composites in Alzheimer disease research.

Objective: We aimed to illustrate how complex cognitive data can be used to create domain-specific and general cognitive composites relevant to Alzheimer disease research.

Method: Using equipercentile equating, we combined data from the Charles F. and Joanne Knight Alzheimer Disease Research Center that spanned multiple iterations of the Uniform Data Set.

Presenilin-1 mutation position influences amyloidosis, small vessel disease, and dementia with disease stage.

Introduction: Amyloidosis, including cerebral amyloid angiopathy, and markers of small vessel disease (SVD) vary across dominantly inherited Alzheimer's disease (DIAD) presenilin-1 (PSEN1) mutation carriers. We investigated how mutation position relative to codon 200 (pre-/postcodon 200) influences these pathologic features and dementia at different stages.

Methods: Individuals from families with known PSEN1 mutations (n = 393) underwent neuroimaging and clinical assessments.

Investigating White Matter Neuroinflammation in Alzheimer Disease Using Diffusion-Based Neuroinflammation Imaging.

Background And Objectives: Alzheimer disease (AD) is primarily associated with accumulations of amyloid plaques and tau tangles in gray matter, however, it is now acknowledged that neuroinflammation, particularly in white matter (WM), significantly contributes to the development and progression of AD. This study aims to investigate WM neuroinflammation in the continuum of AD and its association with AD pathologies and cognition using diffusion-based neuroinflammation imaging (NII).

Methods: This is a cross-sectional, single-center, retrospective evaluation conducted on an observational study of 310 older research participants who were enrolled in the Knight Alzheimer's Disease Research Center cohort.

Predicting cognitive decline: Which is more useful, baseline amyloid levels or longitudinal change?

The use of biomarkers for the early detection of Alzheimer's disease (AD) is crucial for developing potential therapeutic treatments. Positron Emission Tomography (PET) is a well-established tool used to detect β-amyloid (Aβ) plaques in the brain. Previous studies have shown that cross-sectional biomarkers can predict cognitive decline (Schindler et al.

Investigation of sex differences in mutation carriers of the Dominantly Inherited Alzheimer Network.

Introduction: Studies suggest distinct differences in the development, presentation, progression, and response to treatment of Alzheimer's disease (AD) between females and males. We investigated sex differences in cognition, neuroimaging, and fluid biomarkers in dominantly inherited AD (DIAD).

Methods: Three hundred twenty-five mutation carriers (55% female) and one hundred eighty-six non-carriers (58% female) of the Dominantly Inherited Alzheimer Network Observational Study were analyzed.

Oral antimicrobial therapy for cellulitis versus outpatient parenteral antimicrobial therapy: a single-centre audit of cellulitis outcomes.

Background: Cellulitis is a common acute skin and soft tissue infection that causes substantial morbidity and healthcare costs.

Aims: To audit the impact on cellulitis management, regimen tolerability and outcomes of switching from outpatient parenteral antimicrobial therapy (OPAT) using intravenous (i.v.

The Dominantly Inherited Alzheimer Network: A neuroimaging resource.

The Dominantly Inherited Alzheimer Network (DIAN) unites researchers aiming to understand autosomal dominant Alzheimer’s disease (ADAD). By longitudinally monitoring families worldwide, the DIAN Observational Study maintains an unprecedented resource of deeply phenotyped, freely available neuroimaging data on individuals with ADAD and their healthy relatives.

Longitudinal head-to-head comparison of C-PiB and F-florbetapir PET in a Phase 2/3 clinical trial of anti-amyloid-β monoclonal antibodies in dominantly inherited Alzheimer's disease.

Purpose: Pittsburgh Compound-B (C-PiB) and F-florbetapir are amyloid-β (Aβ) positron emission tomography (PET) radiotracers that have been used as endpoints in Alzheimer's disease (AD) clinical trials to evaluate the efficacy of anti-Aβ monoclonal antibodies. However, comparing drug effects between and within trials may become complicated if different Aβ radiotracers were used. To study the consequences of using different Aβ radiotracers to measure Aβ clearance, we performed a head-to-head comparison of C-PiB and F-florbetapir in a Phase 2/3 clinical trial of anti-Aβ monoclonal antibodies.

APOE ε4 genotype, amyloid-β, and sex interact to predict tau in regions of high APOE mRNA expression.

The apolipoprotein E () ε4 allele is strongly linked with cerebral β-amyloidosis, but its relationship with tauopathy is less established. We investigated the relationship between ε4 carrier status, regional amyloid-β (Aβ), magnetic resonance imaging (MRI) volumetrics, tau positron emission tomography (PET), messenger RNA (mRNA) expression maps, and cerebrospinal fluid phosphorylated tau (CSF ptau). Three hundred fifty participants underwent imaging, and 270 had ptau.

Amyloid-Related Imaging Abnormalities in the DIAN-TU-001 Trial of Gantenerumab and Solanezumab: Lessons from a Trial in Dominantly Inherited Alzheimer Disease.

Objective: To determine the characteristics of participants with amyloid-related imaging abnormalities (ARIA) in a trial of gantenerumab or solanezumab in dominantly inherited Alzheimer disease (DIAD).

Methods: 142 DIAD mutation carriers received either gantenerumab SC (n = 52), solanezumab IV (n = 50), or placebo (n = 40). Participants underwent assessments with the Clinical Dementia Rating® (CDR®), neuropsychological testing, CSF biomarkers, β-amyloid positron emission tomography (PET), and magnetic resonance imaging (MRI) to monitor ARIA.

Investigating Tau and Amyloid Tracer Skull Binding in Studies of Alzheimer Disease.

Off-target binding of [F]flortaucipir (FTP) can complicate quantitative PET analyses. An underdiscussed off-target region is the skull. Here, we characterize how often FTP skull binding occurs, its influence on estimates of Alzheimer disease pathology, its potential drivers, and whether skull uptake is a stable feature across time and tracers.

Baseline Microglial Activation Correlates With Brain Amyloidosis and Longitudinal Cognitive Decline in Alzheimer Disease.

Background And Objectives: This study aims to quantify microglial activation in individuals with Alzheimer disease (AD) using the 18-kDa translocator protein (TSPO) PET imaging in the hippocampus and precuneus, the 2 AD-vulnerable regions, and to evaluate the association of baseline neuroinflammation with amyloidosis, tau, and longitudinal cognitive decline.

Methods: Twenty-four participants from the Knight Alzheimer Disease Research Center (Knight ADRC) were enrolled and classified into stable cognitively normal, progressor, and symptomatic AD groups based on clinical dementia rating (CDR) at 2 or more clinical assessments. The baseline TSPO radiotracer [11C]PK11195 was used to image microglial activation.

Beta-amyloid moderates the relationship between cortical thickness and attentional control in middle- and older-aged adults.

Although often unmeasured in studies of cognition, many older adults possess Alzheimer disease (AD) pathologies such as beta-amyloid (Aβ) deposition, despite being asymptomatic. We were interested in examining whether the behavior-structure relationship observed in later life was altered by the presence of preclinical AD pathology. A total of 511 cognitively unimpaired adults completed magnetic resonance imaging and three attentional control tasks; a subset (n = 396) also underwent Aβ-positron emissions tomography.

Sex-Specific Patterns of Body Mass Index Relationship with White Matter Connectivity.

Background: Obesity is an increasingly recognized modifiable risk factor for Alzheimer's disease (AD). Increased body mass index (BMI) is related to distinct changes in white matter (WM) fiber density and connectivity.

Objective: We investigated whether sex differentially affects the relationship between BMI and WM structural connectivity.

Intracranial internal carotid artery calcification is not predictive of future cognitive decline.

Background: Intracranial internal carotid artery (ICA) calcification is a common incidental finding in non-contrast head CT. We evaluated the predictive value of ICAC (ICAC) for future risk of cognitive decline and compared the results with conventional imaging biomarkers of dementia.

Methods: In a retrospective observational cohort, we included 230 participants with a PET-CT scan within 18 months of a baseline clinical assessment and longitudinal imaging assessments.

A callosal biomarker of behavioral intervention outcomes for autism spectrum disorder? A case-control feasibility study with diffusion tensor imaging.

Tentative results from feasibility analyses are critical for planning future randomized control trials (RCTs) in the emerging field of neural biomarkers of behavioral interventions. The current feasibility study used MRI-derived diffusion imaging data to investigate whether it would be possible to identify neural biomarkers of a behavioral intervention among people diagnosed with autism spectrum disorder (ASD). The corpus callosum has been linked to cognitive processing and callosal abnormalities have been previously found in people diagnosed with ASD.

Comparing cortical signatures of atrophy between late-onset and autosomal dominant Alzheimer disease.

Defining a signature of cortical regions of interest preferentially affected by Alzheimer disease (AD) pathology may offer improved sensitivity to early AD compared to hippocampal volume or mesial temporal lobe alone. Since late-onset Alzheimer disease (LOAD) participants tend to have age-related comorbidities, the younger-onset age in autosomal dominant AD (ADAD) may provide a more idealized model of cortical thinning in AD. To test this, the goals of this study were to compare the degree of overlap between the ADAD and LOAD cortical thinning maps and to evaluate the ability of the ADAD cortical signature regions to predict early pathological changes in cognitively normal individuals.

The brain-derived neurotrophic factor Val66Met genotype does not influence the grey or white matter structures underlying recognition memory.

A single nucleotide polymorphism (SNP) in the gene coding for brain-derived neurotrophic factor (BDNF) has previously been associated with a reduction in recognition memory performance. While previous findings have highlighted that this SNP contributes to recognition memory, little is known about its influence on subprocesses of recognition, familiarity and recollection. Previous research has reported reduced hippocampal volume and decreased fractional anisotropy in carriers of the Met allele across a range of white matter tracts, including those networks that may support recognition memory.

Human Sensory LTP Predicts Memory Performance and Is Modulated by the ValMet Polymorphism.

: Long-term potentiation (LTP) is recognised as a core neuronal process underlying long-term memory. However, a direct relationship between LTP and human memory performance is yet to be demonstrated. The first aim of the current study was thus to assess the relationship between LTP and human long-term memory performance.

No evidence for systematic white matter correlates of dyslexia and dyscalculia.

Learning disabilities such as dyslexia, dyscalculia and their comorbid manifestation are prevalent, affecting as much as 15% of the population. Structural neuroimaging studies have indicated that these disorders can be related to differences in white matter integrity, although findings remain disparate. In this study, we used a unique design composed of individuals with dyslexia, dyscalculia, both disorders and controls, to systematically explore differences in fractional anisotropy across groups using diffusion tensor imaging.