Developing Topics.

Background: Education is a strong predictor influencing the dementia progression. With diminished brain integrity, cognitive reserve (CR) is thought to help preserve cognitive function and delay the symptom manifestation. Yet, scholars have not reached consensus on the extent to which education modifies brain integrity-cognitive decline associations and how it differs by sex/gender.

Using electronic medical records in hospital simulation for infection control intervention assessment.

Background: Clinical trials for assessing the effects of infection prevention and control (IPC) interventions are expensive and have shown mixed results. Mathematical models can be relatively inexpensive tools for evaluating the potential of interventions. However, capturing nuances between institutions and in patient populations have adversely affected the power of computational models of nosocomial transmission.

Alzheimer's Imaging Consortium.

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

Alzheimer's Imaging Consortium.

Background: Weakened white matter (WM) integrity is highly associated with dementia risk. Still, not everyone with WM changes develops dementia, suggesting the important role modifiable lifestyle factors may have in reducing dementia risk. We investigated how social relationships in mid-life may modify the association between WM integrity and incident dementia risk within race and sex subgroups.

Alzheimer's Imaging Consortium.

Background: Apolipoprotein e4 allele (APOE4) is the strongest genetic risk factor for late-onset Alzheimer's disease (AD) with females having higher risk than males. Compared with non-carriers, cognitively normal, middle-aged APOE4 carriers have lower cerebral blood flow (CBF) decades before clinical symptoms appear. Early intervention to protect CBF would be critical for APOE4 carriers to mitigate AD progression.

Alzheimer's Imaging Consortium.

Background: Investigations into the amyloid, tau, and neurodegeneration (ATN) framework, which is used to stage Alzheimer disease (AD) and advance clinical trials, typically consist of clinic-based non-Hispanic White (NHW) populations. The present study sought to cross-sectionally characterize AT(N) and vascular (V) imaging markers (i.e.

Alzheimer's Imaging Consortium.

Background: Virtually all adults with Down Syndrome(DS) show Alzheimer's disease(AD)-related pathologic change by the age of 40 years. While sex differences in Aß-dependent tauopathy are apparent during early sporadic AD, sex differences in the DS population remain under-investigated. Moreover, menopause onset occurs earlier in the DS population(45 years), and it remains unknown whether menopause status and hormone therapy(HT) exposure influences Aß-dependent tauopathy in women with DS.

Alzheimer's Imaging Consortium.

Background: The immune system is substantially involved in the development and progression of age-related cognitive decline and Alzheimer's disease (AD).

Method: As genetic and environmental factors interactively impact these conditions, we investigated how risk factors such as APOE genotype, age, and sex influence immune activation markers and AD biomarkers in cerebrospinal fluid (CSF) in elderly individuals enrolled in the Mayo Clinic Study of Aging cohort. Among cognitively unimpaired individuals aged over 65 at the baseline visit (N=298), we measured 365 CSF immune activation markers using the proximity extension assay.

Alzheimer's Imaging Consortium.

Background: Robust methods are needed for preclinical evaluation of novel Alzheimer Disease (AD) therapies to accelerate drug discovery. Quantitative Gradient Recalled Echo (qGRE) MRI shows significant promise to provide insight into neurodegeneration in AD prior to atrophy development in humans, with qGRE R2t* metric (tissue-specific subcomponent of R2*) highlighting areas of low neuronal density (doi:10.3233/JAD-210503).

Alzheimer's Imaging Consortium.

Background: The location of proposed brain MRI markers of small vessel disease (SVD) might reflect their pathogenesis and may translate into differential associations with cognition. We derived regional MRI markers of SVD and studied: (i) associations with cognitive performance, (ii) patterns most likely to reflect underlying SVD, (iii) mediating effects on the relationships of age and cardiovascular disease (CVD) risk with cognition.

Method: In 891 participants from The Multi-Ethnic Study of Atherosclerosis, we segmented enlarged perivascular spaces (ePVS), white matter hyperintensities (WMH) and microbleeds (MBs) using deep learning-based algorithms, and calculated white matter (WM) microstructural integrity measures of fractional anisotropy (FA), trace (TR) and free water (FW) using automated DTI-processing pipelines.

Alzheimer's Imaging Consortium.

Background: Greater adherence to the Mediterranean Diet (MeDi) is associated with lower risk for cardiovascular disease, slower cognitive decline, and reduced risk for Alzheimer's Disease (AD). However, its association with AD biomarkers is not well known. We hypothesized that greater MeDi adherence is associated with reduced amyloid and tau PET burden in a community-based sample of older adults in Northern Manhattan.

Alzheimer's Imaging Consortium.

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.

Alzheimer's Imaging Consortium.

Background: There is a strong link between tau and progression of Alzheimer's disease (AD), necessitating an understanding of tau spreading mechanisms. Prior research, predominantly in typical AD, suggested that tau propagates from epicenters (regions with earliest tau) to functionally connected regions. However, given the constrained spatial heterogeneity of tau in typical AD, validating this connectivity-based tau spreading model in AD variants with distinct tau deposition patterns is crucial.

Alzheimer's Imaging Consortium.

Background: Recent research emphasizes the significance of white matter tracts and the free-water (FW) component in understanding cognitive decline. The goal of this study is to conduct a large-scale assessment on the role of white matter microstructure on longitudinal cognitive decline.

Method: This study used a cohort collated from seven longitudinal cohorts of aging (ADNI, BIOCARD, BLSA, NACC, ROS/MAP/MARS, VMAP, and WRAP).

Alzheimer's Imaging Consortium.

Background: The variability in the regional distribution of Aß-PET signal and its relation to clinical features is debated. We used data-driven approaches to uncover heterogeneity in cortical Aß-PET signal from a large representative sample collected through the IDEAS study.

Methods: We analysed cross-sectional Aß-PET collected from 10,361 patients with MCI or mild dementia scanned in 295 PET facilities using one of the 3 FDA-approved tracers.

Alzheimer's Imaging Consortium.

Background: White matter hyperintensities (WMHs) are areas of increased signal on T2-weighted MRI scans. They vary in size, location, and intensity, suggesting different underlying conditions like small vessel disease and inflammation. This variation potentially links WMH to outcomes ranging from normal aging to severe neurological disorders.

Alzheimer's Imaging Consortium.

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.

Alzheimer's Imaging Consortium.

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.

Alzheimer's Imaging Consortium.

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.

Alzheimer's Imaging Consortium.

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/m2 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.

Alzheimer's Imaging Consortium.

Background: Differences between on- and off-target retention characteristics between [18F]MK6240 and [18F]Flortaucipir (FTP) complicate the harmonization across tracers. Our objective here was to separate the impact of the reference region by evaluating correlations between [18F]MK6240 (MK) and [18F]FTP standard uptake values (SUVs).

Method: Participants (Figure 1, n=90) received an amyloid-β (Aβ) PET scan ([11C]PIB or [18F]NAV4694) and two tau-PET scans: [18F]MK (90-110 minutes post-injection) and [18F]FTP (80-100 minutes post-injection).

Alzheimer's Imaging Consortium.

Background: Little is known about how plasma Alzheimer's disease (AD) biomarkers relate to neuroimaging biomarkers of cerebral small vessel disease (cSVD) in the context of neurodegeneration and AD pathology in late life.

Method: This cross-sectional study included 251 Multi-Ethnic Study of Atherosclerosis (MESA) Exam 6 participants with plasma AD biomarkers (Aß42/Aß40, GFAP, NfL, p-tau181, p-tau217, p-tau231; Quanterix SIMOA), MRI (neurodegeneration and cSVD), PiB (amyloid) PET, and UDSv3-based adjudicated cognitive status (69% cognitively normal, 27% MCI, 4% probable dementia) data at the Wake Forest site. Multivariable models examined relationships among cognitive status, plasma, and neuroimaging biomarkers (covariates: age, education, race, gender, smoking status, kidney function [eGFR], APOE-e4, BMI; significance at p<.

Alzheimer's Imaging Consortium.

Background: Tau-PET tracers allow for in vivo Braak staging of individuals in the Alzheimer's disease (AD) continuum. The impact of tracers' characteristics for Braak staging using tau-PET remains unclear. Therefore, we performed a head-to-head comparison of Braak staging using first- and second-generation tau-PET tracers.

Alzheimer's Imaging Consortium.

Background: Default mode network (DMN) resting state connectivity has been correlated with heightened amyloid and tau - hallmarks of Alzheimer's Disease (AD). Tau is postulated to impact a meta-temporal area including DMN-associated regions like amygdala, entorhinal cortex, fusiform gyrus, parahippocampus, inferior temporal, and middle temporal gyrus. We recruited individuals with varying cognitive status to undergo resting state connectivity and imaging with two tau tracers (Flortaucipir and MK6240).

Alzheimer's Imaging Consortium.

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.