Biomarkers.

Background: Specific PSEN1 mutations cause early-onset AD but their effects on blood biomarker levels are unknown. We evaluated autopsy-confirmed individuals affected by six different PSEN1 mutations; two of known (L381V, C410Y) and three (A426P/E318G, M233L, and V261I) of unknown pathogenic status. The sixth patient had Autosomal Dominant AD (ADAD) not yet genotyped.

Biomarkers.

Background: The APOE4 genotype appears to confer differential risk of Alzheimer's disease for women compared to men. As APOE4 effects in midlife women can be subtle (e.g.

Biomarkers.

Background: Plasma biomarkers have been widely evaluated as surrogate markers for brain Alzheimer's disease (AD) pathology. However, studies in diverse populations with lower socioeconomic status (SES) are limited. We evaluated associations between different plasma biomarkers and brain amyloid beta (Aβ) and tau positron emission tomography (PET) in a longitudinal cohort of cognitively normal participants from a medically- and economically-underserved Rust Belt region of Western Pennsylvania, USA.

Biomarkers.

Background: Blood-based biomarkers offer a cost-effective and simple alternative for clinical use in the context of Alzheimer's disease (AD). It has already been shown that plasma phosphorylated tau at threonine 217 (p-tau217) is associated with amyloid (Aβ), neurofibrillary tau tangles, and cognitive decline. Longitudinal studies confirmed its ability to track AD progression.

Biomarkers.

Background: Identifying individuals' levels of tau PET pathology could prove to be beneficial in clinical settings, given that emerging therapies aimed reducing Aβ seem to be most effective in these individuals. Here, we present the cases of four patients who visited the memory clinic at the University of Pittsburgh Medical Center between June and December 2023 and underwent both Aβ and tau-PET scans.

Method: These individuals had standard clinical and cognitive outcomes, typical blood tests order in patients with memory impairment, MRI, and, as part of the HEAD study, PET PIB Aβ and two tau PET tracers (MK6240 and Flortaucipir).

Biomarkers.

Background: Tau PET provides continuous measurements of tau tangle pathology in the human brain. However, establishing cutoffs is crucial for selecting individuals for treatment in clinical trials or practice. In the absence of postmortem data, PET cutoffs must be established using statistical methods based on what is considered normal tracer uptake.

Biomarkers.

Background: Recent anti-amyloid clinical trials have incorporated plasma glial fibrillary acidic protein (GFAP) as an exploratory endpoint, reporting a notable decrease in plasma GFAP levels over time. Additionally, plasma GFAP has been associated with Aβ pathology and cognitive decline in individuals with cognitive impairment, making it a robust biomarker of neuroinflammation for Alzheimer's disease (AD). Here, we tested the utility of changes in plasma GFAP as a secondary endpoint in AD clinical trials focusing on cognitively impaired (CI) individuals.

Biomarkers.

Background: Plasma phospho-tau217 (p-tau217) is a promising blood-based biomarkers for Alzheimer's disease (AD). However, the accessibility of pTau217 tests for both research and clinical applications has been constrained. Previous studies focused on highly-phenotyped cohorts that differ substantially from the wider population.

Biomarkers.

Background: Plasma p-tau217 is probably the best-performing blood biomarker to detect brain amyloid-beta (Aβ) accumulation. However, previous studies were mostly performed in highly selected cohorts. Thus, it is unclear if it can be used independently of confirmatory neuroimaging tests to identify individuals with abnormal brain Ab load in the wider population where positron emission tomography (PET) may be unavailable.

Biomarkers.

Background: Amyloid β (Aβ) deposition in the brain is a pathological hallmark of Alzheimer's disease (AD). While immunoprecipitation-mass spectrometry (IP-MS) stands out as an accurate method for quantifying blood-based Aβ peptides, its major limitations such as prolonged sample preparation, extensive analysis time, large specimen volume, and high costs, present opportunities for improvement. Consequently, we aimed to develop a novel plasma IP-MS Aβ assay that employs simplified and significantly shorter analytical procedures, along with much-reduced sample volumes.

Public Health.

Background: Higher Mediterranean- DASH for Neurodegenerative Delay (MIND) diet scores have previously been associated with larger total brain volume (TBV) in the Framingham Offspring Study (FOS) community-based cohort. We investigated cross-sectional relationships between the MIND diet and structural brain imaging volumes and white matter hyperintensity volume (WMHV) across six community-based cohorts.

Method: We analyzed data from 3130 dementia-, stroke- and other neurological disease free adults (aged 65 to 74) who participated in the Atherosclerosis Risk in Communities (ARIC) cohort, Cardiovascular Health Study (CHS), Three City (3C) cohort, FOS cohort, Rotterdam Study (RS) or the Study of Health in Pomerania (SHIP) cohort.

Public Health.

Background: Neighborhood walkability may affect cognitive impairment through promotion of physical activity. However, most studies are conducted in urban, predominantly White samples. We assessed how walkability is related to presence of cognitive impairment and whether the relation differs by neighborhood population density (differences in likelihood of promoting physical activity) and/or racial composition (differences in quality of neighborhood resources).

Public Health.

Background: Ethnic and racial diversity in clinical research is critical for developing generalizable treatments and caregiving strategies. Barriers to participation among persons from underrepresented groups (URG) are systemic in clinical research. To increase URG research participation, we designed a community-based data collection site where study participants complete full research visits.

Public Health.

Background: Low levels of high density lipoprotein cholesterol (HDL-c) are a risk factors for atherosclerotic cardiovascular disease (ASCVD). ASCVD can increase the risk for dementia. However, the link between HDL-C and incidence of dementia remain less clear specifically in women.

Biomarkers.

Background: Differences in Alzheimer's disease (AD) amyloid, tau, vascular, and neurodegeneration (ATV(N)) biomarkers by sex and racialized group have been reported, but little is known about the intersections of sex and racialization on these biomarkers.

Methods: Participants in this cross-sectional analysis are from the Connectomics of Brain Aging study, a Human Connectome Project protocol evaluating brain structure and function in aging and AD. We measured A using global amyloid SUVR from C-PiB PET, T using plasma p-tau 217, V using lobar unhealthy white matter connectivity (UWMC), a novel measure indicating the proportion of WM connections impacted by white matter hyperintensities (WMH), and N using cortical thickness from an AD-based meta-region of interest.

Biomarkers.

Background: Adults with Down Syndrome (DS) clearly show a higher risk of developing Alzheimer's disease (AD) when compared with the general population. Thus, it is important to investigate the role AD-related biomarkers in adults with DS. Here we have performed genome-wide association analyses on Tau-PET and plasma Tau levels in the participants of the Alzheimer's Biomarker Consortium - Down Syndrome (ABC-DS).

Biomarkers.

Background: Adults with Down Syndrome (DS) are at higher risk for Alzheimer's disease (AD) compared to the general population due to trisomy of chromosome 21. Thus, it is important to investigate the role AD-related biomarkers in adults with DS. Here we have performed genome-wide association analyses on amyloid-PET and plasma amyloid levels in the participants of the Alzheimer's Biomarker Consortium - Down Syndrome (ABC-DS).

Biomarkers.

Background: Identification of cognitively unimpaired (CU) individuals who may progress to mild cognitive impairment (MCI), is a pressing issue in the Alzheimer's disease (AD) field, since therapeutic interventions may be more effective in the absence of cognitive impairment and neurodegeneration. CU individuals positive for amyloid and tau PET are very likely in the AD pathway. In out-patient cognitive screening, we use rapid and simple tests such as The Montreal Cognitive Assessment (MoCA) - a composite of executive, visuospatial, naming, attention, language, abstraction, delayed recall, and orientation performances.

Biomarkers.

Background: Plasma p-tau217 is a highly promising biomarker for detecting Alzheimer's disease (AD) pathology. However, it is unclear how p-tau217 assays from different sources perform compared to one another. Moreover, studies in diverse cohorts and population-based settings are limited.

Developing Topics.

Background: The residual approach has found wide application in researching cognitive resilience, a phenomenon conceptually understood as cognitive performance being better-than-typical for an individual, despite apparent AD pathology. The standard residual approach extracts information about an individual's resilience from the residuals of a linear model predicting cognition. This approach is subject to several limiting assumptions.

Alzheimer's Imaging Consortium.

Background: Tau PET provides continuous measurements of tau tangle pathology in the human brain. However, establishing cutoffs is crucial for selecting individuals for treatment in clinical trials or practice. In the absence of postmortem data, PET cutoffs must be established using statistical methods based on what is considered normal tracer uptake.

Alzheimer's Imaging Consortium.

Background: Identification of cognitively unimpaired (CU) individuals who may progress to mild cognitive impairment (MCI), is a pressing issue in the Alzheimer's disease (AD) field, since therapeutic interventions may be more effective in the absence of cognitive impairment and neurodegeneration. CU individuals positive for amyloid and tau PET are very likely in the AD pathway. In out-patient cognitive screening, we use rapid and simple tests such as The Montreal Cognitive Assessment (MoCA) - a composite of executive, visuospatial, naming, attention, language, abstraction, delayed recall, and orientation performances.

Dementia Care Research and Psychosocial Factors.

Background: People living with dementia (PwD) experience progressive functional decline with increasing dependence on their caregivers. Advanced care planning (ACP) has the potential to promote quality of life, reduce iatrogenic harm, and minimize overutilization of healthcare resources, yet planning ahead in the context of dementia is challenging and requires consideration of numerous factors over an extended period of time. We examined caregivers' perceptions of current and end-stage medical care preferences in PwD and the impact of ACP-related discussions between caregivers and PwD.

Dementia Care Research and Psychosocial Factors.

Background: Research on the relationship between self-efficacy and symptoms of depression and anxiety among individuals with mild cognitive impairment (MCI) has been limited. Furthermore, few studies have explored this relationship within the context of dyadic couples (patient/care partners) rather than focusing solely on individuals. The purpose of this study was to examine the associations between self-efficacy in patient/care partner couples dealing with mild cognitive impairment and their symptoms of depression and anxiety using a dyadic analysis approach.

Dementia Care Research and Psychosocial Factors.

Background: As the landscape of ADRD diagnoses evolves to include biomarker testing, there is a pressing need to understand the unique experiences, challenges, and support needs of families undergoing evaluations of cognitive decline, particularly in a manner that prioritizes cultural considerations from voices historically underrepresented in ADRD research. The current study aims to understand the AD biomarker disclosure journey of persons from underrepresented groups with the goal of informing culturally responsive approaches to the care of patients and their families navigating the complexities of ADRD diagnoses.

Method: Virtual focus groups are being conducted over a secure video conferencing platform, with a trained facilitator guiding the discussion.