Biomarkers.

Background: Plasma Aβ42/40 and p-tau217 can predict amyloid positivity in cross-sectional studies. However, it is unclear how plasma biomarkers perform longitudinally, which is important to inform their utility in tracking disease progression. The goal of this study is to describe temporal evolutions of plasma Aβ42/40 and ptau217 ratio (p-tau217r) measured via mass spectrometry, p-tau217 measured via an immunoassay, and amyloid PET.

Biomarkers.

Background: There is a consensus in the Alzheimer's disease and related dementias (ADRD) community that data sharing can accelerate science leading to better biomarkers, treatments and preventative measures. However, the ADRD community faces extensive challenges when it comes to sharing of complex biomarker data due to heavy-handed data sharing mandates and various types of restrictions.

Methods: The Global Alzheimer's Association Interactive Network (GAAIN) and the Alzheimer's Disease (AD) Data Initiative have pioneered methods in federated data sharing and learning methodologies by allowing data partners to share their data while protecting their data ownership rights.

Public Health.

Background: Estimates of the prevalence of preclinical amyloid positivity in the US general population are of great interest to the field, but difficult to measure and thus unavailable in representative studies. A statistical approach from causal inference, 'transport', may allow for improved generalizability of findings from a sample of persons from one population to another. We aimed to explore the feasibility and validity of extending results from a deeply-phenotyped convenience sample, the Alzheimer's Disease Neuroimaging Initiative (ADNI), to a representative target sample, the Atherosclerosis Risk in Communities Study PET Amyloid Imaging Study (ARIC-PET) - with "proof of concept" defined by the performance of the transport estimator in recovering the observed prevalence of amyloid positivity in ARIC-PET.

Public Health.

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.

Public Health.

Background: The Aging and Cognitive Health Evaluation in Elders (ACHIEVE, Clinicaltrials.gov Identifier: NCT03243422) randomized trial investigated the effect of hearing intervention versus health education control on 3-year cognitive change among dementia-free older adults with untreated hearing loss. Participants were recruited from the Atherosclerosis Risk in Communities (ARIC) study (n = 238) or de novo from the community (n = 739).

Biomarkers.

Background: Olfactory impairment appears early in the course of Alzheimer's Disease (AD) and may serve as a non-invasive early marker of AD. Few studies have examined the association between olfaction and blood biomarkers of AD neuropathology in large, diverse, community-based populations. Blood levels of amyloid-beta (Aβ and Aβ), phosphorylated-tau (p-tau) forms, glial fibrillary acidic protein (GFAP), and neurofilament-light chain (NfL) appear to reliably reflect corresponding brain neuropathologies and neurodegeneration.

Biomarkers.

Background: Older adults with dual cognitive and mobility impairments have higher financial costs and poorer quality of life than adults with either impairment alone. Blood biomarkers of Alzheimer Disease (AD) pathology (Aβ42, Aβ40 and p-tau181) and neurodegeneration (neurofilament light (NFL) and glial fibrillary acidic protein (GFAP)) may identify individuals at risk for both mobility and cognitive impairment and provide novel insights into mechanistic underpinnings.

Method: Blood biomarkers (SiMoA Quanterix N4PE, p-tau181 single-plex) were available in a subsample of 1751 ARIC study participants at Visit 5 (V5, 2011-13, mean age 76.

Biomarkers.

Background: Blood-based biomarkers show promise as a noninvasive, inexpensive method for measuring Alzheimer's disease pathology throughout the lifecourse. However, the predictive and classification accuracy of these biomarkers at different stages of the lifecourse and among diverse, community-dwelling populations requires further investigation.

Method: Between 2014 and 2015, 329 dementia-free participants from the Atherosclerosis Risk in Communities Study underwent brain magnetic resonance imaging (MRI) and florbetapir positron emission tomography (PET).

Developing Topics.

Background: Current blood biomarkers of Alzheimer's disease (AD) neuropathology and neurodegeneration include the ratio of amyloid-β 42 to 40 (Aβ42/Aβ40), phosphorylated tau at threonine 181 (p-Tau181), neurofilament light (NfL) and glial fibrillary acidic protein (GFAP). Prior studies have reported that hypertension is cross-sectionally associated with lower levels of Aβ42/Aβ40 and longitudinally associated with faster accumulation of NfL. In this longitudinal investigation, we expanded on prior research by examining whether mid-life blood pressure status was associated with change in AD biomarkers from mid- to late-life.

Developing Topics.

Background: The NIA Health Disparities Research (NIA-HD) Framework organizes factors in four domains (i.e., environmental, sociocultural, behavioral, and biological), which work together over the lifetime to influence health and health disparities.

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.

Associations of Traumatic Brain Injury and Hearing: Results From the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS).

Objective: To examine associations of traumatic brain injury (TBI) with self-reported and clinical measures of hearing function.

Setting: Four US communities.

Participants: A total of 3176 Atherosclerosis Risk in Communities Study participants who attended the sixth study visit in 2016-2017, when hearing was assessed.

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.

A Hearing Intervention and Health-Related Quality of Life in Older Adults: A Secondary Analysis of the ACHIEVE Randomized Clinical Trial.

Importance: Health-related quality of life is a critical health outcome and a clinically important patient-reported outcome in clinical trials. Hearing loss is associated with poorer health-related quality-of-life in older adults.

Objective: To investigate the 3-year outcomes of hearing intervention vs health education control on health-related quality of life.

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).

Effect of hearing intervention on communicative function: A secondary analysis of the ACHIEVE randomized controlled trial.

Background: The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) Study was designed to determine the effects of a best-practice hearing intervention on cognitive decline among community-dwelling older adults. Here, we conducted a secondary analysis of the ACHIEVE Study to investigate the effect of hearing intervention on self-reported communicative function.

Methods: The ACHIEVE Study is a parallel-group, unmasked, randomized controlled trial of adults aged 70-84 years with untreated mild-to-moderate hearing loss and without substantial cognitive impairment.

Effect of Hearing Intervention Versus Health Education Control on Fatigue: A Secondary Analysis of the ACHIEVE Study.

Background: Fatigue is a common complaint among older adults with hearing loss. The impact of addressing hearing loss on fatigue symptoms has not been studied in a randomized controlled trial. In a secondary analysis of the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study, we investigated the effect of hearing intervention versus health education control on 3-year change in fatigue in community-dwelling older adults with hearing loss.

A validation study demonstrating portable motion capture cameras accurately characterize gait metrics when compared to a pressure-sensitive walkway.

Digital quantification of gait can be used to measure aging- and disease-related decline in mobility. Gait performance also predicts prognosis, disease progression, and response to therapies. Most gait analysis systems require large amounts of space, resources, and expertise to implement and are not widely accessible.

Optimizing cutpoints for clinical interpretation of brain amyloid status using plasma p-tau217 immunoassays.

Introduction: We aimed to evaluate clinical interpretation cutpoints for two plasma phosphorylated tau (p-tau)217 assays (ALZpath and Lumipulse) as predictors of amyloid status for implementation in clinical practice.

Methods: Clinical performance of plasma p-tau217 against amyloid positron emission tomography status was evaluated in participants with mild cognitive impairment or mild dementia (n = 427).

Results: Using a one-cutpoint approach (negative/positive), neither assay achieved ≥ 90% in both sensitivity and specificity.

Traumatic brain injury and cognitive change over 30 years among community-dwelling older adults.

Introduction: There is limited evidence regarding the rate of long-term cognitive decline after traumatic brain injury (TBI) among older adults.

Methods: In this prospective cohort study, time-varying TBI was defined by self-report and International Classification of Disease diagnostic codes. Cognitive testing was performed at five visits over 30 years and scores were combined into a global cognition factor score.