Eye Adult Changes in Thought (Eye ACT) Study: Design and Report on the Inaugural Cohort.

Background: Conflicting research on retinal biomarkers of Alzheimer's disease and related dementias (AD/ADRD) is likely related to limited sample sizes, study design, and protocol differences.

Objective: The prospective Eye Adult Changes in Thought (Eye ACT) seeks to address these gaps.

Methods: Eye ACT participants are recruited from ACT, an ongoing cohort of dementia-free, older adults followed biennially until AD/ADRD, and undergo visual function and retinal imaging assessment either in clinic or at home.

How Generalizable Are Findings from a Community-Based Prospective Cohort Study? Extending Estimates from the Adult Changes in Thought Study to Its Source Population.

Background: The Adult Changes in Thought (ACT) study is a cohort of Kaiser Permanente Washington members ages 65+ that began in 1994.

Objective: We wanted to know how well ACT participants represented all older adults in the region, and how well ACT findings on eye disease and its relationship with Alzheimer's disease generalized to all older adults in the Seattle Metropolitan Region.

Methods: We used participation weights derived from pooling ACT and Behavioral Risk Factor Surveillance System (BRFSS) data to estimate prevalences of common eye diseases and their associations with Alzheimer's disease incidence.

Neuropathologic Burden and Dementia in Nonagenarians and Centenarians: Comparison of 2 Community-Based Cohorts.

Background And Objectives: The aim of this study was to compare 2 large clinicopathologic cohorts of participants aged 90+ and to determine whether the association between neuropathologic burden and dementia in these older groups differs substantially from those seen in younger-old adults.

Methods: Autopsied participants from The 90+ Study and Adult Changes in Thought (ACT) Study community-based cohort studies were evaluated for dementia-associated neuropathologic changes. Associations between neuropathologic variables and dementia were assessed using logistic or linear regression, and the weighted population attributable fraction (PAF) per type of neuropathologic change was estimated.

Cognitively defined Alzheimer's dementia subgroups have distinct atrophy patterns.

Introduction: We sought to determine structural magnetic resonance imaging (MRI) characteristics across subgroups defined based on relative cognitive domain impairments using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and to compare cognitively defined to imaging-defined subgroups.

Methods: We used data from 584 people with Alzheimer's disease (AD) (461 amyloid positive, 123 unknown amyloid status) and 118 amyloid-negative controls. We used voxel-based morphometry to compare gray matter volume (GMV) for each group compared to controls and to AD-Memory.

Ceiling effects and differential measurement precision across calibrated cognitive scores in the Framingham Study.

Objective: To calibrate cognitive assessment data across multiple waves of the Framingham Heart Study (FHS), addressing study design considerations, ceiling effects, and measurement precision.

Method: FHS participants completed several cognitive assessments including screening instruments and more comprehensive batteries at different study visits. We used expert opinion to assign each cognitive test item to a single domain-memory, executive function, language, visuospatial abilities, or none of the above.

Association of Traumatic Brain Injury with Late Life Neuropathological Outcomes in a Community-Based Cohort.

Background: Prior studies into the association of head trauma with neuropathology have been limited by incomplete lifetime neurotrauma exposure characterization.

Objective: To investigate the neuropathological sequelae of traumatic brain injury (TBI) in an autopsy sample using three sources of TBI ascertainment, weighting findings to reflect associations in the larger, community-based cohort.

Methods: Self-reported head trauma with loss of consciousness (LOC) exposure was collected in biennial clinic visits from 780 older adults from the Adult Changes in Thought study who later died and donated their brain for research.

Investigation of the association of military employment and Parkinson's disease with a validated Parkinson's disease case-finding strategy.

Introduction: Persons with military involvement may be more likely to have Parkinson's disease (PD) risk factors. As PD is rare, case finding remains a challenge, contributing to our limited understanding of PD risk factors. Here, we explore the validity of case-finding strategies and whether military employment is associated with PD.

Shifting of Cognitive Assessments Between Face-to-Face and Telephone Administration: Measurement Considerations.

Objectives: Telephone-administered cognitive assessments are a cost-effective and sometimes necessary alternative to face-to-face assessments. There is limited information in large studies concerning mode effects, or differences in cognition attributable to the assessment method, as a potential measurement threat. We evaluated mode effects on cognitive scores using a population-based sample of community-living older adults.

Harmonizing the preclinical Alzheimer cognitive composite for multicohort studies.

Objectives: Studies are increasingly examining research questions across multiple cohorts using data from the preclinical Alzheimer cognitive composite (PACC). Our objective was to use modern psychometric approaches to develop a harmonized PACC.

Method: We used longitudinal data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), Harvard Aging Brain Study (HABS), and Australian Imaging, Biomarker and Lifestyle Study of Ageing (AIBL) cohorts ( = 2,712).

Association Between Cataract Extraction and Development of Dementia.

Importance: Visual function is important for older adults. Interventions to preserve vision, such as cataract extraction, may modify dementia risk.

Objective: To determine whether cataract extraction is associated with reduced risk of dementia among older adults.

Association of Performance on Dichotic Auditory Tests With Risk for Incident Dementia and Alzheimer Dementia.

Importance: Age-related hearing difficulties can include problems with signal audibility and central auditory processing. Studies have demonstrated associations between audibility and dementia risk. To our knowledge, limited data exist to determine whether audibility, central processing, or both drive these associations.

Association of Military Employment With Late-Life Cognitive Decline and Dementia: A Population-Based Prospective Cohort Study.

Introduction: As the number of U.S. veterans over age 65 has increased, interest in whether military service affects late-life health outcomes has grown.

Longitudinal cognitive performance of Alzheimer's disease neuropathological subtypes.

Introduction: Alzheimer's disease (AD) neuropathological subtypes (limbic predominant [lpAD], hippocampal sparing [HpSpAD], and typical [tAD]), defined by relative neurofibrillary tangle (NFT) burden in limbic and cortical regions, have not been studied in prospectively characterized epidemiological cohorts with robust cognitive assessments.

Methods: Two hundred ninety-two participants with neuropathologically confirmed AD from the Religious Orders Study and Memory and Aging Project were categorized by neuropathological subtype based on previously specified diagnostic criteria using quantitative regional NFT counts. Rates of cognitive decline were compared across subtypes using linear mixed-effects models that included subtype, time, and a subtype-time interaction as predictors and four cognitive domain factor scores (memory, executive function, language, visuospatial) and a global score as outcomes.

Leveraging Neuroimaging Tools to Assess Precision and Accuracy in an Alzheimer's Disease Neuropathologic Sampling Protocol.

Introduction: The study of Alzheimer's disease investigates topographic patterns of degeneration in the context of connected networks comprised of functionally distinct domains using increasingly sophisticated molecular techniques. Therefore, obtaining high precision and accuracy of neuropathologic tissue sampling will enhance the reliability of molecular studies and contribute to the understanding of Alzheimer's disease pathology. Neuroimaging tools can help assess these aspects of current sampling protocols as well as contribute directly to their improvement.

Alzheimer's Disease-Related Neuropathology Among Patients with Medication Treated Type 2 Diabetes in a Community-Based Autopsy Cohort.

Background: Diabetes is a risk factor for Alzheimer's disease and related dementias (ADRD). Epidemiologic evidence shows an association between diabetes medications and ADRD risk; cell and mouse models show diabetes medication association with AD-related neuropathologic change (ADNC).

Objective: This hypothesis-generating analysis aimed to describe autopsy-measured ADNC for individuals who used diabetes medications.

Association of Lifetime TBI and Military Employment with Late Life ADL Functioning: A Population-Based Prospective Cohort Study.

Objective: To determine associations of traumatic brain injury (TBI) and military employment with activities of daily living (ADL) in late life.

Design: Population-based prospective cohort study with biennial follow-up and censoring at the time of dementia diagnosis.

Setting: Community-based integrated health care delivery system.

The Delayed Neuropathological Consequences of Traumatic Brain Injury in a Community-Based Sample.

The late neuropathological effects of traumatic brain injury have yet to be fully elucidated, particularly with respect to community-based cohorts. To contribute to this critical gap in knowledge, we designed a multimodal neuropathological study, integrating traditional and quantitative approaches to detect pathologic changes in 532 consecutive brain autopsies from participants in the Adult Changes in Thought (ACT) study. Diagnostic evaluation including assessment for chronic traumatic encephalopathy (CTE) and quantitative immunoassay-based methods were deployed to examine levels of pathological (hyperphosphorylated) tau (pTau) and amyloid (A) β in brains from ACT participants with ( = 107) and without ( = 425) history of remote TBI with loss of consciousness (w/LOC).

Associations Between Retinal Artery/Vein Occlusions and Risk of Vascular Dementia.

Background: Vascular disease is a risk factor for Alzheimer's disease (AD) and related dementia in older adults. Retinal artery/vein occlusion (RAVO) is an ophthalmic complication of systemic vascular pathology. Whether there are associations between RAVO and dementia risk is unknown.

Impact of COVID-19 'Stay Home, Stay Healthy' Orders on Function among Older Adults Participating in a Community-Based, Behavioral Intervention Study.

Early mitigation orders for COVID-19 halted participation in community-based programs. We examined the early impact of "Stay Home, Stay Healthy" orders on functioning in older adults participating in a behavioral intervention study involving community-based exercise. A quasi-natural experiment, using mixed methods ( = 39).

Association of remote traumatic brain injury and military employment with late-life trajectories of depressive symptom severity.

Background: Traumatic brain injury (TBI) and military service are common lifetime exposures among current older adults that may affect late-life mental health. The objective of the present study was to evaluate the association between TBI with loss of consciousness (LOC) and military employment and late-life depressive symptom severity trajectory.

Methods: 1445 males and 2096 females adults at least 65 years old without dementia or recent TBI were enrolled and followed biennially for up to 10 years in the Adult Changes in Thought study from Kaiser Permanente Washington in Seattle, Washington.

Development and validation of language and visuospatial composite scores in ADNI.

Introduction: Composite scores may be useful to summarize overall language or visuospatial functioning in studies of older adults.

Methods: We used item response theory to derive composite measures for language (ADNI-Lan) and visuospatial functioning (ADNI-VS) from the cognitive battery administered in the Alzheimer's Disease Neuroimaging Initiative (ADNI). We evaluated the scores among groups of people with normal cognition, mild cognitive impairment (MCI), and Alzheimer's disease (AD) in terms of responsiveness to change, association with imaging findings, and ability to differentiate between MCI participants who progressed to AD dementia and those who did not progress.