Clinical criteria for limbic-predominant age-related TDP-43 encephalopathy.

Limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is highly prevalent in late life and a common co-pathology with Alzheimer's disease neuropathologic change (ADNC). LATE-NC is a slowly progressive, amnestic clinical syndrome. Alternatively, when present with ADNC, LATE-NC is associated with a more rapid course.

Terminally differentiated effector memory T cells associate with cognitive and AD-related biomarkers in an aging-based community cohort.

Background And Purpose: The immune response changes during aging and the progression of Alzheimer's disease (AD) and related dementia (ADRD). Terminally differentiated effector memory T cells (called T) are important during aging and AD due to their cytotoxic phenotype and association with cognitive decline. However, it is not clear if the changes seen in T are specific to AD-related cognitive decline specifically or are more generally correlated with cognitive decline.

Decentralized clinical trials for medications to reduce the risk of dementia: Consensus report and guidance.

Introduction: Recent growth in the functionality and use of technology has prompted an increased interest in the potential for remote or decentralized clinical trials in dementia. There are many potential benefits associated with decentralized medication trials, but we currently lack specific recommendations for their delivery in the dementia field.

Methods: A modified Delphi method engaged an expert panel to develop recommendations for the conduct of decentralized medication trials in dementia prevention.

National Trends of Vascular Risk Factor Control Among Stroke Survivors: From the National Health and Nutrition Examination Survey 2009 to 2020.

Background: Contemporary data describing the national trends on vascular risk factor control among stroke survivors are limited.

Methods And Results: This is a cross-sectional analysis of the National Health and Nutrition Examination Survey cycles 2009 to 2010 to 2017 to March 2020. Adults (≥18 years of age) with a self-reported diagnosis of stroke were identified.

Terminally differentiated effector memory T cells associate with cognitive and AD-related biomarkers in an aging-based community cohort.

Background And Purpose: The immune response changes during aging and the progression of Alzheimer's disease (AD) and related dementia (ADRD). Terminally differentiated effector memory T cells (called TEMRA) are important during aging and AD due to their cytotoxic phenotype and association with cognitive decline. However, it is not clear if the changes seen in T are specific to AD-related cognitive decline specifically or are more generally correlated with cognitive decline.

Alzheimer's disease and inflammatory biomarkers positively correlate in plasma in the UK-ADRC cohort.

Introduction: Protein-based plasma assays provide hope for improving accessibility and specificity of molecular diagnostics to diagnose dementia.

Methods: Plasma was obtained from participants (N = 837) in our community-based University of Kentucky Alzheimer's Disease Research Center cohort. We evaluated six Alzheimer's disease (AD)- and neurodegeneration-related (Aβ40, Aβ42, Aβ42/40, p-tau181, total tau, and NfLight) and five inflammatory biomarkers (TNF𝛼, IL6, IL8, IL10, and GFAP) using the SIMOA-based protein assay platform.

Early Hippocampal Atrophy Is an Important Signal for Clinicians but Not Necessarily a Harbinger of Alzheimer Disease.

Dementia is one of the most formidable health care challenges we face today. Fortunately, there is new hope for patients and clinicians because we are on the verge of anti-β-amyloid (Aβ) therapies to slow disease progression in Alzheimer disease (AD). But these new therapies are far from curative, and many challenges remain related to confounding pathologic processes and mixed disease states.

Multi-Site Cross-Site Inter-Rater and Test-Retest Reliability and Construct Validity of the MarkVCID White Matter Hyperintensity Growth and Regression Protocol.

Background: White matter hyperintensities (WMH) that occur in the setting of vascular cognitive impairment and dementia (VCID) may be dynamic increasing or decreasing volumes or stable over time. Quantifying such changes may prove useful as a biomarker for clinical trials designed to address vascular cognitive-impairment and dementia and Alzheimer's Disease.

Objective: Conducting multi-site cross-site inter-rater and test-retest reliability of the MarkVCID white matter hyperintensity growth and regression protocol.

Exploratory mass spectrometry of cerebrospinal fluid from persons with autopsy-confirmed LATE-NC.

Background: Common neuropathologies associated with dementia include Alzheimer's disease neuropathologic change (ADNC) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Biofluid proteomics provides a window into the pathobiology of dementia and the information from biofluid tests may help guide clinical management.

Methods: Participants were recruited from a longitudinal cohort of older adults at the University of Kentucky AD Research Center.

A neuropathologic feature of brain aging: multi-lumen vascular profiles.

Cerebrovascular pathologies other than frank infarctions are commonly seen in aged brains. Here, we focus on multi-lumen vascular profiles (MVPs), which are characterized by multiple vessel lumens enclosed in a single vascular channel. Little information exists on the prevalence, risk factors, and co-pathologies of MVPs.

Feasibility of Telehealth Occupational Therapy for Behavioral Symptoms of Adults With Dementia: Randomized Controlled Trial.

Importance: Supporting community residency of adults with Alzheimer's disease (AD) is a critical public health initiative. Occupational therapy can contribute to this goal.

Objective: To assess the feasibility of a novel telehealth intervention to support occupational engagement in community-residing people with AD.

White matter hyperintensities influence distal cortical β-amyloid accumulation in default mode network pathways.

Background And Purpose: Cerebral small vessel disease (SVD) has been suggested to contribute to the pathogenesis of Alzheimer's disease (AD). Yet, the role of SVD in potentially contributing to AD pathology is unclear. The main objective of this study was to test the hypothesis that WMHs influence amyloid β (Aβ) levels within connected default mode network (DMN) tracts and cortical regions in cognitively unimpaired older adults.

Estimating random effects in a finite Markov chain with absorbing states: Application to cognitive data.

Finite Markov chains with absorbing states are popular tools for analyzing longitudinal data with categorical responses. The one step transition probabilities can be defined in terms of fixed and random effects but it is difficult to estimate these effects due to many unknown parameters. In this article we propose a three-step estimation method.

Plasma TDP-43 levels are associated with neuroimaging measures of brain structure in limbic regions.

Introduction: We evaluated the relationship between plasma levels of transactive response DNA binding protein of 43 kDa (TDP-43) and neuroimaging (magnetic resonance imaging [MRI]) measures of brain structure in aging.

Methods: Plasma samples were collected from 72 non-demented older adults (age range 60-94 years) in the University of Kentucky Alzheimer's Disease Research Center cohort. Multivariate linear regression models were run with plasma TDP-43 level as the predictor variable and brain structure (volumetric or cortical thickness) measurements as the dependent variable.

Urinary Incontinence in a Community-Based Autopsy Cohort Is Associated with Limbic Predominant Age-Related TDP-43 Encephalopathy Neuropathologic Changes.

Background: Dementia and urinary incontinence (UI) are etiologically complex clinical syndromes. Dementia and UI often occur in the same individuals, but underlying factors connecting them are incompletely understood.

Objective: Query data from a community-based autopsy series to assess pathologies that underlie UI.

When Alzheimer's is LATE: Why Does it Matter?

Recent therapeutic advances provide heightened motivation for accurate diagnosis of the underlying biologic causes of dementia. This review focuses on the importance of clinical recognition of limbic-predominant age-related TDP-43 encephalopathy (LATE). LATE affects approximately one-quarter of older adults and produces an amnestic syndrome that is commonly mistaken for Alzheimer's disease (AD).

Centralizing prescreening data collection to inform data-driven approaches to clinical trial recruitment.

Background: Recruiting to multi-site trials is challenging, particularly when striving to ensure the randomized sample is demographically representative of the larger disease-suffering population. While previous studies have reported disparities by race and ethnicity in enrollment and randomization, they have not typically investigated whether disparities exist in the recruitment process prior to consent. To identify participants most likely to be eligible for a trial, study sites frequently include a prescreening process, generally conducted by telephone, to conserve resources.