Biomarkers.

Background: Stiffening of the large elastic arteries is an emerging age-related risk factor for Alzheimer's disease (AD) and related dementia (ADRD). Arterial stiffness is associated with pathological changes underlying AD/ADRD, and total arterial stiffness (T-PWV) can be subdivided into two main mechanisms. Structural stiffening (S-PWV) is due to intrinsic remodeling of the artery wall, and load-dependent stiffening (LD-PWV) is due to increased blood pressure without intrinsic changes to the artery wall.

Biomarkers.

Background: Age-related neurodegenerative disorders (NDDs) continuum includes late-onset Alzheimer's disease (LOAD), Dementia with Lewy bodies (DLB), and Parkinson's disease (PD) exhibit shared and distinct clinicopathological characteristics. Each of the different NDDs is characterized by a complex genetic etiology and although numerous loci have been identified via GWAS, and the causal genes and the specific neuronal and glial cell subtypes through which they exert their pathogenic effects are yet to be fully elucidated. We aimed to untangle the genetic complexity of NDDs, and to identify shared and distinct biological pathways and disease driver cell-subtypes across NDDs.

Biomarkers.

Background: Synuclein Aggregate Assays (SAA) in cerebrospinal fluid (CSF) and in skin biopsy have been shown to successfully identify underlying synuclein (Lewy body) pathology in patients with Parkinson's disease. Data in Lewy Body Dementia (LBD) is limited, particularly with pathologic confirmation and staging of underlying Lewy body pathology, and other co-pathologies.

Method: Utilizing data and biofluids from participants in the U.

Biomarkers.

Background: Postoperative delirium (POD) is characterized by fluctuating attention after surgery and is associated with increased risk of developing Alzheimer's Disease (AD). While the neurophysiological changes that underlie POD and increased risk of AD are unclear, recent data has raised the possibility that an exaggerated brain response to anesthetics may be a biomarker for POD risk and preclinical AD-like pathology. Thus, we examined whether anesthetic-dose-adjusted intraoperative brain activity is associated with POD or preoperative brain vulnerabilities (preclinical AD-like pathology, preoperative inattention) that may contribute to risk of POD (and later AD).

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: The National Institute on Aging (NIA) and the Alzheimer's Association (AA) recently updated their 2018 recommendations for the diagnosis and characterization of Alzheimer's disease (AD), which include the use of blood-based biomarkers (BBMs) for the differential diagnosis of AD. BBMs of amyloid-beta, phosphorylated tau, neurodegeneration, inflammation, and alpha-synuclein were defined, with a highlighted need for blood biomarkers of vascular brain injury. Many questions remain regarding how to implement these biomarkers for clinical care including diagnosis and to assess eligibility for disease modifying treatments (DMT).

Biomarkers.

Background: Metabolic syndrome (MetS) was associated with an increased incidence of mild cognitive impairment (MCI) and progression to dementia. However, little is known about why this occurs. This study was to examine the correlation between the MetS indicators and cerebrospinal fluid (CSF) pathological protein biomarkers to investigate this mechanism.

Biomarkers.

Background: Alzheimer's disease is associated with neurotoxic amyloid-beta (Aβ) plaques. Studies in mice demonstrated that cerebrospinal fluid (CSF) clearance, if impaired, reduces Aβ clearance by 70% and that sleep enhances CSF clearance via expanding extracellular space by 60%. However, the impact of sleep on extracellular volume in human remains unclear due to lack of non-invasive technology.

Biomarkers.

Background: Less adequate cardiorespiratory fitness (CRF) is associated with several aspects of Alzheimer's disease (AD) pathology, including neuroinflammation, neurodegeneration and synaptic dysfunction, all of which are known contributors to the clinical outcome - progressive cognitive decline [1]. AD-associated biomolecular changes also seem to be attenuated in carriers of the functionally advantageous variant of the KLOTHO gene (KL-VS) [2]. While KL-VS and CRF both appear to mitigate aspects of AD pathology, they have been exclusively studied in isolation.

Biomarkers.

Background: Studies suggest that approximately 60 to 70 percent of the variability observed in cognitive abilities during aging can be attributed to genetic factors. Therefore, investigating the longitudinal multiomics changes associated with alterations in cognitive measures, such as the Mini-Mental State Examination (MMSE) score, is of utmost importance.

Method: Longitudinal changes in gene and protein expression related to MMSE scores were examined in the Cameron County Hispanic Cohort (CCHC), an extensively phenotyped, randomly-recruited, cohort of Mexican Americans residing at the US-Mexico border.

Biomarkers.

Background: Phosphorylated tau (p-tau) 181 was isolated in aqueous humor and was correlated with other measures that might be consistent with Alzheimer's disease (AD) including higher plasma p-tau181 concentrations and lower Montreal Cognitive Assessment (MoCA blind version 7.1) scores.

Method: Blood samples, aqueous humor samples, and MoCA scores were collected from patients at the time of cataract surgery.

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: Subjective cognitive decline (SCD), or a person's perception of changes in their cognitive abilities, has been identified as a possible early marker of preclinical Alzheimer's disease (AD) in non-Hispanic Whites; however, research is lacking about the clinical utility of SCD in diverse populations. This study investigated the associations of self and informant reports of SCD, plasma biomarker profiles of AD, and objective cognitive performance in Hispanic older adults living in Miami.

Method: Hispanic participants enrolled in the 1Florida Alzheimer's Disease Research Center who completed neuropsychological testing and blood draws for biomarker analysis were eligible.

Biomarkers.

Background: Dys-connectivity has been repeatedly shown in Alzheimer's Disease (AD) but the change of connectivity gradient across the brain is under-studied. In this study, we used resting state fMRI (rsfMRI) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to build a whole brain functional connectivity matrix. We then compared the major connectivity gradients decomposed from the connectivity matrix from normal controls (NC), mild cognitive impairment (MCI), and AD patients.

Biomarkers.

Background: Aging is the strongest risk factor for Alzheimer's disease (AD). Accordingly, identifying biomarkers of accelerated aging is a major focus of AD prevention research. Current MRI-based "aging clocks" (i.

Biomarkers.

Background: The Parkinson's disease (PD) cognition-related covariance pattern (PDCP) was derived from network analysis of metabolic positron emission tomography (PET). The expression score is a feasible imaging biomarker that correlates with neuropsychological test performance. Graph analysis within specific networks characterizes brain function, particularly in terms of assortativity, which reflects the tendency to connect to nodes with similar degree values.

Biomarkers.

Background: Cognitively unimpaired (CU) older adults with abnormal levels of β-amyloid (Aβ) deposition are considered in the preclinical stage of Alzheimer's disease (AD) and, when combined with the subjective cognitive decline (SCD), are proposed as the stage 2 AD in the NIA-AA framework. Here, we aim to investigate whether neuropathologic deterioration increases in early stages, particularly in stage 2 AD.

Method: We included 341 CU participants over 50 years of age from the Sino Longitudinal Study on Cognitive Decline (SILCODE) study.

Biomarkers.

Background: Amyloid-b deposition and tau tangle formation are the key pathologies of Alzheimer's disease (AD). The presence of these pathologies in cerebrospinal fluid (CSF) biomarkers is used for a biological diagnosis of AD. It remains unclear how the prevalence of AT biomarker profiles depends on apolipoprotein E (APOE) genotype.

Biomarkers.

Background: Worse sleep is associated with a greater risk of Alzheimer's disease (AD). However, few studies have linked objective sleep with neuroimaging outcomes, limiting our understanding of how poor sleep impacts the brain. The U.

Biomarkers.

Background: Since 2012, many groups have been using immunomagnetic reduction (IMR) for assaying plasma amyloid β 1-40 (Aβ) peptide, Aβ peptide and total tau protein (T-Tau) in cognitively normal controls (NC) and patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease dementia (ADD). Tremendous results have been independently reported. In this work, we summarize the reported levels of plasma Aβ, Aβ and T-Tau to investigate the consistence among studies.

Biomarkers.

Background: Metabolomics captures net influences of exposome, diet, gut microbiome, and genome, informing about individuality and how we respond to interventions. Applications of metabolomics in pharmacology are starting to enable a Systems Pharmacology approach, where the outcome of a treatment is considered to evolve from effects on complex molecular networks, enabling insights into response variations. We bring the power of these approaches to the study of the MIND, a Mediterranean DASH diet for prevention of cognitive decline.

Biomarkers.

Background: The G protein-coupled receptor GPR39 is heavily associated with the pathogenesis of neurologic disorders, including Alzheimer's disease (AD) and related dementia (ADRD). Its dysregulation of zinc 2+ (Zn) processes triggers metallic dyshomeostasis, oxidative stress, neuroinflammation, microtubule destabilization, synaptic dysfunction, and tau phosphorylation-all hallmarks of neurodegeneration. Hence, pharmacologic modulation of GPR39 could offer an effective treatment against AD and ADRD.

Biomarkers.

Background: Detecting functional performance decline from normal aging to dementia is critical for early detection and intervention. The informant-based A-IADL-Q-SV has been demonstrated with good psychometric properties. The aims of this study were to: (1) translate, culturally adapt, and validate the Traditional Chinese version of the A-IADL-Q-SV-TC for Taiwanese; (2) evaluate the psychometric properties.

Biomarkers.

Background: The aim of this study was to identify a gut microbial signature associated with patterns of gray matter volume in AD, and to validate the microbial signature by testing it against measures of AD pathology and cognitive performance. Prior literature suggests that microbial species involved in bile acid production and inflammation may be implicated in the microbial signature.

Method: The sample comprised 204 Microbiome in Alzheimer's Risk Study participants (22 AD, 10 MCI, and 172 CN; 129 Females, 78 APOE+) from the Wisconsin Alzheimer's Disease Research Center and Wisconsin Registry for Alzheimer's Prevention.

Biomarkers.

Background: Increasingly, research participants in Alzheimer's studies are seeking disclosure of research results. However, there are no guidelines for result disclosure and specifically, few studies report on their biomarker disclosure procedure. The Duke/UNC ADRC seeks to disclose research results to participants in a standardized fashion with high participant satisfaction.