Digital Commons Network^™

The Relationship Of Trait-Like Compassion With Epigenetic Aging: The Population-Based Prospective Young Finns Study, Henrik Dobewall, Liisa Keltikangas-Järvinen, Saara Marttila, Pashupati P Mishra, Aino Saarinen, C Robert Cloninger, Igor Zwir, Mika Kähönen, Mikko Hurme, Olli Raitakari, Terho Lehtimäki, Mirka Hintsanen

2020-Current year OA Pubs

INTRODUCTION: Helping others within and beyond the family has been related to living a healthy and long life. Compassion is a prosocial personality trait characterized by concern for another person who is suffering and the motivation to help. The current study examines whether epigenetic aging is a potential biological mechanism that explains the link between prosociality and longevity.

METHODS: We used data from the Young Finns Study that follows six birth-cohorts from age 3-18 to 19-49. Trait-like compassion for others was measured with the Temperament and Character Inventory in the years 1997 and 2001. Epigenetic age acceleration and telomere length …

Plasma And Cerebrospinal Fluid Proteomic Signatures Of Acutely Sleep-Deprived Humans: An Exploratory Study, Ana Vaquer-Alicea, Jinsheng Yu, Haiyan Liu, Brendan P Lucey

2020-Current year OA Pubs

STUDY OBJECTIVES: Acute sleep deprivation affects both central and peripheral biological processes. Prior research has mainly focused on specific proteins or biological pathways that are dysregulated in the setting of sustained wakefulness. This exploratory study aimed to provide a comprehensive view of the biological processes and proteins impacted by acute sleep deprivation in both plasma and cerebrospinal fluid (CSF).

METHODS: We collected plasma and CSF from human participants during one night of sleep deprivation and controlled normal sleep conditions. One thousand and three hundred proteins were measured at hour 0 and hour 24 using a high-scale aptamer-based proteomics platform (SOMAscan) …

Gene-Educational Attainment Interactions In A Multi-Population Genome-Wide Meta-Analysis Identify Novel Lipid Loci, Lisa De Las Fuentes, Karen L. Schwander, Yun Ju Sung, Mary F. Feitosa, Ahn Do, C. Charles Gu, Treva K. Rice, Mary K. Wojczynski, Michael M. Province, Dabeeru C. Rao, Et Al.

2020-Current year OA Pubs

No abstract provided.

Transferability Of Alzheimer Disease Polygenic Risk Score Across Populations And Its Association With Alzheimer Disease-Related Phenotypes, Sang-Hyuk Jung, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Polygenic risk scores (PRSs), which aggregate the genetic effects of single-nucleotide variants identified in genome-wide association studies (GWASs), can help distinguish individuals at a high genetic risk for Alzheimer disease (AD). However, genetic studies have predominantly focused on populations of European ancestry.

OBJECTIVE: To evaluate the transferability of a PRS for AD in the Korean population using summary statistics from a prior GWAS of European populations.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study developed a PRS based on the summary statistics of a large-scale GWAS of a European population (the International Genomics of Alzheimer Project; 21 982 AD cases …

Association Of Leukocyte Telomere Length With Perceived Physical Fatigability, Rain Katz, Emma L Gay, Allison L Kuipers, Joseph H Lee, Lawrence S Honig, Kaare Christensen, Mary F Feitosa, Mary K Wojczynski, Nancy W Glynn, Llfs Research Group

2020-Current year OA Pubs

BACKGROUND: Leukocyte telomere length (LTL) is a potential genomic marker of biological aging, but its relation to fatigability, a prognostic indicator of phenotypic aging (e.g., functional decline) is unknown. We hypothesized shorter LTL would predict greater perceived physical fatigability, but that this association would be attenuated by adjusting for chronological age.

METHODS: Two generations of participants (N = 1997; 309 probands, 1688 offspring) were from the Long Life Family Study (age = 73.7 ± 10.4, range 60-108, 54.4 % women), a longitudinal cohort study of aging. LTL was assayed at baseline. Perceived physical fatigability was measured 8.0 ± 1.1 years …

Vascular Endothelial-Cadherin As A Marker Of Endothelial Injury In Preclinical Alzheimer Disease, Rawan Tarawneh, Rachel S Kasper, Jessie Sanford, Chia-Ling Phuah, Jason Hassenstab, Carlos Cruchaga

2020-Current year OA Pubs

OBJECTIVE: Endothelial dysfunction is an early and prevalent pathology in Alzheimer disease (AD). We here investigate the value of vascular endothelial-cadherin (VEC) as a cerebrospinal fluid (CSF) marker of endothelial injury in preclinical AD.

METHODS: Cognitively normal participants (Clinical Dementia Rating [CDR] 0) from the Knight Washington University-ADRC were included in this study (n = 700). Preclinical Alzheimer's Cognitive Composite (PACC) scores, CSF VEC, tau, p-tau181, Aβ42/Aβ40, neurofilament light-chain (NFL) levels, and magnetic resonance imaging (MRI) assessments of white matter injury (WMI) were obtained from all participants. A subset of participants underwent brain amyloid imaging using positron emission tomography (amyloid-PET) …

Oxidative Stress-Induced Cellular Senescence In Aging Retina And Age-Related Macular Degeneration, Ryo Terao, Tazbir Ahmed, Ayana Suzumura, Hiroko Terasaki

2020-Current year OA Pubs

Aging leads to a gradual decline of function in multiple organs. Cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD) are age-related ocular diseases. Because their pathogenesis is unclear, it is challenging to combat age-related diseases. Cellular senescence is a cellular response characterized by cell cycle arrest. Cellular senescence is an important contributor to aging and age-related diseases through the alteration of cellular function and the secretion of senescence-associated secretory phenotypes. As a driver of stress-induced premature senescence, oxidative stress triggers cellular senescence and age-related diseases by inducing senescence markers via reactive oxygen species and mitochondrial dysfunction. In this review, …

Disease Burden Affects Aging Brain Function, Lori L Beason-Held, Danielle Fournier, Andrea T Shafer, Elisa Fabbri, Yang An, Chiung-Wei Huang, Murat Bilgel, Dean F Wong, Luigi Ferrucci, Susan M Resnick

2020-Current year OA Pubs

BACKGROUND: Most older adults live with multiple chronic disease conditions, yet the effect of multiple diseases on brain function remains unclear.

METHODS: We examine the relationship between disease multimorbidity and brain activity using regional cerebral blood flow (rCBF) 15O-water PET scans from 97 cognitively normal participants (mean baseline age 76.5) in the Baltimore Longitudinal Study of Aging (BLSA). Multimorbidity index scores, generated from the presence of 13 health conditions, were correlated with PET data at baseline and in longitudinal change (n = 74) over 5.05 (2.74 SD) years.

RESULTS: At baseline, voxel-based analysis showed that higher multimorbidity scores were associated …

World Guidelines For Falls Prevention And Management For Older Adults: A Global Initiative, Manuel Montero-Odasso, Susan Stark, Et Al.

2020-Current year OA Pubs

No abstract provided.

Improving Our Understanding Of Driving Changes In Preclinical And Early Symptomatic Alzheimer's Disease: The Role Of Naturalistic Driving Studies, Catherine M Roe

2020-Current year OA Pubs

Research on how preclinical and early symptomatic Alzheimer's disease (AD) impacts driving behavior is in its infancy, with several important research areas yet to be explored. This paper identifies research gaps and suggests priorities for driving studies over the next few years among those at the earliest stages of AD. These priorities include how individual differences in demographic and biomarker measures of AD pathology, as well as differences in the in-vehicle and external driving environment, affect driving behavior. Understanding these differences is important to developing future interventions to increase driving safety among those at the earliest stages of AD.

Age-Dependent White Matter Disruptions After Military Traumatic Brain Injury: Multivariate Analysis Results From Enigma Brain Injury, Heather C Bouchard, Paul M Thompson, Aristeidis Sotiras, Et Al.

2020-Current year OA Pubs

Mild Traumatic brain injury (mTBI) is a signature wound in military personnel, and repetitive mTBI has been linked to age-related neurogenerative disorders that affect white matter (WM) in the brain. However, findings of injury to specific WM tracts have been variable and inconsistent. This may be due to the heterogeneity of mechanisms, etiology, and comorbid disorders related to mTBI. Non-negative matrix factorization (NMF) is a data-driven approach that detects covarying patterns (components) within high-dimensional data. We applied NMF to diffusion imaging data from military Veterans with and without a self-reported TBI history. NMF identified 12 independent components derived from fractional …

An International Analysis Evaluating Frontline Bendamustine With Rituximab In Extranodal Marginal Zone Lymphoma, Juan Pablo Alderuccio, Marcus P Watkins, Raya Saba, Brad S Kahl, Et Al

Open Access Publications

Extranodal marginal zone lymphoma (EMZL) is a heterogeneous non-Hodgkin lymphoma. No consensus exists regarding the standard-of-care in patients with advanced-stage disease. Current recommendations are largely adapted from follicular lymphoma, for which bendamustine with rituximab (BR) is an established approach. We analyzed the safety and efficacy of frontline BR in EMZL using a large international consortium. We included 237 patients with a median age of 63 years (range, 21-85). Most patients presented with Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (n = 228; 96.2%), stage III/IV (n = 179; 75.5%), and intermediate (49.8%) or high (33.3%) Mucosa Associated …

Effect Of Aerobic Or Resistance Exercise, Or Both, On Intermuscular And Visceral Fat And Physical And Metabolic Function In Older Adults With Obesity While Dieting, Debra L Waters, Lina Aguirre, Burke Gurney, David R Sinacore, Kenneth Fowler, Giulia Gregori, Reina Armamento-Villareal, Clifford Qualls, Dennis T Villareal

2020-Current year OA Pubs

BACKGROUND: Obesity exacerbates age-related effects on body composition and physical and metabolic function. Which exercise mode is most effective in mitigating these deleterious changes in dieting older adults with obesity is unknown.

METHODS: In a randomized controlled trial, we performed a head-to-head comparison of aerobic (AEX), resistance (REX), or combination (COMB) exercise during matched ~10% weight loss in 160 obese older adults. Prespecified analyses compared 6-month changes in intermuscular adipose tissue (IMAT) and visceral adipose tissue (VAT) assessed using MRI, insulin sensitivity index (ISI) by oral glucose tolerance test, physical function using Modified Physical Performance Test (PPT), VO2peak, gait speed, …

Perceived Physical Fatigability Predicts All-Cause Mortality In Older Adults, Nancy W. Glynn, Theresa Gmelin, Sharon W. Renner, Yujia Susanna Qiao, Robert M. Boudreau, Mary F. Feitosa, Mary K. Wojczynski, Stephanie Cosentino, Stacy L. Andersen, Kaare Christensen, Anne B. Newman

Open Access Publications

BACKGROUND: Perceived physical fatigability is highly prevalent in older adults and associated with mobility decline and other health consequences. We examined the prognostic value of perceived physical fatigability as an independent predictor of risk of death among older adults.

METHODS: Participants (N = 2 906), mean age 73.5 [SD, 10.4] years, 54.2% women, 99.7% white enrolled in the Long Life Family Study, were assessed at Visit 2 (2014-2017) with 2.7 [SD, 1.0] years follow-up. The Pittsburgh Fatigability Scale (PFS), a 10-item, self-administered validated questionnaire (score range 0-50, higher = greater fatigability) measured perceived physical fatigability at Visit 2. Deaths post-Visit …

High Temporal Resolution Measurements Of Movement Reveal Novel Early-Life Physiological Decline In C. Elegans, Drew Benjamin Sinha, Zachary Scott Pincus

Open Access Publications

Age-related physiological changes are most notable and best-studied late in life, while the nature of aging in early- or middle-aged individuals has not been explored as thoroughly. In C. elegans, many studies of movement vs. age generally focus on three distinct phases: sustained, youthful movement; onset of rapidly progressing impairment; and gross immobility. We investigated whether this first period of early-life adult movement is a sustained "healthy" level of high function followed by a discrete "movement catastrophe"-or whether there are early-life changes in movement that precede future physiological declines. To determine how movement varies during early adult life, we followed …

The 2021 Faseb Science Research Conference On Nad Metabolism And Signaling, Vera Gorbunova, Shin-Ichiro Imai, Et Al

Open Access Publications

No abstract provided.

What Can Brinley Plots Tell Us About Cognitive Aging? Exploring Simulated Data And Modified Brinley Plots, Jessica Nicosia, Emily R Cohen-Shikora, Michael J Strube

Open Access Publications

Cognitive aging researchers have been challenged with demonstrating age-related effects above and beyond global slowing ever since Cerella raised this issue in 1990. As the literature has made clear, this has indeed proved to be a difficult task and continues to plague the field. One way that researchers have attempted to test for disproportionate age differences across task conditions is by using Brinley plots, or plotting the mean response latencies of older adults against the mean latencies for younger adults. The simplicity and large proportion of variance accounted for by these models has led to the widespread use of Brinley …

Nia Long Life Family Study: Objectives, Design, And Heritability Of Cross-Sectional And Longitudinal Phenotypes, Mary K. Wojczynski, Shiow Jiuan Lin, Paola Sebastiani, Thomas T. Perls, Joseph Lee, Alexander Kulminski, Anne Newman, Joe M. Zmuda, Kaare Christensen, Michael A. Province

Open Access Publications

The NIA Long Life Family Study (LLFS) is a longitudinal, multicenter, multinational, population-based multigenerational family study of the genetic and nongenetic determinants of exceptional longevity and healthy aging. The Visit 1 in-person evaluation (2006-2009) recruited 4 953 individuals from 539 two-generation families, selected from the upper 1% tail of the Family Longevity Selection Score (FLoSS, which quantifies the degree of familial clustering of longevity). Demographic, anthropometric, cognitive, activities of daily living, ankle-brachial index, blood pressure, physical performance, and pulmonary function, along with serum, plasma, lymphocytes, red cells, and DNA, were collected. A Genome Wide Association Scan (GWAS) (Ilumina Omni 2.5M …

Weakly Activated Core Neuroinflammation Pathways Were Identified As A Central Signaling Mechanism Contributing To The Chronic Neurodegeneration In Alzheimer's Disease, Fuhai Li, Abdallah M Eteleeb, William Buchser, Christopher Sohn, Guoqiao Wang, Chengjie Xiong, Philip R Payne, Eric Mcdade, Celeste M Karch, Oscar Harari, Carlos Cruchaga

2020-Current year OA Pubs

OBJECTIVES: Neuroinflammation signaling has been identified as an important hallmark of Alzheimer's disease (AD) in addition to amyloid β plaques (Aβ) and neurofibrillary tangles (NFTs). However, the molecular mechanisms and biological processes of neuroinflammation remain unclear and have not well delineated using transcriptomics data available. Our objectives are to uncover the core neuroinflammation signaling pathways in AD using integrative network analysis on the transcriptomics data.

MATERIALS AND METHODS: From a novel perspective, i.e., investigating weakly activated molecular signals (rather than the strongly activated molecular signals), we developed integrative and systems biology network analysis to uncover potential core neuroinflammation signaling targets …

Development And Implementation Of An Electronic Clinical Dementia Rating And Financial Capacity Instrument-Short Form, Taylor Howell, John C Morris, Krista L Moulder, Connie Mayo, Maria Carroll, Yan Li, Et Al

2020-Current year OA Pubs

Introduction: To address the need for remote assessments of cognitive decline and dementia, we developed and administered electronic versions of the Clinical Dementia Rating (CDR®) and the Financial Capacity Instrument-Short Form (FCI-SF) (F-CAP

Methods: The CDR and FCI-SF were adapted for remote, unsupervised, online use based on item response analysis of the standard instruments. Participants completed the eCDR and eFCI first in clinic, and then at home within 2 weeks.

Results: Of the 243 enrolled participants, 179 (73%) cognitively unimpaired (CU), 50 (21%) with mild cognitive impairment (MCI) or dementia, and 14 (6%) with an unknown diagnosis, 84% and 85% …

Investing In Late-Life Brain Capital, Walter D Dawson, Eric J Lenze, Et Al.

2020-Current year OA Pubs

Within many societies and cultures around the world, older adults are too often undervalued and underappreciated. This exacerbates many key challenges that older adults may face. It also undermines the many positive aspects of late life that are of tremendous value at both an individual and societal level. We propose a new approach to elevate health and well-being in late life by optimizing late-life Brain Capital. This form of capital prioritizes brain skills and brain health in a brain economy, which the challenges and opportunities of the 21st-century demands. This approach incorporates investing in late-life Brain Capital, developing initiatives focused …

Driving Performance In Older Adults: Current Measures, Findings, And Implications For Roadway Safety, Robert Toups, Theresa J Chirles, Johnathon P Ehsani, Jeffrey P Michael, John P K Bernstein, Matthew Calamia, Thomas D Parsons, David B Carr, Jeffrey N Keller

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Over 10,000 people a day turn 65 in the United States. For many older adults, driving represents an essential component of independence and is one of the most important factors in overall mobility. Recent survey studies in older adults suggest that up to 60% of older adult drivers with mild cognitive impairment, and up to 30% with dementia, continue to drive. The purpose of this review is to provide a comprehensive and detailed resource on the topics of cognition and driving for clinicians, researchers, and policymakers working on efforts related to older adult drivers.

RESEARCH DESIGN AND …

Associations Of Polymorphisms In The Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease: An Individual-Level Meta-Analysis, Tessa Schillemans, Sharon Cresci, Et Al

2020-Current year OA Pubs

No abstract provided.

Friends And Foes: Extracellular Vesicles In Aging And Rejuvenation, Brian V Lananna, Shin-Ichiro Imai

2020-Current year OA Pubs

Extracellular vesicles (EVs) are released by many different cell types throughout the body and play a role in a diverse range of biological processes. EVs circulating in blood as well as in other body fluids undergo dramatic alterations over an organism's lifespan that are only beginning to be elucidated. The exact nature of these changes is an area of active and intense investigation, but lacks clear consensus due to the substantial heterogeneity in EV subpopulations and insufficiencies in current technologies. Nonetheless, emerging evidence suggests that EVs regulate systemic aging as well as the pathophysiology of age-related diseases. Here, we review …

Brain White Matter Structure And Amyloid Deposition In Black And White Older Adults: The Aric-Pet Study, Keenan A Walker, Noah Silverstein, Yun Zhou, Timothy M Hughes, Clifford R Jack, David S Knopman, A Richey Sharrett, Dean F Wong, Thomas H Mosley, Rebecca F Gottesman

Open Access Publications

Background White matter abnormalities are a common feature of aging and Alzheimer disease, and tend to be more severe among Black individuals. However, the extent to which white matter abnormalities relate to amyloid deposition, a marker of Alzheimer pathology, remains unclear. This cross-sectional study examined the association of white matter abnormalities with cortical amyloid in a community sample of older adults without dementia and examined the moderating effect of race. Methods and Results Participants from the ARIC-PET (Atherosclerosis Risk in Communities-Positron Emission Tomography) study underwent brain magnetic resonance imaging, which quantified white matter hyperintensity volume and microstructural integrity using diffusion …

Air Pollution Particulate Matter Exposure And Chronic Cerebral Hypoperfusion And Measures Of White Matter Injury In A Murine Model, Qinghai Liu, Michelle Connor, Et Al

Open Access Publications

BACKGROUND: Exposure to ambient air pollution particulate matter (PM) is associated with increased risk of dementia and accelerated cognitive loss. Vascular contributions to cognitive impairment are well recognized. Chronic cerebral hypoperfusion (CCH) promotes neuroinflammation and blood-brain barrier weakening, which may augment neurotoxic effects of PM.

OBJECTIVES: This study examined interactions of nanoscale particulate matter (nPM; fine particulate matter with aerodynamic diameter

METHODS: nPM was collected using a particle sampler near a Los Angeles, California, freeway. Mice were exposed to 10 wk of reaerosolized nPM or filtered air (FA) for 150 h. CCH was induced by BCAS surgery. Mice (C57BL/6J males) …

Predicting The Environmental Suitability For Onchocerciasis In Africa As An Aid To Elimination Planning, Elizabeth A. Cromwell, Ziyad Al-Aly, Et Al

Open Access Publications

Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where …

Genome-Wide Association Study Of Circulating Interleukin 6 Levels Identifies Novel Loci, Tarunveer S. Ahluwalia, Mary F. Feitosa, Et Al.

2020-Current year OA Pubs

No abstract provided.

Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology And Demyelination Caused By Hypoperfusion, Mikko T Huuskonen, Qinghai Liu, Krista Lamorie-Foote, Kristina Shkirkova, Michelle Connor, Arati Patel, Axel Montagne, Hans Baertsch, Constantinos Sioutas, Todd E Morgan, Caleb E Finch, Berislav V Zlokovic, William J Mack

Open Access Publications

Cerebrovascular pathologies are commonly associated with dementia. Because air pollution increases arterial disease in humans and rodent models, we hypothesized that air pollution would also contribute to brain vascular dysfunction. We examined the effects of exposing mice to nanoparticulate matter (nPM; aerodynamic diameter ≤200 nm) from urban traffic and interactions with cerebral hypoperfusion. C57BL/6 mice were exposed to filtered air or nPM with and without bilateral carotid artery stenosis (BCAS) and analyzed by multiparametric MRI and histochemistry. Exposure to nPM alone did not alter regional cerebral blood flow (CBF) or blood brain barrier (BBB) integrity. However, nPM worsened the white …

Apathy, Cognitive Impairment, And Social Support Contribute To Participation In Cognitively Demanding Activities Poststroke, Amy Ho, Marjorie L. Nicholas, Chaitali Dagli, Lisa Tabor Connor

Open Access Publications

No abstract provided.