Digital Commons Network^™

Outcomes From An Interprofessional, Dementia-Focused, Telementoring Program: A Brief Report, Julianna Fernandez, Kathryn S Agarwal, Amber B Amspoker, Kyler M Godwin, Erial Green, Sabrina Pickens, Jasmin Lindo, Ali Abbas Asghar-Ali

Faculty, Staff and Students Publications

Despite a burgeoning older-adult population, the number of healthcare professionals with geriatric expertise continues to lag behind. In 2014, the American Geriatrics Society’s position statement encouraged interprofessional training for healthcare professionals. Telementoring remotely connects clinicians with specialists for education and group mentoring. This dementia-focused, 11-month, 1-hour each, telementoring program was modeled on the Alzheimer’s Association ECHO. Our interprofessional expert panel consisted of a geriatrician, a geriatric psychiatrist, an adult nurse practitioner (with geriatrics expertise), 2 geriatric pharmacists, a licensed social worker (coordinating a dementia day program), and a project coordinator. Learners were residents in family medicine and general psychiatry, physician …

Anemia, Iron Deficiency, And Cause-Specific Mortality: The Atherosclerosis Risk In Communities Study, Ethan J Cannon, Jeffrey R Misialek, Leo F Buckley, Iman A F Aboelsaad, Christie M Ballantyne, John Leister, James S Pankow, Pamela L Lutsey

Faculty, Staff and Students Publications

Introduction: Anemia is a risk factor for all-cause mortality in older adults. Iron deficiency may also be associated with adverse outcomes, independent of its role in causing anemia. This study tested the hypotheses that anemia, and low ferritin among non-anemic participants, were associated with all-cause and cause-specific mortality in a community-based cohort of older adults.

Methods: Fasting blood was obtained from 5,070 ARIC participants (median age: 75 years) in 2011-2013. Anemia was defined by hemoglobin concentrations < 12 g/dL in women and < 13 g/dL in men. We classified 4,020 non-anemic participants by quartiles of plasma ferritin, measured by the SomaScan proteomics platform. Cox proportional hazards regression was used. Mortality was ascertained via phone calls with proxies as part of twice-yearly cohort follow-up, surveillance of local hospital discharge indexes, state death records, and linkage to the National Death Index.

Results: Of the total participants, 21% had anemia at baseline. Over a median of 7.5 years, there were 1,147 deaths, including 357 due to …

Parkinson's Disease And Other Alzheimer's Disease And Related Dementia Pathologies And The Progression Of Parkinsonism In Older Adults, Aron S Buchman, Lei Yu, Shahram Oveisgharan, Andrea R Zammit, Tianhao Wang, Joshua M Shulman, Veronique Vanderhorst, Sukrit Nag, David A Bennett

Faculty, Staff and Students Publications

BACKGROUND: The interrelationship of parkinsonism, Parkinson's disease (PD) and other Alzheimer's disease (AD) and Alzheimer's disease and related dementias (ADRD) pathologies is unclear.

OBJECTIVE: We examined the progression of parkinsonian signs in adults with and without parkinsonism, and their underlying brain pathologies.

METHODS: Annual parkinsonian signs were based on a modified Unified Parkinson's Disease Rating Scale. We used linear mixed effects models to compare the progression of parkinsonian signs in 3 groups categorized based on all available clinical evaluations: Group1 (never parkinsonism or clinical PD), Group2 (ever parkinsonism, but never clinical PD), Group3 (ever clinical PD). In decedents, we examined …

Wildland Fires Worsened Population Exposure To Pm25 Pollution In The Contiguous United States, Danlu Zhang, Wenhao Wang, Yuzhi Xi, Jianzhao Bi, Yun Hang, Qingyang Zhu, Qiang Pu, Howard Chang, Yang Liu

Faculty, Staff and Student Publications

As wildland fires become more frequent and intense, fire smoke has significantly worsened the ambient air quality, posing greater health risks. to better understand the impact of wildfire smoke on air quality, we developed a modeling system to estimate daily PM

Aging And Urinary Control: Alterations In The Brain-Bladder Axis., Cara C Hardy, Ron Korstanje

Faculty Research 2023

Age-associated alterations in bladder control affect millions of older adults, with a heavy burden added to families both economically and in quality of life. Therapeutic options are limited with poor efficacy in older adults, lending to a growing need to address the gaps in our current understanding of urinary tract aging. This review summarizes the current knowledge of age-associated alterations in the structure and function of the brain-bladder axis and identifies important gaps in the field that have yet to be addressed. Urinary aging is associated with decreased tissue responsiveness, decreased control over the voiding reflex, signaling dysfunction along the …

Prostate Safety Events During Testosterone Replacement Therapy In Men With Hypogonadism: A Randomized Clinical Trial, Shalender Bhasin, Thomas G Travison, Karol M Pencina, Michael O'Leary, Glenn R Cunningham, A Michael Lincoff, Steven E Nissen, M Scott Lucia, Mark A Preston, Mohit Khera, Nader Khan, Michael C Snabes, Xue Li, Catherine M Tangen, Kevin A Buhr, Ian M Thompson

Faculty, Staff and Students Publications

IMPORTANCE: The effect of testosterone replacement therapy (TRT) on the risk of prostate cancer and other adverse prostate events is unknown.

OBJECTIVE: To compare the effect of TRT vs placebo on the incidences of high-grade prostate cancers (Gleason score ≥4 + 3), any prostate cancer, acute urinary retention, invasive prostate procedures, and pharmacologic treatment for lower urinary tract symptoms in men with hypogonadism.

DESIGN, SETTING, AND PARTICIPANTS: This placebo-controlled, double-blind randomized clinical trial enrolled 5246 men (aged 45-80 years) from 316 US trial sites who had 2 testosterone concentrations less than 300 ng/dL, hypogonadal symptoms, and cardiovascular disease (CVD) or …

Greater Socioenvironmental Risk Factors And Higher Chronic Pain Stage Are Associated With Thinner Bilateral Temporal Lobes, Lisa H Antoine, Burel R Goodin, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Previous research indicates ethnic/race group differences in pain and neurodegenerative diseases. Accounting for socioenvironmental factors reduces ethnic/race group differences in clinical and experimental pain. In the current study sample, we previously reported that in individuals with knee pain, ethnic/race group differences were observed in bilateral temporal lobe thickness, areas of the brain associated with risk for Alzheimer's disease, and related dementias. The purpose of the study was to determine if socioenvironmental factors reduce or account for previously observed ethnic/race group differences and explore if a combined effect of socioenvironmental risk and chronic pain severity on temporal lobe cortices is …

Relationships Among Development, Growth, Body Size, Reproduction, Aging, And Longevity - Trade-Offs And Pace-Of-Life., Rong Yuan, Erin Hascup, Kevin Hascup, Andrzej Bartke

Articles

Relationships of growth, metabolism, reproduction, and body size to the biological process of aging and longevity have been studied for decades and various unifying "theories of aging" have been proposed to account for the observed associations. In general, fast development, early sexual maturation leading to early reproductive effort, as well as production of many offspring, have been linked to shorter lifespans. The relationship of adult body size to longevity includes a remarkable contrast between the positive correlation in comparisons between different species and the negative correlation seen in comparisons of individuals within the same species. We now propose that longevity …

Association Between Microbiome And The Development Of Adverse Posttraumatic Neuropsychiatric Sequelae After Traumatic Stress Exposure, Abigail L Zeamer, Stacey L House, Et Al.

2020-Current year OA Pubs

Patients exposed to trauma often experience high rates of adverse post-traumatic neuropsychiatric sequelae (APNS). The biological mechanisms promoting APNS are currently unknown, but the microbiota-gut-brain axis offers an avenue to understanding mechanisms as well as possibilities for intervention. Microbiome composition after trauma exposure has been poorly examined regarding neuropsychiatric outcomes. We aimed to determine whether the gut microbiomes of trauma-exposed emergency department patients who develop APNS have dysfunctional gut microbiome profiles and discover potential associated mechanisms. We performed metagenomic analysis on stool samples (n = 51) from a subset of adults enrolled in the Advancing Understanding of RecOvery afteR traumA …

Relationship Of Race With Functional And Clinical Outcomes With The Rehab-Hf Multidomain Physical Rehabilitation Intervention For Older Patients With Acute Heart Failure, Olivia N. Gilbert, Robert J. Mentz, Alain G. Bertoni, Dalane W. Kitzman, David J. Whellan, Gordon R. Reeves, Pamela W. Duncan, Michael Benjamin Nelson, Vanessa Blumer, Haiying Chen, Shelby D. Reed, Bharathi Upadhya, Christopher M. O'Connor, Amy M. Pastva

Department of Medicine Faculty Papers

Background

The REHAB‐HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) randomized trial demonstrated that a 3‐month transitional, tailored, progressive, multidomain physical rehabilitation intervention improves physical function, frailty, depression, and health‐related quality of life among older adults with acute decompensated heart failure. Whether there is differential intervention efficacy by race is unknown.

Methods and Results

In this prespecified analysis, differential intervention effects by race were explored at 3 months for physical function (Short Physical Performance Battery [primary outcome], 6‐Minute Walk Distance), cognition, depression, frailty, health‐related quality of life (Kansas City Cardiomyopathy Questionnaire, EuroQoL 5‐Dimension‐5‐Level Questionnaire) and at 6 months for …

Multimodal Analysis Of Secondary Cerebellar Alterations After Pediatric Traumatic Brain Injury, Finian Keleher, Hannah M Lindsey, Rebecca Kerestes, Houshang Amiri, Robert F Asarnow, Talin Babikian, Brenda Bartnik-Olson, Erin D Bigler, Karen Caeyenberghs, Carrie Esopenko, Linda Ewing-Cobbs, Christopher C Giza, Naomi J Goodrich-Hunsaker, Cooper B Hodges, Kristen R Hoskinson, Andrei Irimia, Marsh Königs, Jeffrey E Max, Mary R Newsome, Alexander Olsen, Nicholas P Ryan, Adam T Schmidt, Dan J Stein, Stacy J Suskauer, Ashley L Ware, Anne L Wheeler, Brandon A Zielinski, Paul M Thompson, Ian H Harding, David F Tate, Elisabeth A Wilde, Emily L Dennis

Faculty, Staff and Student Publications

Importance: Traumatic brain injury (TBI) is known to cause widespread neural disruption in the cerebrum. However, less is known about the association of TBI with cerebellar structure and how such changes may alter executive functioning.

Objective: To investigate alterations in subregional cerebellum volume and cerebral white matter microstructure after pediatric TBI and examine subsequent changes in executive function.

Design, setting, and participants: This retrospective cohort study combined 12 data sets (collected between 2006 and 2020) from 9 sites in the Enhancing Neuroimaging Genetics Through Meta-Analysis Consortium Pediatric TBI working group in a mega-analysis of cerebellar structure. Participants with TBI or …

Depression By Gender And Associated Factors Among Older Adults In India: Implications For Age-Friendly Policies, Ronak Paul, T. Muhammad, Rashmi Rashmi, Palak Sharma, Shobhit Srivastava, Preeti Zanwar

College of Population Health Faculty Papers

Inspite of implementing policies to control mental health problems, depression remains a severe health concern among older adults in India. We examined self-reported differences in the depression among older men and women in India and examined associated factors for gender differences in depression at the population level. We utilized nationally representative data from the Longitudinal Aging Study in India (LASI) wave I, for years 2017-2019. Our analytical sample comprised of 30,637 older adults ages 60 years and above (14,682 men and 15,655 women). We conducted descriptive statistics and Chi-Square tests followed by binary logistic regression and multivariate decomposition analyses to …

Association Between Whole Blood-Derived Mitochondrial Dna Copy Number, Low-Density Lipoprotein Cholesterol, And Cardiovascular Disease Risk, Xue Liu, Xianbang Sun, Yuankai Zhang, Wenqing Jiang, Meng Lai, Kerri L Wiggins, Laura M Raffield, Lawrence F Bielak, Wei Zhao, Achilleas Pitsillides, Jeffrey Haessler, Yinan Zheng, Thomas W Blackwell, Jie Yao, Xiuqing Guo, Yong Qian, Bharat Thyagarajan, Nathan Pankratz, Stephen S Rich, Kent D Taylor, Patricia A Peyser, Susan R Heckbert, Sudha Seshadri, Eric Boerwinkle, Megan L Grove, Nicholas B Larson, Jennifer A Smith, Ramachandran S Vasan, Annette L Fitzpatrick, Myriam Fornage, Jun Ding, April P Carson, Goncalo Abecasis, Josée Dupuis, Alexander Reiner, Charles Kooperberg, Lifang Hou, Bruce M Psaty, James G Wilson, Daniel Levy, Jerome I Rotter, Joshua C Bis, Claudia L Satizabal, Dan E Arking, Chunyu Liu

Faculty, Staff and Student Publications

Background The relationship between mitochondrial DNA copy number (mtDNA CN) and cardiovascular disease remains elusive. Methods and Results We performed cross-sectional and prospective association analyses of blood-derived mtDNA CN and cardiovascular disease outcomes in 27 316 participants in 8 cohorts of multiple racial and ethnic groups with whole-genome sequencing. We also performed Mendelian randomization to explore causal relationships of mtDNA CN with coronary heart disease (CHD) and cardiometabolic risk factors (obesity, diabetes, hypertension, and hyperlipidemia).

Tuberculosis Presentation And Outcomes In Older Hispanic Adults From Tamaulipas, Mexico, Belinda A Medrano, Miryoung Lee, Gretchen Gemeinhardt, Javier E Rodríguez-Herrera, Moncerrato García-Viveros, Blanca I Restrepo

Faculty, Staff and Student Publications

Older people are at high risk of developing and dying from pulmonary infections like tuberculosis (TB), but there are few studies among them, particularly in Hispanics. To address these gaps, we sought to identify host factors associated with TB and adverse treatment outcomes in older Hispanics by conducting a cross-sectional study of TB surveillance data from Tamaulipas, Mexico (2006-2013; n = 8381). Multivariable logistic regressions were assessed for older adults (OA ≥65 years) when compared to young (YA, 18-39 years) and middle-aged adults (40-64 years). We found that the OA had features associated with a less complicated TB (e.g., lower …

Social Determinants Of Health And Disparate Disability Accumulation In A Cohort Of Black, Hispanic, And White Patients With Multiple Sclerosis, Michael C Robertson, Brian Downer, Paul E Schulz, Rafael Samper-Ternent, Elizabeth J Lyons, Sadaf Arefi Milani

Faculty, Staff and Student Publications

OBJECTIVES: Mexico has a rapidly aging population at risk for cognitive impairment. Social and leisure activities may protect against cognitive decline in older adults. The benefits of these behaviors may vary by patterns of cognitive impairment. The objectives of this study were to identify latent states of cognitive functioning, model the incidence of transitions between these states, and investigate how social and leisure activities were associated with state transitions over a 6-year period in Mexican adults aged 60 and older.

METHODS: We performed latent transition analyses to identify distinct cognitive statuses in the 2012 and 2018 waves of the Mexican …

Availability Of Family Caregiver Programs In Us Cancer Centers, J Nicholas Odom, Allison Applebaum, Marie A Bakitas, Tara Bryant, Erin Currie, Kayleigh Curry, Heidi Donovan, Maria E Fernandez, Betty Ferrell, Andres Azuero, Tamryn F Gray, Bailey A Hendricks, Diane Meier, Chandylen Nightingale, Susan Reinhard, Timothy S Sannes, Katherine Sterba, Heather M Young

Faculty, Staff and Student Publications

Importance: Family caregivers provide the majority of health care to the 18 million patients with cancer in the US. Yet despite providing complex medical and nursing care, a large proportion of caregivers report no formal support or training. In recognition of this gap, many interventions to support cancer caregivers have been developed and tested over the past 2 decades. However, there are few system-level data on whether US cancer centers have adopted and implemented these interventions.

Objective: To describe and characterize the availability of family caregiver support programs in US cancer centers.

Design, setting, and participants: This cross-sectional national survey …

Longitudinal Associations Between Cognitive Functioning And Depressive Symptoms Among Couples In The Mexican Health And Aging Study, Joan K Monin, Gail Mcavay, Katie Newkirk, Rafael Samper-Ternent

Faculty, Staff and Student Publications

OBJECTIVE: To examine the bidirectional associations between older adult spouses' cognitive functioning and depressive symptoms over time and replicate previous findings from the United States (US) in Mexico.

DESIGN: Longitudinal, dyadic path analysis with the actor-partner interdependence model.

SETTING: Data were from the three most recent interview waves (2012, 2015, and 2018) of the Mexican Health and Aging Study (MHAS), a longitudinal national study of adults aged 50+ years in Mexico.

PARTICIPANTS: Husbands and wives from 905 community-dwelling married couples (N = 1,810).

MEASUREMENTS: The MHAS cognitive battery measured cognitive function. Depressive symptoms were assessed using a modified nine-item Center …

Racial/Ethnic Group Differences In Older Adults' Involvement With Adult Protective Services, Kenneth J Steinman, Jason Burnett, Rebecca Hoffman

Faculty, Staff and Student Publications

This paper represents the first study to focus on quantifying racial/ethnic group differences in older adults' involvement with adult protective services (APS).  Across 3 independent county programs, the rate of APS reports was about twice as high for Black older adults compared to White older adults.  These differences were greater for clients who were older and male but remained similar across allegation type.  The percent of reports validated was slightly but consistently lower for Black clients than for White clients, and a lower percentage of Black clients' cases were closed due to investigation or service refusal. Findings for Hispanic clients …

The Pre-Adaptation Of A Stroke-Specific Self-Management Program Among Older Adults, Timothy Reistetter, Kimberly Hreha, Julianna M Dean, Monique R Pappadis, Rachel R Deer, Chih-Ying Li, Ickpyo Hong, Annalisa Na, Sara Nowakowski, Hashem M Shaltoni, Suresh K Bhavnani

Faculty, Staff and Students Publications

Objectives:

Managing multimorbidity as aging stroke patients is complex; standard self-management programs necessitate adaptations. We used visual analytics to examine complex relationships among aging stroke survivors’ comorbidities. These findings informed pre-adaptation of a component of the Chronic Disease Self-Management Program.

Methods:

Secondary analysis of 2013–2014 Medicare claims with stroke as an index condition, hospital readmission within 90 days (n=42,938), and 72 comorbidities. Visual analytics identified patient subgroups and co-occurring comorbidities. Guided by the framework for reporting adaptations and modifications to evidence-based interventions (FRAME), an interdisciplinary team developed vignettes that highlighted multimorbidity to customize the self-management program.

Results:

There were five …

Association Between Alcohol Consumption And Ectopic Fat In The Multi-Ethnic Study Of Atherosclerosis, Richard Kazibwe, Parag A Chevli, Joni K Evans, Matthew Allison, Erin D Michos, Alexis C Wood, Jingzhong Ding, Michael D Shapiro, Morgana Mongraw-Chaffin

Faculty, Staff and Students Publications

Background The relationship between alcohol consumption and ectopic fat distribution, both known factors for cardiovascular disease, remains understudied. Therefore, we aimed to examine the association between alcohol consumption and ectopic adiposity in adults at risk for cardiovascular disease. Methods and Results In this cross-sectional analysis, we categorized alcohol intake among participants in MESA (Multi-Ethnic Study of Atherosclerosis) as follows (drinks/day): <1 >(light drinking), 1 to 2 (moderate drinking), >2 (heavy drinking), former drinking, and lifetime abstention. Binge drinking was defined as consuming ≥5 drinks on 1 occasion in the past month. Visceral, subcutaneous, and intermuscular fat area, pericardial fat volume, and …

Evaluation Of The Electronic Clinical Dementia Rating For Dementia Screening, Rachel L Nosheny, Daniel Yen, Krista Moulder, Connie Mayo, Maureen Mcmillan, John C Morris, Yan Li, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The Clinical Dementia Rating (CDR) is a well-validated instrument widely used to detect and stage dementia due to Alzheimer disease. The digital Electronic Clinical Dementia Rating (eCDR) can be remotely self-administered and automatically scored, with potential to facilitate efficient dementia screening and staging.

OBJECTIVE: To evaluate the association of the eCDR with the CDR and other in-clinic assessments for screening older adults for cognitive impairment.

DESIGN, SETTING, AND PARTICIPANTS: This multisite, cross-sectional study used baseline data from a longitudinal, observational study from 2020 to 2023, including up to 3 years of follow-up. Participants were enrolled from 3 Alzheimer Disease …

Multiancestry Analysis Of The Hla Locus In Alzheimer’S And Parkinson’S Diseases Uncovers A Shared Adaptive Immune Response Mediated By Hla-Drb1*04 Subtypes, Yann Le Guen, Guo Luo, Aditya Ambati, Vincent Damotte, Iris Jansen, Eric Yu, Aude Nicolas, Itziar De Rojas, Thiago Peixoto Leal, Akinori Miyashita, Céline Bellenguez, Michelle Mulan Lian, Kayenat Parveen, Takashi Morizono, Hyeonseul Park, Benjamin Grenier-Boley, Tatsuhiko Naito, Fahri Küçükali, Seth D Talyansky, Selina Maria Yogeshwar, Vicente Sempere, Wataru Satake, Victoria Alvarez, Beatrice Arosio, Michael E Belloy, Luisa Benussi, Anne Boland, Barbara Borroni, María J Bullido, Paolo Caffarra, Jordi Clarimon, Antonio Daniele, Daniel Darling, Stéphanie Debette, Jean-François Deleuze, Martin Dichgans, Carole Dufouil, Emmanuel During, Emrah Düzel, Daniela Galimberti, Guillermo Garcia-Ribas, José María García-Alberca, Pablo García-González, Vilmantas Giedraitis, Oliver Goldhardt, Caroline Graff, Edna Grünblatt, Olivier Hanon, Lucrezia Hausner, Stefanie Heilmann-Heimbach, Henne Holstege, Jakub Hort, Yoo Jin Jung, Deckert Jürgen, Silke Kern, Teemu Kuulasmaa, Kun Ho Lee, Ling Lin, Carlo Masullo, Patrizia Mecocci, Shima Mehrabian, Alexandre De Mendonça, Mercè Boada, Pablo Mir, Susanne Moebus, Fermin Moreno, Benedetta Nacmias, Gael Nicolas, Shumpei Niida, Børge G Nordestgaard, Goran Papenberg, Janne Papma, Lucilla Parnetti, Florence Pasquier, Pau Pastor, Oliver Peters, Yolande A L Pijnenburg, Gerard Piñol-Ripoll, Julius Popp, Laura Molina Porcel, Raquel Puerta, Jordi Pérez-Tur, Innocenzo Rainero, Inez Ramakers, Luis M Real, Steffi Riedel-Heller, Eloy Rodriguez-Rodriguez, Owen A Ross, Luis Jose Royo, Dan Rujescu, Nikolaos Scarmeas, Philip Scheltens, Norbert Scherbaum, Anja Schneider, Davide Seripa, Ingmar Skoog, Vincenzo Solfrizzi, Gianfranco Spalletta, Alessio Squassina, John Van Swieten, Raquel Sánchez-Valle, Eng-King Tan, Thomas Tegos, Charlotte Teunissen, Jesper Qvist Thomassen, Lucio Tremolizzo, Martin Vyhnalek, Frans Verhey, Margda Waern, Jens Wiltfang, Jing Zhang, Eadb, Gr@Ace Study Group, Degesco Consortium, Demgene, Eadi, Gerad, Asian Parkinson’S Disease Genetics Consortium, Henrik Zetterberg, Kaj Blennow, Zihuai He, Julie Williams, Philippe Amouyel, Frank Jessen, Patrick G Kehoe, Ole A Andreassen, Cornelia Van Duin, Magda Tsolaki, Pascual Sánchez-Juan, Ruth Frikke-Schmidt, Kristel Sleegers, Tatsushi Toda, Anna Zettergren, Martin Ingelsson, Yukinori Okada, Giacomina Rossi, Mikko Hiltunen, Jungsoo Gim, Kouichi Ozaki, Rebecca Sims, Jia Nee Foo, Wiesje Van Der Flier, Takeshi Ikeuchi, Alfredo Ramirez, Ignacio Mata, Agustín Ruiz, Ziv Gan-Or, Jean-Charles Lambert, Michael D Greicius, Emmanuel Mignot

Faculty, Staff and Students Publications

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. …

An Update On The Healthy Soldier Effect In U.S. Veterans, Erin Sullivan-Baca, Rizwana Rehman, Zulfi Haneef

Faculty, Staff and Students Publications

Introduction: The healthy soldier effect (HSE) describes a phenomenon of enduring health and lower mortality among veterans due in part to initial screening procedures and health care access. Although early data were supportive of a broad HSE among former military members, more recent investigations have suggested a possible attenuation of the effect with older age. The present study aimed to provide an update of the HSE using an expansive Veterans Health Administration (VHA)-wide sample with a particular focus on age and sex effects.

Materials and methods: Mortality data for veterans within the VHA were obtained from the VHA Support Service …

Enigma Chek2gether Project: A Comprehensive Study Identifies Functionally Impaired Chek2 Germline Missense Variants Associated With Increased Breast Cancer Risk, Lenka Stolarova, Petra Kleiblova, Petra Zemankova, Barbora Stastna, Marketa Janatova, Jana Soukupova, Maria Isabel Achatz, Christine Ambrosone, Paraskevi Apostolou, Banu K Arun, Paul Auer, Mollie Barnard, Birgitte Bertelsen, Biobank Japan, Marinus J Blok, Nicholas Boddicker, Joan Brunet, Elizabeth S Burnside, Mariarosaria Calvello, Ian Campbell, Sock Hoai Chan, Fei Chen, Jian Bang Chiang, Anna Coppa, Laura Cortesi, Ana Crujeiras-González, Consortium Czecanca, Kim De Leeneer, Robin De Putter, Allison Depersia, Lisa Devereux, Susan Domchek, Anna Efremidis, Christoph Engel, Corinna Ernst, D Gareth R Evans, Lidia Feliubadaló, Florentia Fostira, Olivia Fuentes-Ríos, Encarna B Gómez-García, Sara González, Christopher Haiman, Thomas Van Overeem Hansen, Jan Hauke, James Hodge, Chunling Hu, Hongyan Huang, Nur Diana Binte Ishak, Yusuke Iwasaki, Irene Konstantopoulou, Peter Kraft, James Lacey, Conxi Lázaro, Na Li, Weng Khong Lim, Sara Lindstrom, Adriana Lori, Elana Martinez, Alexandra Martins, Koichi Matsuda, Giuseppe Matullo, Simone Mcinerny, Kyriaki Michailidou, Marco Montagna, Alvaro N A Monteiro, Luigi Mori, Katherine Nathanson, Susan L Neuhausen, Heli Nevanlinna, Janet E Olson, Julie Palmer, Barbara Pasini, Alpa Patel, Maria Piane, Bruce Poppe, Paolo Radice, Alessandra Renieri, Nicoletta Resta, Marcy E Richardson, Toon Rosseel, Kathryn J Ruddy, Marta Santamariña, Elizabeth Santana Dos Santos, Lauren Teras, Amanda E Toland, Amy Trentham-Dietz, Celine M Vachon, Alexander E Volk, Nana Weber-Lassalle, Jeffrey N Weitzel, Lisa Wiesmuller, Stacey Winham, Siddhartha Yadav, Drakoulis Yannoukakos, Song Yao, Valentina Zampiga, Magnus Zethoven, Ze Wen Zhang, Tomas Zima, Amanda B Spurdle, Ana Vega, Maria Rossing, Jesús Del Valle, Arcangela De Nicolo, Eric Hahnen, Kathleen B M Claes, Joanne Ngeow, Yukihide Momozawa, Paul A James, Fergus J Couch, Libor Macurek, Zdenek Kleibl

Faculty, Staff and Student Publications

PURPOSE: Germline pathogenic variants in CHEK2 confer moderately elevated breast cancer risk (odds ratio, OR ∼ 2.5), qualifying carriers for enhanced breast cancer screening. Besides pathogenic variants, dozens of missense CHEK2 variants of uncertain significance (VUS) have been identified, hampering the clinical utility of germline genetic testing (GGT).

EXPERIMENTAL DESIGN: We collected 460 CHEK2 missense VUS identified by the ENIGMA consortium in 15 countries. Their functional characterization was performed using CHEK2-complementation assays quantifying KAP1 phosphorylation and CHK2 autophosphorylation in human RPE1-CHEK2-knockout cells. Concordant results in both functional assays were used to categorize CHEK2 VUS from 12 ENIGMA case-control datasets, including …

Development And Validation Of An Automated Image-Based Deep Learning Platform For Sarcopenia Assessment In Head And Neck Cancer, Zezhong Ye, Anurag Saraf, Yashwanth Ravipati, Frank Hoebers, Paul J Catalano, Yining Zha, Anna Zapaishchykova, Jirapat Likitlersuang, Christian Guthier, Roy B Tishler, Jonathan D Schoenfeld, Danielle N Margalit, Robert I Haddad, Raymond H Mak, Mohamed Naser, Kareem A Wahid, Jaakko Sahlsten, Joel Jaskari, Kimmo Kaski, Antti A Mäkitie, Clifton D Fuller, Hugo J W L Aerts, Benjamin H Kann

Faculty, Staff and Student Publications

Importance: Sarcopenia is an established prognostic factor in patients with head and neck squamous cell carcinoma (HNSCC); the quantification of sarcopenia assessed by imaging is typically achieved through the skeletal muscle index (SMI), which can be derived from cervical skeletal muscle segmentation and cross-sectional area. However, manual muscle segmentation is labor intensive, prone to interobserver variability, and impractical for large-scale clinical use.

Objective: To develop and externally validate a fully automated image-based deep learning platform for cervical vertebral muscle segmentation and SMI calculation and evaluate associations with survival and treatment toxicity outcomes.

Design, setting, and participants: For this prognostic study, …

Cerebrospinal Fluid Proteomics Define The Natural History Of Autosomal Dominant Alzheimer's Disease, Erik C B Johnson, Brian A Gordon, Eric Mcdade, Nicolas R Barthélemy, Celeste M Karch, Chengjie Xiong, Carlos Cruchaga, Richard J Perrin, John C Morris, Tammie L S Benzinger, Randall J Bateman, Anne M Fagan, Et Al.

2020-Current year OA Pubs

Alzheimer's disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes-aggregation of the amyloid-β (Aβ) peptide into plaques and the microtubule protein tau into neurofibrillary tangles (NFTs)-are hallmarks of the disease. However, other pathological brain processes are thought to be key disease mediators of Aβ plaque and NFT pathology. How these additional pathologies evolve over the course of the disease is currently unknown. Here we show that proteomic measurements in autosomal dominant AD cerebrospinal fluid (CSF) linked to brain protein coexpression can be used to characterize the evolution of AD pathology over a timescale spanning …

When A Calorie Is Not Just A Calorie: Diet Quality And Timing As Mediators Of Metabolism And Healthy Aging, Maria M Mihaylova, Amandine Chaix, Mirela Delibegovic, Jon J Ramsey, Joseph Bass, Girish Melkani, Rajat Singh, Zheng Chen, William W Ja, Michele Shirasu-Hiza, Mary N Latimer, Julie A Mattison, Anna E Thalacker-Mercer, Vishwa Deep Dixit, Satchidananda Panda, Dudley W Lamming

Faculty, Staff and Student Publications

An epidemic of obesity has affected large portions of the world, increasing the risk of developing many different age-associated diseases, including cancer, cardiovascular disease, and diabetes. In contrast with the prevailing notion that "a calorie is just a calorie," there are clear differences, within and between individuals, in the metabolic response to different macronutrient sources. Recent findings challenge this oversimplification; calories from different macronutrient sources or consumed at different times of day have metabolic effects beyond their value as fuel. Here, we summarize discussions conducted at a recent NIH workshop that brought together experts in calorie restriction, macronutrient composition, and …

Evaluating Approaches For Constructing Polygenic Risk Scores For Prostate Cancer In Men Of African And European Ancestry, Burcu F Darst, Jiayi Shen, Ravi K Madduri, Alexis A Rodriguez, Yukai Xiao, Xin Sheng, Edward J Saunders, Tokhir Dadaev, Mark N Brook, Thomas J Hoffmann, Kenneth Muir, Peggy Wan, Loic Le Marchand, Lynne Wilkens, Ying Wang, Johanna Schleutker, Robert J Macinnis, Cezary Cybulski, David E Neal, Børge G Nordestgaard, Sune F Nielsen, Jyotsna Batra, Judith A Clements, Australian Prostate Cancer Bioresource, Henrik Grönberg, Nora Pashayan, Ruth C Travis, Jong Y Park, Demetrius Albanes, Stephanie Weinstein, Lorelei A Mucci, David J Hunter, Kathryn L Penney, Catherine M Tangen, Robert J Hamilton, Marie-Élise Parent, Janet L Stanford, Stella Koutros, Alicja Wolk, Karina D Sørensen, William J Blot, Edward D Yeboah, James E Mensah, Yong-Jie Lu, Daniel J Schaid, Stephen N Thibodeau, Catharine M West, Christiane Maier, Adam S Kibel, Géraldine Cancel-Tassin, Florence Menegaux, Esther M John, Eli Marie Grindedal, Kay-Tee Khaw, Sue A Ingles, Ana Vega, Barry S Rosenstein, Manuel R Teixeira, Nc-La Pcap Investigators, Manolis Kogevinas, Lisa Cannon-Albright, Chad Huff, Luc Multigner, Radka Kaneva, Robin J Leach, Hermann Brenner, Ann W Hsing, Rick A Kittles, Adam B Murphy, Christopher J Logothetis, Susan L Neuhausen, William B Isaacs, Barbara Nemesure, Anselm J Hennis, John Carpten, Hardev Pandha, Kim De Ruyck, Jianfeng Xu, Azad Razack, Soo-Hwang Teo, Canary Pass Investigators, Lisa F Newcomb, Jay H Fowke, Christine Neslund-Dudas, Benjamin A Rybicki, Marija Gamulin, Nawaid Usmani, Frank Claessens, Manuela Gago-Dominguez, Jose Esteban Castelao, Paul A Townsend, Dana C Crawford, Gyorgy Petrovics, Graham Casey, Monique J Roobol, Jennifer F Hu, Sonja I Berndt, Stephen K Van Den Eeden, Douglas F Easton, Stephen J Chanock, Michael B Cook, Fredrik Wiklund, John S Witte, Rosalind A Eeles, Zsofia Kote-Jarai, Stephen Watya, John M Gaziano, Amy C Justice, David V Conti, Christopher A Haiman

Faculty, Staff and Student Publications

Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS269). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS269. Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California Uganda Study and 8,046 cases and …

Targeting Energy Intake And Circadian Biology To Engage Mechanisms Of Aging In Older Adults With Obesity: Calorie Restriction And Time-Restricted Eating, Satchidananda Panda, Geraldine Maier, Dennis T Villareal

Faculty, Staff and Students Publications

With the rise in obesity across age groups, it has been a hindrance to engaging in physical activity and mobility in older adults. Daily calorie restriction (CR) up to 25% has been the cornerstone of obesity management even though the safety in older adults remains incompletely understood. Although some adults can follow CR with clinically significant weight loss and improved health metrics, CR faces 2 obstacles-many fail to adopt CR and even among those who can adopt it short term, long-term compliance can be difficult. Furthermore, there is a continuing debate about the net benefits of CR-induced weight loss in …

Shared Care Networks Assisting Older Adults: New Insights From The National Health And Aging Trends Study, Mengyao Hu, Vicki A Freedman, Sarah E Patterson, Nora Lewis

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Caregiving research often assumes older adults receiving care have a primary caregiver who provides the bulk of care. Consequently, little is known about the extent to which care responsibilities are shared more evenly within a care network, the characteristics associated with sharing, or the consequences for meeting older adults' care needs.

RESEARCH DESIGN AND METHODS: We analyze a sample of U.S. older adults receiving care from the 2011 National Health and Aging Trends Study (n = 2,398). Based on variables reflecting differences in care hours, activities, and care provided by the whole network, we create network typologies …