Cognition and Perception Commons^™

Plasma Proteomic Characterization Of Motoric Cognitive Risk And Mild Cognitive Impairment, Gabriela T Gomez, Sanish Sathyan, Jingsha Chen, Myriam Fornage, Pascal Schlosser, Zhongsheng Peng, Jenifer Cordon, Priya Palta, Kevin J Sullivan, Adrienne Tin, B Gwen Windham, Rebecca F Gottesman, Nir Barzilai, Sofiya Milman, Joe Verghese, Josef Coresh, Keenan A Walker

Faculty, Staff and Student Publications

INTRODUCTION: Motoric cognitive risk (MCR) is a pre-dementia syndrome characterized by mobility and cognitive dysfunction. This study conducted a proteome-wide study of MCR and compared the proteomic signatures of MCR to that of mild cognitive impairment (MCI).

METHODS: Participants were classified as MCR using a memory questionnaire and 4-meter walk. We measured 4877 plasma proteins collected during late-life and midlife. Multivariable logistic regression related each protein to late-life MCR/MCI. MCR-associated proteins were replicated internally at midlife and in an external cohort.

RESULTS: Proteome-wide analysis (n = 4076) identified 25 MCR-associated proteins. Eight of these proteins remained associated with late-life MCR …

Associations Between Deficit Accumulation Frailty And Baseline Markers Of Lifestyle In The Us Pointer Trial, Mark A Espeland, Yitbarek N Demesie, Kayloni Olson, Samuel N Lockhart, Sarah E Tomaszewski Farias, Maryjo L Cleveland, Christy C Tangney, Lucia Crivelli, Heather M Snyder, Michele K York, Laura D Baker, Rachel A Whitmer, Rena R Wing, Katelyn R Garcia, Kathryn E Callahan

Faculty, Staff and Students Publications

BACKGROUND: Multidomain lifestyle interventions may have the potential to slow biological aging as captured by deficit accumulation frailty indices. We describe the distribution and composition of the 49-component frailty index developed by the U.S. POINTER clinical trial team of investigators and assess its cross-sectional associations with sociodemographic factors and markers chosen to be representative of behaviors targeted by the trial's multidomain interventions.

METHODS: We draw baseline data from the 2 111 volunteers enrolled in U.S. POINTER who were ages 60-79 years and at increased risk for cognitive decline. Frailty components were grouped into 9 domains. Associations that frailty index scores …

Biological Validation Of Peak-Width Of Skeletonized Mean Diffusivity As A Vcid Biomarker: The Markvcid Consortium, Alison M Luckey, Saptaparni Ghosh, Chen-Pin Wang, Alexa Beiser, Rebecca Bernal, Zhiguang Li, Djass Mbangdadji, Elyas Fadaee, Haykel Snoussi, Angel Gabriel Velarde Dediós, Hector A Trevino, Monica Goss, Laura J Hillmer, Christopher E Bauer, Adam M Staffaroni, Lara Stables, Marilyn Albert, Jayandra J Himali, Thomas H Mosley, Lars Forsberg, Vilmundur Guðnason, Baljeet Singh, Herpreet Singh, Kristin Schwab, Joel H Kramer, Gary A Rosenberg, Karl G Helmer, Steven M Greenberg, Mohamad Habes, Danny J J Wang, Brian T Gold, Hanzhang Lu, Arvind Caprihan, Myriam Fornage, Lenore J Launer, Konstantinos Arfanakis, Sudha Seshadri, Charles Decarli, Pauline Maillard, Claudia L Satizabal

Faculty, Staff and Student Publications

BACKGROUND: Peak-width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.

METHODS: We included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID-1) Consortium and three replication samples (Cohorts for Heart and Aging Research in Genomic Epidemiology = 6172, Rush University Medical Center = 287, University of California Davis Alzheimer's Disease Research Center = 567). PSMD was derived from diffusion tensor imaging using an automated algorithm. We related PSMD to a composite measure …

Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Wan-Ping Lee, Seung Hoan Choi, Margaret G Shea, Po-Liang Cheng, Beth A Dombroski, Achilleas N Pitsillides, Nancy L Heard-Costa, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Myriam Fornage, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project;, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso

Faculty, Staff and Student Publications

INTRODUCTION: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous.

METHODS: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data.

RESULTS: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10

DISCUSSION: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD.

HIGHLIGHTS: We determine the association of genetic variants with Alzheimer's disease (AD) using …

Initiation Of Hearing Aids Use And Incident Dementia Among Mid-To-Late Life Adults: The Health And Retirement Study 2010-2018, Jingkai Wei, Kun Li, Youngran Kim, Rahul Ghosal, Donglan Zhang, Anwar T Merchant, Casey Crump

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Hearing aids may reduce the risk of dementia among individuals with hearing loss. However, no evidence is available from randomized controlled trials (RCTs) on the effectiveness of hearing aids use in reducing incident dementia. Using target trial emulation, we leveraged an existing longitudinal cohort study to estimate the association between hearing aids initiation and risk of dementia.

RESEARCH DESIGN AND METHODS: The Health and Retirement Study was used to emulate target trials among non-institutionalized participants aged ≥50 years with self-reported hearing loss, without dementia at baseline, and without use of hearing aids in the previous 2 years. …

Clonal Hematopoiesis Of Indeterminate Potential Is Associated With Reduced Risk Of Cognitive Impairment In Patients With Chronic Kidney Disease, Cissy Xiao, Manjula Kurella Tamura, Yang Pan, Varun Rao, Celestin Missikpode, Caitlyn Vlasschaert, Tetsushi Nakao, Xiao Sun, Changwei Li, Zhijie Huang, Amanda Anderson, Md Mesbah Uddin, Do-Kyun Kim, Jonathan Taliercio, Rajat Deo, Zeenat Bhat, Dawei Xie, Panduranga Rao, Jing Chen, James P Lash, Jiang He, Pradeep Natarajan, James E Hixson, Kristine Yaffe, Tanika N Kelly, Cric Study Investigators

Faculty, Staff and Student Publications

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown.

Methods: We conducted time-to-event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing. Cognition was assessed using four validated tests in up to 6 years mean follow-up time. Incident cognitive impairment was defined as a test score one standard deviation below the baseline mean.

Results: Compared to non-carriers, CHIP carriers were markedly less likely to experience impairment in attention (adjusted …

Admixture Mapping Of Cognitive Function In Diverse Hispanic And Latino Adults: Results From The Hispanic Community Health Study/Study Of Latinos, Rui Xia, Xueqiu Jian, Amanda L Rodrigue, Jan Bressler, Eric Boerwinkle, Biqi Cui, Martha L Daviglus, Charles Decarli, Linda C Gallo, David C Glahn, Emma E M Knowles, Jee-Young Moon, Thomas H Mosley, Claudia L Satizabal, Tamar Sofer, Wassim Tarraf, Fernando Testai, John Blangero, Sudha Seshadri, Hector M González, Myriam Fornage

Faculty, Staff and Student Publications

INTRODUCTION: We conducted admixture mapping and fine-mapping analyses to identify ancestry-of-origin loci influencing cognitive abilities.

METHODS: We estimated the association of local ancestry intervals across the genome with five neurocognitive measures in 7140 diverse Hispanic and Latino adults (mean age 55 years). We prioritized genetic variants in associated loci and tested them for replication in four independent cohorts.

RESULTS: We identified nine local ancestry-associated regions for the five neurocognitive measures. There was strong biological support for the observed associations to cognitive function at all loci and there was statistical evidence of independent replication at 4q12, 9p22.1, and 13q12.13.

DISCUSSION: Our …

Prediction Of Disease-Free Survival For Precision Medicine Using Cooperative Learning On Multi-Omic Data, Georg Hahn, Dmitry Prokopenko, Julian Hecker, Sharon M Lutz, Kristina Mullin, Leinal Sejour, Winston Hide, Ioannis Vlachos, Stacia Desantis, Rudolph E Tanzi, Christoph Lange

Faculty, Staff and Student Publications

In precision medicine, both predicting the disease susceptibility of an individual and forecasting its disease-free survival are areas of key research. Besides the classical epidemiological predictor variables, data from multiple (omic) platforms are increasingly available. To integrate this wealth of information, we propose new methodology to combine both cooperative learning, a recent approach to leverage the predictive power of several datasets, and polygenic hazard score models. Polygenic hazard score models provide a practitioner with a more differentiated view of the predicted disease-free survival than the one given by merely a point estimate, for instance computed with a polygenic risk score. …

Risk Of Alzheimer's Disease And Related Dementias In Persons With Glaucoma: A National Cohort Study, Casey Crump, Jan Sundquist, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

PURPOSE: Glaucoma is a heterogeneous group of optic neuropathies that potentially may be associated with other cerebral neurodegenerative processes leading to dementia. However, prior studies have been inconsistent. We examined dementia risks after glaucoma diagnosis in a large population-based cohort.

DESIGN: National matched cohort study.

PARTICIPANTS: A total of 324 730 persons diagnosed with glaucoma during 1995-2017 in Sweden and 3 247 300 age- and sex-matched population-based controls without prior dementia.

METHODS: Cox regression was used to compute hazard ratios (HRs) for Alzheimer's disease (AD), vascular dementia (VaD), and all-cause dementia in persons with glaucoma compared with controls, adjusting for …

Association Of Plasma Ykl-40 With Mri, Csf, And Cognitive Markers Of Brain Health And Dementia, Matthew P Pase, Jayandra J Himali, Raquel Puerta, Alexa S Beiser, Mitzi M Gonzales, Claudia L Satizabal, Qiong Yang, Hugo J Aparicio, Daniel J Kojis, Charles S Decarli, Oscar L Lopez, Will Longstreth, Vilmundur Gudnason, Thomas H Mosley, Joshua C Bis, Alison Fohner, Bruce M Psaty, Mercè Boada, Pablo García-González, Sergi Valero, Marta Marquié, Russell Tracy, Lenore J Launer, Agustín Ruiz, Myriam Fornage, Sudha Seshadri

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored the utility of plasma YKL-40 as a biomarker for accelerated brain aging and dementia risk.

METHODS: We performed cross-sectional and prospective analyses of 4 community-based cohorts in the United States or Europe: the Age, Gene/Environment Susceptibility-Reykjavik Study, Atherosclerosis Risk in the Communities study, Coronary Artery Risk Development in Young Adults study, and Framingham Heart Study (FHS). YKL-40 was measured from stored plasma by a single laboratory using Mesoscale Discovery with levels log transformed and standardized within each cohort. Outcomes included MRI total …

The Ddhd2-Stxbp1 Interaction Mediates Long-Term Memory Via Generation Of Saturated Free Fatty Acids, Isaac O Akefe, Saber H Saber, Benjamin Matthews, Bharat G Venkatesh, Rachel S Gormal, Daniel G Blackmore, Suzy Alexander, Emma Sieriecki, Yann Gambin, Jesus Bertran-Gonzalez, Nicolas Vitale, Yann Humeau, Arnaud Gaudin, Sevannah A Ellis, Alysee A Michaels, Mingshan Xue, Benjamin Cravatt, Merja Joensuu, Tristan P Wallis, Frédéric A Meunier

Faculty, Staff and Students Publications

The phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning and memory, but the mechanisms through which neuronal activity affects the brain's lipid landscape remain largely unexplored. The levels of saturated FFAs, particularly of myristic acid (C14:0), strongly increase during neuronal stimulation and memory acquisition, suggesting the involvement of phospholipase A1 (PLA1) activity in synaptic plasticity. Here, we show that genetic ablation of the PLA1 isoform DDHD2 in mice dramatically reduces saturated FFA responses to memory acquisition across the brain. Furthermore, DDHD2 loss also decreases memory performance in reward-based learning and spatial memory …

Study Design And Methods: Us Study To Protect Brain Health Through Lifestyle Intervention To Reduce Risk (Us Pointer), Laura D Baker, Heather M Snyder, Mark A Espeland, Rachel A Whitmer, Miia Kivipelto, Nancy Woolard, Jeffrey Katula, Kathryn V Papp, Jennifer Ventrelle, Sarah Graef, Marcus A Hill, Scott Rushing, Julia Spell, Laura Lovato, Deborah Felton, Benjamin J Williams, Mina Ghadimi Nouran, Rema Raman, Tiia Ngandu, Alina Solomon, Sharon Wilmoth, Maryjo L Cleveland, Jeff D Williamson, Katherine L Lambert, Sarah Tomaszewski Farias, Claire E Day, Christy C Tangney, Darren R Gitelman, Olivia Matongo, Terrianne Reynolds, Valory N Pavlik, Melissa M Yu, Ashley S Alexander, Richard Elbein, Ann Marie Mcdonald, Stephen Salloway, Rena R Wing, Susan Antkowiak, Martha Clare Morris, Maria C Carrillo

Faculty, Staff and Students Publications

INTRODUCTION: The U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER) is conducted to confirm and expand the results of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in Americans.

METHODS: U.S. POINTER was planned as a 2-year randomized controlled trial of two lifestyle interventions in 2000 older adults at risk for dementia due to well-established factors. The primary outcome is a global cognition composite that permits harmonization with FINGER.

RESULTS: U.S. POINTER is centrally coordinated and conducted at five clinical sites (ClinicalTrials.gov: NCT03688126). Outcomes assessments are completed at baseline and …

Disentangling Accelerated Cognitive Decline From The Normal Aging Process And Unraveling Its Genetic Components: A Neuroimaging-Based Deep Learning Approach, Yulin Dai, Yu-Chun Hsu, Brisa S Fernandes, Kai Zhang, Xiaoyang Li, Nitesh Enduru, Andi Liu, Astrid M Manuel, Xiaoqian Jiang, Zhongming Zhao, Alzheimer’S Disease Neuroimaging Initiative

Faculty, Staff and Student Publications

BACKGROUND: The progressive cognitive decline, an integral component of Alzheimer's disease (AD), unfolds in tandem with the natural aging process. Neuroimaging features have demonstrated the capacity to distinguish cognitive decline changes stemming from typical brain aging and AD between different chronological points.

OBJECTIVE: To disentangle the normal aging effect from the AD-related accelerated cognitive decline and unravel its genetic components using a neuroimaging-based deep learning approach.

METHODS: We developed a deep-learning framework based on a dual-loss Siamese ResNet network to extract fine-grained information from the longitudinal structural magnetic resonance imaging (MRI) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. …

Circulating Sphingolipids In Relation To Cognitive Decline And Incident Dementia: The Cardiovascular Health Study, Kristine F Moseholm, Héléne T Cronjé, Manja Koch, Annette L Fitzpatrick, Oscar L Lopez, Marcia C De Oliveira Otto, W T Longstreth, Andrew N Hoofnagle, Kenneth J Mukamal, Rozenn N Lemaitre, Majken K Jensen

Faculty, Staff and Student Publications

INTRODUCTION: Whether circulating levels of sphingolipids are prospectively associated with cognitive decline and dementia risk is uncertain.

METHODS: We measured 14 sphingolipid species in plasma samples from 4488 participants (mean age 76.2 years; 40% male; and 25% apolipoprotein E (

RESULTS: Higher plasma levels of sphingomyelin-d18:1/16:0 (SM-16) were associated with a faster cognitive decline measured with 3MSE, in contrast, higher levels of sphingomyelin-d18:1/22:0 (SM-22) were associated with slower decline in cognition measured with DSST. In Cox regression, higher levels of SM-16 (hazard ration [HR] = 1.24 [95% confidence interval [CI]: 1.08-1.44]) and ceramide-d18:1/16:0 (Cer-16) (HR = 1.26 [95% CI: 1.10-1.45]) …

Association Of Circulating Ketone Bodies With Cognitive Performance And Dementia In The Multi-Ethnic Study Of Atherosclerosis (Mesa), Parag Anilkumar Chevli, Christopher L Schaich, Alexis C Wood, Luqman A Tk, Anurag Mehta, Vardhmaan Jain, Margery Connelly, Suzanne Craft, Elad Shemesh, José A Luchsinger, Kathleen M Hayden, Bonnie Colleen Sachs, Timothy M Hughes, Michael D Shapiro

Faculty, Staff and Students Publications

Introduction

Growing interest centers on the association between circulating ketone bodies (KB) and cognitive function, notably in aging and neurodegenerative diseases.

Methods

Associations of plasma KB with incident dementia and cognitive performances were examined among Multi‐Ethnic Study of Atherosclerosis (MESA) participants. KB were measured using plasma samples collected following an overnight fasting at Exam 1 (2000–02) and detailed cognitive testing at Exam 5 (2010–2012, N = 4392), Exam 6 (2016–2018, N = 1838), and in MESA‐MIND (2019–2021, N = 2060).

Results

Over 16.7 years, a doubling of total KB was associated with a greater risk of incident dementia (hazard ratio …

Establishment Of A Consensus Protocol To Explore The Brain Pathobiome In Patients With Mild Cognitive Impairment And Alzheimer’S Disease: Research Outline And Call For Collaboration, Richard Lathe, Nikki M Schultek, Brian J Balin, Garth D Ehrlich, Lavinia Alberi Auber, George Perry, Edward B Breitschwerdt, David B Corry, Richard L Doty, Robert A Rissman, Peter L Nara, Ruth Itzhaki, William A Eimer, Rudolph E Tanzi, Intracell Research Group Consortium Collaborators

Faculty, Staff and Students Publications

Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will …

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. …

A Polygenic Risk Score For Alzheimer’S Disease Constructed Using Apoe-Region Variants Has Stronger Association Than Apoe Alleles With Mild Cognitive Impairment In Hispanic/Latino Adults In The Us, Tamar Sofer, Nuzulul Kurniansyah, Einat Granot-Hershkovitz, Matthew O Goodman, Wassim Tarraf, Iris Broce, Richard B Lipton, Martha Daviglus, Melissa Lamar, Sylvia Wassertheil-Smoller, Jianwen Cai, Charles S Decarli, Hector M Gonzalez, Myriam Fornage

Faculty, Staff and Student Publications

INTRODUCTION: Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome.

METHODS: We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank.

RESULTS: A simple sum of 5 PRSs ("PRSsum"), each constructed based on a …

Oleoylethanolamide Facilitates Pparα And Tfeb Signaling And Attenuates Aβ Pathology In A Mouse Model Of Alzheimer’S Disease, Michele M Comerota, Manasee Gedam, Wen Xiong, Feng Jin, Lisheng Deng, Meng C Wang, Jin Wang, Hui Zheng

Faculty, Staff and Students Publications

BACKGROUND: Age is the strongest risk factor for the development of Alzheimer's disease (AD). Besides the pathological hallmarks of β-amyloid (Aβ) plaques and neurofibrillary tangles, emerging evidence demonstrates a critical role of microglia and neuroinflammation in AD pathogenesis. Oleoylethanolamide (OEA) is an endogenous lipid amide that has been shown to promote lifespan and healthspan in C. elegans through regulation of lysosome-to-nucleus signaling and cellular metabolism. The goal of our study was to determine the role of OEA in the mediation of microglial activity and AD pathology using its stable analog, KDS-5104.

METHODS: We used primary microglial cultures and genetic and …

Exploring Gastrointestinal Health In Mecp2 Duplication Syndrome, Davut Pehlivan, Muharrem Ak, Daniel G Glaze, Bernhard Suter, Kathleen J Motil

Faculty, Staff and Students Publications

BACKGROUND: MECP2 duplication syndrome (MDS) is a rare neurogenetic syndrome caused by duplications of MECP2 at the Xq28 region. Although constipation and gastrointestinal reflux are reported in MDS, a comprehensive characterization of gastrointestinal health has not been fully explored.

METHODS: We conducted a parent survey to explore the characteristics of gastrointestinal health in individuals with MDS using a secure online registry and compared differences in gastrointestinal symptoms between individuals with MDS and those with Rett syndrome (RTT).

KEY RESULTS: One hundred six surveys were analyzed. Symptoms commonly associated with constipation occurred in 72% to 89% of MDS individuals. Eleven percent …

Using Wearable Sensors To Measure Goal Achievement In Older Veterans With Dementia, Jennifer Freytag, Ram Kinker Mishra, Richard L Street, Angela Catic, Lilian Dindo, Lea Kiefer, Bijan Najafi, Aanand D Naik

Faculty, Staff and Students Publications

Aligning treatment with patients’ self-determined goals and health priorities is challenging in dementia care. Wearable-based remote health monitoring may facilitate determining the active participation of individuals with dementia towards achieving the determined goals. The present study aimed to demonstrate the feasibility of using wearables to assess healthcare goals set by older adults with cognitive impairment. We present four specific cases that assess (1) the feasibility of using wearables to monitor healthcare goals, (2) differences in function after goal-setting visits, and (3) goal achievement. Older veterans (n = 17) with cognitive impairment completed self-report assessments of mobility, then had an …

Smart-Home Concept For Remote Monitoring Of Instrumental Activities Of Daily Living (Iadl) In Older Adults With Cognitive Impairment: A Proof Of Concept And Feasibility Study, Myeounggon Lee, Ram Kinker Mishra, Anmol Momin, Nesreen El-Refaei, Amir Behzad Bagheri, Michele K York, Mark E Kunik, Marc Derhammer, Borna Fatehi, James Lim, Rylee Cole, Gregory Barchard, Ashkan Vaziri, Bijan Najafi

Center on Aging Staff Publications

Assessment of instrumental activities of daily living (IADL) is essential for the diagnosis and staging of dementia. However, current IADL assessments are subjective and cannot be administered remotely. We proposed a smart-home design, called IADLSys, for remote monitoring of IADL. IADLSys consists of three major components: (1) wireless physical tags (pTAG) attached to objects of interest, (2) a pendant-sensor to monitor physical activities and detect interaction with pTAGs, and (3) an interactive tablet as a gateway to transfer data to a secured cloud. Four studies, including an exploratory clinical study with five older adults with clinically confirmed cognitive impairment, who …

Covid-19 Hospital And Emergency Department Visitor Policies In The United States: Impact On Persons With Cognitive Or Physical Impairment Or Receiving End-Of-Life Care, Alexander X Lo, Logan K Wedel, Shan W Liu, Thiti Wongtangman, Phraewa Thatphet, Ilianna Santangelo, Anita N Chary, Paul D Biddinger, Corita R Grudzen, Maura Kennedy

Faculty, Staff and Students Publications

OBJECTIVE: To characterize the national distribution of COVID-19 hospital and emergency department visitor restriction policies across the United States, focusing on patients with cognitive or physical impairment or receiving end-of-life care.

METHODS: Cross-sectional study of visitor policies and exceptions, using a nationally representative random sample of EDs and hospitals during the first wave of the COVID-19 pandemic, by trained study investigators using standardized instrument.

RESULTS: Of the 352 hospitals studied, 326 (93%) had a COVID-19 hospital-wide visitor restriction policy and 164 (47%) also had an ED-specific policy. Hospital-wide policies were more prevalent at academic than non-academic (96% vs 90%;

CONCLUSION: …

Evaluating Older Adults With Cognitive Dysfunction: A Qualitative Study With Emergency Clinicians, Anita N Chary, Noelle Castilla-Ojo, Christopher Joshi, Ilianna Santangelo, Christopher R Carpenter, Kei Ouchi, Aanand D Naik, Shan W Liu, Maura Kennedy

Faculty, Staff and Students Publications

BACKGROUND: Evaluating older adults with cognitive dysfunction in emergency departments (EDs) requires obtaining collateral information from sources other than the patient. Understanding the challenges emergency clinicians face in obtaining collateral information can inform development of interventions to improve geriatric emergency care and, more specifically, detection of ED delirium. The objective was to understand emergency clinicians' experiences obtaining collateral information on older adults with cognitive dysfunction, both before and during the COVID-19 pandemic.

METHODS: From February to May 2021, we conducted semi-structured interviews with a purposive sample of 22 emergency physicians and advanced practice providers from two urban academic hospitals and …

Blood Metabolites Predicting Mild Cognitive Impairment In The Study Of Latinos-Investigation Of Neurocognitive Aging (Hchs/So), Shan He, Einat Granot-Hershkovitz, Ying Zhang, Jan Bressler, Wassim Tarraf, Bing Yu, Tianyi Huang, Donglin Zeng, Sylvia Wassertheil-Smoller, Melissa Lamar, Martha Daviglus, Maria J Marquine, Jianwen Cai, Thomas Mosley, Robert Kaplan, Eric Boerwinkle, Myriam Fornage, Charles Decarli, Bruce Kristal, Hector M Gonzalez, Tamar Sofer

Faculty, Staff and Student Publications

INTRODUCTION: Blood metabolomics-based biomarkers may be useful to predict measures of neurocognitive aging.

METHODS: We tested the association between 707 blood metabolites measured in 1451 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), with mild cognitive impairment (MCI) and global cognitive change assessed 7 years later. We further used Lasso penalized regression to construct a metabolomics risk score (MRS) that predicts MCI, potentially identifying a different set of metabolites than those discovered in individual-metabolite analysis.

RESULTS: We identified 20 metabolites predicting prevalent MCI and/or global cognitive change. Six of them were novel and 14 were previously reported as …

Dataset: Knowledge And Attitude Retention Following An Implicit Bias Classroom Workshop, Yuanyuan Zhou, Joel Purkiss, Malvika Juneja, Jocelyn Greely, Anitra Beasley, Anne Gill

Faculty, Staff and Students Publications

Background: Baylor College of Medicine provides a classroom-based implicit bias workshop to all third-year medical students to increase students’ awareness of their unconscious bias and develop strategies for reducing health care disparities. The workshop meets our immediate goals and objectives. However, we are unsure if the benefit would be long-term or diminish over time.

Methods: To examine the concept retention from the implicit bias classroom workshop, we administered a self-developed seven-item seven-point Likert-scale survey to our medical students at pre-, post-, and one-year post-workshop attendance.

Results: The data set was comprised of survey results from two cohorts of our third …

Using The Behaviour Change Wheel Program Planning Model To Design Games For Health: Development Study, Michael C Robertson, Tom Baranowski, Debbe Thompson, Karen M Basen-Engquist, Maria Chang Swartz, Elizabeth J Lyons

Faculty, Staff and Students Publications

BACKGROUND: Games for health are a promising approach to health promotion. Their success depends on achieving both experiential (game) and instrumental (health) objectives. There is little to guide game for health (G4H) designers in integrating the science of behavior change with the art of game design.

OBJECTIVE: The aim of this study is to extend the Behaviour Change Wheel program planning model to develop Challenges for Healthy Aging: Leveraging Limits for Engaging Networked Game-Based Exercise (CHALLENGE), a G4H centered on increasing physical activity in insufficiently active older women.

METHODS: We present and apply the G4H Mechanics, Experiences, and Change (MECHA) …

Variations In Medical Students' Educational Preferences, Attitudes And Volunteerism During The Covid-19 Global Pandemic, Nital P Appelbaum, Sanghamitra M Misra, Jennifer Welch, M Harrison Humphries, Sunthosh Sivam, Nadia Ismail

Faculty, Staff and Students Publications

Public health crises require individuals, often volunteers, to help minimize disasters. The COVID-19 pandemic required such activation of individuals, but little is known about medical students’ preferences of such engagement. We investigated potential variations in medical students’ educational preferences, attitudes, and volunteerism during the COVID-19 pandemic based on socio-demographics to better prepare for future activation scenarios. A web-based, anonymous survey of U.S. medical students at a single institution was conducted in May 2020. Across four training year, 518 (68% response rate) students completed the survey. During the pandemic, 42.3% (n = 215) wanted to discontinue in-person clinical experiences, 32.3% (n …

Intermittent Hypoxia And Effects On Early Learning/Memory: Exploring The Hippocampal Cellular Effects Of Pediatric Obstructive Sleep Apnea, Arvind Chandrakantan, Adam C Adler, Mehmet Tohsun, Farrah Kheradamand, Russell S Ray, Steven Roth

Faculty, Staff and Students Publications

This review provides an update on the neurocognitive phenotype of pediatric obstructive sleep apnea (OSA). Pediatric OSA is associated with neurocognitive deficits involving memory, learning, and executive functioning. Adenotonsillectomy (AT) is presently accepted as the first-line surgical treatment for pediatric OSA, but the executive function deficits do not resolve postsurgery, and the timeline for recovery remains unknown. This finding suggests that pediatric OSA potentially causes irreversible damage to multiple areas of the brain. The focus of this review is the hippocampus, 1 of the 2 major sites of postnatal neurogenesis, where new neurons are formed and integrated into existing circuitry …

The Rac-Gef Tiam1 Promotes Dendrite And Synapse Stabilization Of Dentate Granule Cells And Restricts Hippocampal-Dependent Memory Functions, Jinxuan Cheng, Federico Scala, Francisco A Blanco, Sanyong Niu, Karen Firozi, Laura Keehan, Shalaka Mulherkar, Emmanouil Froudarakis, Lingyong Li, Joseph G Duman, Xiaolong Jiang, Kimberley F Tolias

Faculty, Staff and Students Publications

The dentate gyrus (DG) controls information flow into the hippocampus and is critical for learning, memory, pattern separation, and spatial coding, while DG dysfunction is associated with neuropsychiatric disorders. Despite its importance, the molecular mechanisms regulating DG neural circuit assembly and function remain unclear. Here, we identify the Rac-GEF Tiam1 as an important regulator of DG development and associated memory processes. In the hippocampus, Tiam1 is predominantly expressed in the DG throughout life. Global deletion of Tiam1 in male mice results in DG granule cells with simplified dendritic arbors, reduced dendritic spine density, and diminished excitatory synaptic transmission. Notably, DG …