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3,478 results on '"Lopez, Oscar"'

1. Simple and Nearly-Optimal Sampling for Rank-1 Tensor Completion via Gauss-Jordan

Author

Gomez-Leos, Alejandro and López, Oscar

Subjects
Computer Science - Data Structures and Algorithms, Computer Science - Machine Learning, Mathematics - Statistics Theory, Statistics - Machine Learning
Abstract

We revisit the sample and computational complexity of completing a rank-1 tensor in $\otimes_{i=1}^{N} \mathbb{R}^{d}$, given a uniformly sampled subset of its entries. We present a characterization of the problem (i.e. nonzero entries) which admits an algorithm amounting to Gauss-Jordan on a pair of random linear systems. For example, when $N = \Theta(1)$, we prove it uses no more than $m = O(d^2 \log d)$ samples and runs in $O(md^2)$ time. Moreover, we show any algorithm requires $\Omega(d\log d)$ samples. By contrast, existing upper bounds on the sample complexity are at least as large as $d^{1.5} \mu^{\Omega(1)} \log^{\Omega(1)} d$, where $\mu$ can be $\Theta(d)$ in the worst case. Prior work obtained these looser guarantees in higher rank versions of our problem, and tend to involve more complicated algorithms., Comment: 16 pages; corrected typos in Prior Work section & Theorem 1.5

Published
2024

2. A single risk assessment for the most common diseases of ageing, developed and validated on 10 cohort studies.

Author

Huque, Md, Kootar, Scherazad, Kiely, Kim, Anderson, Craig, van Boxtel, Martin, Brodaty, Henry, Sachdev, Perminder, Carlson, Michelle, Fitzpatrick, Annette, Whitmer, Rachel, Kivipelto, Miia, Jorm, Louisa, Köhler, Sebastian, Lautenschlager, Nicola, Lopez, Oscar, Shaw, Jonathan, Matthews, Fiona, Peters, Ruth, and Anstey, Kaarin

Subjects
Dementia, Diabetes, Heart attack, Primary prevention, Risk factors, Risk prediction, Risk tool, Stroke, Humans, Aged, Risk Assessment, Male, Female, Cohort Studies, Aged, 80 and over, Dementia, Diabetes Mellitus, Myocardial Infarction, Stroke, Risk Factors, Aging
Abstract

BACKGROUND: We aimed to develop risk tools for dementia, stroke, myocardial infarction (MI), and diabetes, for adults aged ≥ 65 years using shared risk factors. METHODS: Data were obtained from 10 population-based cohorts (N = 41,755) with median follow-up time (years) for dementia, stroke, MI, and diabetes of 6.2, 7.0, 6.8, and 7.4, respectively. Disease-free participants at baseline were included, and 22 risk factors (sociodemographic, medical, lifestyle, laboratory biomarkers) were evaluated. Two risk tools (DemNCD and DemNCD-LR based on Fine and Gray sub-distribution and logistic regression [LR], respectively) were developed and validated. Predictive accuracies of these risk tools were assessed using Harrels C-statistics and area under the curve (AUC) and 95% confidence interval (CI). Model calibration was conducted using Hosmer-Lemeshow goodness of fit test along calibration plots. RESULTS: Both the DemNCD and DemNCD-LR resulted in similar predictive accuracy for each outcome. The overall AUC (95% CI) for dementia, stroke, MI, and diabetes risk tool were 0·68 (0·65, 0·70), 0·58 (0·54, 0·61), 0·65 (0·61, 0·68), and 0·68 (0·64, 0·72), respectively, for males. For females, these figures were 0·65 (0·63, 0·67), 0·55 (0·52, 0·57), 0·65 (0·62, 0·68), and 0·61 (0·57, 0·65). CONCLUSIONS: The DemNCD is the first tool to predict both dementia and multiple cardio-metabolic diseases using comprehensive risk factors and provided similar predictive accuracy to existing risk tools. It has similar predictive accuracy as tools designed for single outcomes in this age-group. DemNCD has the potential to be used in community and clinical settings as it includes self-reported and routinely available clinical measures.

Published
2024

3. X‐chromosome-wide association study for Alzheimer’s disease

Author

Le Borgne, Julie, Gomez, Lissette, Heikkinen, Sami, Amin, Najaf, Ahmad, Shahzad, Choi, Seung Hoan, Bis, Joshua, Grenier-Boley, Benjamin, Rodriguez, Omar Garcia, Kleineidam, Luca, Young, Juan, Tripathi, Kumar Parijat, Wang, Lily, Varma, Achintya, Campos-Martin, Rafael, van der Lee, Sven, Damotte, Vincent, de Rojas, Itziar, Palmal, Sagnik, Lipton, Richard, Reiman, Eric, McKee, Ann, De Jager, Philip, Bush, William, Small, Scott, Levey, Allan, Saykin, Andrew, Foroud, Tatiana, Albert, Marilyn, Hyman, Bradley, Petersen, Ronald, Younkin, Steven, Sano, Mary, Wisniewski, Thomas, Vassar, Robert, Schneider, Julie, Henderson, Victor, Roberson, Erik, DeCarli, Charles, LaFerla, Frank, Brewer, James, Swerdlow, Russell, Van Eldik, Linda, Hamilton-Nelson, Kara, Paulson, Henry, Naj, Adam, Lopez, Oscar, Chui, Helena, Crane, Paul, Grabowski, Thomas, Kukull, Walter, Asthana, Sanjay, Craft, Suzanne, Strittmatter, Stephen, Cruchaga, Carlos, Leverenz, James, Goate, Alison, Kamboh, M. Ilyas, George-Hyslop, Peter St, Valladares, Otto, Kuzma, Amanda, Cantwell, Laura, Riemenschneider, Matthias, Morris, John, Slifer, Susan, Dalmasso, Carolina, Castillo, Atahualpa, Küçükali, Fahri, Peters, Oliver, Schneider, Anja, Dichgans, Martin, Rujescu, Dan, Scherbaum, Norbert, Deckert, Jürgen, Riedel-Heller, Steffi, Hausner, Lucrezia, Molina-Porcel, Laura, Düzel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie, Moebus, Susanne, Tegos, Thomas, Scarmeas, Nikolaos, Dols-Icardo, Oriol, Moreno, Fermin, Pérez-Tur, Jordi, Bullido, María J., Pastor, Pau, Sánchez-Valle, Raquel, Álvarez, Victoria, Boada, Mercè, García-González, Pablo, Puerta, Raquel, Mir, Pablo, Real, Luis M., Piñol-Ripoll, Gerard, García-Alberca, Jose María, Royo, Jose Luís, Rodriguez-Rodriguez, Eloy, Soininen, Hilkka, de Mendonça, Alexandre, Mehrabian, Shima, Traykov, Latchezar, Hort, Jakub, Vyhnalek, Martin, Thomassen, Jesper Qvist, Pijnenburg, Yolande A. L., Holstege, Henne, van Swieten, John, Ramakers, Inez, Verhey, Frans, Scheltens, Philip, Graff, Caroline, Papenberg, Goran, Giedraitis, Vilmantas, Boland, Anne, Deleuze, Jean-François, Nicolas, Gael, Dufouil, Carole, Pasquier, Florence, Hanon, Olivier, Debette, Stéphanie, Grünblatt, Edna, Popp, Julius, Ghidoni, Roberta, Galimberti, Daniela, Arosio, Beatrice, Mecocci, Patrizia, Solfrizzi, Vincenzo, Parnetti, Lucilla, Squassina, Alessio, Tremolizzo, Lucio, Borroni, Barbara, Nacmias, Benedetta, Spallazzi, Marco, Seripa, Davide, Rainero, Innocenzo, Daniele, Antonio, Bossù, Paola, Masullo, Carlo, Rossi, Giacomina, Jessen, Frank, Fernandez, Victoria, Kehoe, Patrick Gavin, Frikke-Schmidt, Ruth, Tsolaki, Magda, Sánchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Haines, Jonathan, Farrer, Lindsay, Mayeux, Richard, Wang, Li-San, Sims, Rebecca, DeStefano, Anita, Schellenberg, Gerard D., Seshadri, Sudha, Amouyel, Philippe, Williams, Julie, van der Flier, Wiesje, Ramirez, Alfredo, Pericak-Vance, Margaret, Andreassen, Ole A., Van Duijn, Cornelia, Hiltunen, Mikko, Ruiz, Agustín, Dupuis, Josée, Martin, Eden, Lambert, Jean-Charles, Kunkle, Brian, and Bellenguez, Céline

Published
2024
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4. Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries

Author

García-Marín, Luis M., Campos, Adrian I., Diaz-Torres, Santiago, Rabinowitz, Jill A., Ceja, Zuriel, Mitchell, Brittany L., Grasby, Katrina L., Thorp, Jackson G., Agartz, Ingrid, Alhusaini, Saud, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arfanakis, Konstantinos, Arias-Vasquez, Alejandro, Armstrong, Nicola J., Athanasiu, Lavinia, Bastin, Mark E., Beiser, Alexa S., Bennett, David A., Bis, Joshua C., Boks, Marco P. M., Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Burkhardt, Ralph, Cahn, Wiepke, Calhoun, Vince D., Carmichael, Owen T., Chakravarty, Mallar, Chen, Qiang, Ching, Christopher R. K., Cichon, Sven, Crespo-Facorro, Benedicto, Crivello, Fabrice, Dale, Anders M., Smith, George Davey, de Geus, Eco J. C., De Jager, Philip L., de Zubicaray, Greig I., Debette, Stéphanie, DeCarli, Charles, Depondt, Chantal, Desrivières, Sylvane, Djurovic, Srdjan, Ehrlich, Stefan, Erk, Susanne, Espeseth, Thomas, Fernández, Guillén, Filippi, Irina, Fisher, Simon E., Fleischman, Debra A., Fletcher, Evan, Fornage, Myriam, Forstner, Andreas J., Francks, Clyde, Franke, Barbara, Ge, Tian, Goldman, Aaron L., Grabe, Hans J., Green, Robert C., Grimm, Oliver, Groenewold, Nynke A., Gruber, Oliver, Gudnason, Vilmundur, Håberg, Asta K., Haukvik, Unn K., Heinz, Andreas, Hibar, Derrek P., Hilal, Saima, Himali, Jayandra J., Ho, Beng-Choon, Hoehn, David F., Hoekstra, Pieter J., Hofer, Edith, Hoffmann, Wolfgang, Holmes, Avram J., Homuth, Georg, Hosten, Norbert, Ikram, M. Kamran, Ipser, Jonathan C., Jack Jr, Clifford R., Jahanshad, Neda, Jönsson, Erik G., Kahn, Rene S., Kanai, Ryota, Klein, Marieke, Knol, Maria J., Launer, Lenore J., Lawrie, Stephen M., Hellard, Stephanie Le, Lee, Phil H., Lemaître, Hervé, Li, Shuo, Liewald, David C. M., Lin, Honghuang, Longstreth, Jr, W. T., Lopez, Oscar L., Luciano, Michelle, Maillard, Pauline, Marquand, Andre F., Martin, Nicholas G., Martinot, Jean-Luc, Mather, Karen A., Mattay, Venkata S., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mirza-Schreiber, Nazanin, Milaneschi, Yuri, Mosley, Thomas H., Mühleisen, Thomas W., Müller-Myhsok, Bertram, Maniega, Susana Muñoz, Nauck, Matthias, Nho, Kwangsik, Niessen, Wiro J., Nöthen, Markus M., Nyquist, Paul A., Oosterlaan, Jaap, Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Psaty, Bruce M., Pütz, Benno, Reppermund, Simone, Rietschel, Marcella D., Risacher, Shannon L., Romanczuk-Seiferth, Nina, Romero-Garcia, Rafael, Roshchupkin, Gennady V., Rotter, Jerome I., Sachdev, Perminder S., Sämann, Philipp G., Saremi, Arvin, Sargurupremraj, Muralidharan, Saykin, Andrew J., Schmaal, Lianne, Schmidt, Helena, Schmidt, Reinhold, Schofield, Peter R., Scholz, Markus, Schumann, Gunter, Schwarz, Emanuel, Shen, Li, Shin, Jean, Sisodiya, Sanjay M., Smith, Albert V., Smoller, Jordan W., Soininen, Hilkka S., Steen, Vidar M., Stein, Dan J., Stein, Jason L., Thomopoulos, Sophia I., Toga, Arthur W., Tordesillas-Gutiérrez, Diana, Trollor, Julian N., Valdes-Hernandez, Maria C., van ′t Ent, Dennis, van Bokhoven, Hans, van der Meer, Dennis, van der Wee, Nic J. A., Vázquez-Bourgon, Javier, Veltman, Dick J., Vernooij, Meike W., Villringer, Arno, Vinke, Louis N., Völzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westlye, Lars T., Westman, Eric, White, Tonya, Witte, A. Veronica, Wolf, Christiane, Yang, Jingyun, Zwiers, Marcel P., Ikram, M. Arfan, Seshadri, Sudha, Thompson, Paul M., Satizabal, Claudia L., Medland, Sarah E., and Rentería, Miguel E.

Published
2024
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5. Pulmonary Parenchyma and COVID-19 Lesion Volumetric Segmentation Based on Probabilistic Active Contours

Author

Liñan-López, Oscar I., Olivares-Romo, Adrian D., Torres-Ortega, Hermes S., Rodríguez-Obregón, Diomar E., Mejía-Rodríguez, Aldo R., Magjarević, Ratko, Series Editor, Ładyżyński, Piotr, Associate Editor, Ibrahim, Fatimah, Associate Editor, Lackovic, Igor, Associate Editor, Rock, Emilio Sacristan, Associate Editor, Flores Cuautle, José de Jesús Agustín, editor, Benítez-Mata, Balam, editor, Reyes-Lagos, José Javier, editor, Hernandez Acosta, Humiko Yahaira, editor, Ames Lastra, Gerardo, editor, Zuñiga-Aguilar, Esmeralda, editor, Del Hierro-Gutierrez, Edgar, editor, and Salido-Ruiz, Ricardo Antonio, editor

Published
2025
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7. Fractureability Level of Five Composite Resins. In Vitro Study

Author

Calsín, Madelaine Huánuco, Apaza, Carol Larico, Vilca, Russel Allidren Lozada, López, Oscar Mauricio Flores, Frias, José Oscar Huanca, Pampa Vilca, Wilson Jose, Kacprzyk, Janusz, Series Editor, Novikov, Dmitry A., Editorial Board Member, Shi, Peng, Editorial Board Member, Cao, Jinde, Editorial Board Member, Polycarpou, Marios, Editorial Board Member, Pedrycz, Witold, Editorial Board Member, Alareeni, Bahaaeddin, editor, and Elgedawy, Islam, editor

Published
2025
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8. The Average Spectrum Norm and Near-Optimal Tensor Completion

Author

López, Oscar, Lehoucq, Richard, Llosa-Vite, Carlos, Prasadan, Arvind, and Dunlavy, Daniel M.

Subjects
Computer Science - Information Theory
Abstract

We introduce a new tensor norm, the average spectrum norm, to study sample complexity of tensor completion problems based on the canonical polyadic decomposition (CPD). Properties of the average spectrum norm and its dual norm are investigated, demonstrating their utility for low-rank tensor recovery analysis. Our novel approach significantly reduces the provable sample rate for CPD-based noisy tensor completion, providing the best bounds to date on the number of observed noisy entries required to produce an arbitrarily accurate estimate of an underlying mean value tensor. Under Poisson and Bernoulli multivariate distributions, we show that an $N$-way CPD rank-$R$ parametric tensor $\boldsymbol{\mathscr{M}}\in\mathbb{R}^{I\times \cdots\times I}$ generating noisy observations can be approximated by large likelihood estimators from $\mathcal{O}(IR^2\log^{N+2}(I))$ revealed entries. Furthermore, under nonnegative and orthogonal versions of the CPD we improve the result to depend linearly on the rank, achieving the near-optimal rate $\mathcal{O}(IR\log^{N+2}(I))$., Comment: Error, in Section 2.1.2

Published
2024

9. Genetic variants for head size share genes and pathways with cancer

Author

Knol, Maria J, Poot, Raymond A, Evans, Tavia E, Satizabal, Claudia L, Mishra, Aniket, Sargurupremraj, Muralidharan, van der Auwera, Sandra, Duperron, Marie-Gabrielle, Jian, Xueqiu, Hostettler, Isabel C, van Dam-Nolen, Dianne HK, Lamballais, Sander, Pawlak, Mikolaj A, Lewis, Cora E, Carrion-Castillo, Amaia, van Erp, Theo GM, Reinbold, Céline S, Shin, Jean, Scholz, Markus, Håberg, Asta K, Kämpe, Anders, Li, Gloria HY, Avinun, Reut, Atkins, Joshua R, Hsu, Fang-Chi, Amod, Alyssa R, Lam, Max, Tsuchida, Ami, Teunissen, Mariël WA, Aygün, Nil, Patel, Yash, Liang, Dan, Beiser, Alexa S, Beyer, Frauke, Bis, Joshua C, Bos, Daniel, Bryan, R Nick, Bülow, Robin, Caspers, Svenja, Catheline, Gwenaëlle, Cecil, Charlotte AM, Dalvie, Shareefa, Dartigues, Jean-François, DeCarli, Charles, Enlund-Cerullo, Maria, Ford, Judith M, Franke, Barbara, Freedman, Barry I, Friedrich, Nele, Green, Melissa J, Haworth, Simon, Helmer, Catherine, Hoffmann, Per, Homuth, Georg, Ikram, M Kamran, Jack, Clifford R, Jahanshad, Neda, Jockwitz, Christiane, Kamatani, Yoichiro, Knodt, Annchen R, Li, Shuo, Lim, Keane, Longstreth, WT, Macciardi, Fabio, Consortium, The Cohorts for Heart and Aging Research in Genomic Epidemiology, Amouyel, Philippe, Arfanakis, Konstantinos, Aribisala, Benjamin S, Bastin, Mark E, Chauhan, Ganesh, Chen, Christopher, Cheng, Ching-Yu, de Jager, Philip L, Deary, Ian J, Fleischman, Debra A, Gottesman, Rebecca F, Gudnason, Vilmundur, Hilal, Saima, Hofer, Edith, Janowitz, Deborah, Jukema, J Wouter, Liewald, David CM, Lopez, Lorna M, Lopez, Oscar, Luciano, Michelle, Martinez, Oliver, Niessen, Wiro J, Nyquist, Paul, Rotter, Jerome I, Rundek, Tatjana, Sacco, Ralph L, Schmidt, Helena, Tiemeier, Henning, Trompet, Stella, van der Grond, Jeroen, Völzke, Henry, Wardlaw, Joanna M, Yanek, Lisa, Yang, Jingyun, and Consortium, The Enhancing NeuroImaging Genetics through Meta-Analysis

Subjects
Biomedical and Clinical Sciences, Stem Cell Research, Human Genome, Cancer, Genetics, Neurosciences, Biotechnology, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Neurological, Humans, Genome-Wide Association Study, Head, Neoplasms, Female, Male, Polymorphism, Single Nucleotide, Genetic Variation, Organ Size, Signal Transduction, Adult, Genetic Predisposition to Disease, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium, cancer, genetics, genome-wide association study, head circumference, head size, intracranial volume, meta-analysis, Biomedical and clinical sciences
Abstract

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.

Published
2024

10. A positional statistic for 1324-avoiding permutations

Author

Gil, Juan B., Lopez, Oscar A., and Weiner, Michael D.

Subjects
Mathematics - Combinatorics, 05A05
Abstract

We consider the class $S_n(1324)$ of permutations of size $n$ that avoid the pattern 1324 and examine the subset $S_n^{a\prec n}(1324)$ of elements for which $a\prec n\prec [a-1]$, $a\ge 1$. This notation means that, when written in one line notation, such a permutation must have $a$ to the left of $n$, and the elements of $\{1,\dots,a-1\}$ must all be to the right of $n$. For $n\ge 2$, we establish a connection between the subset of permutations in $S_n^{1\prec n}(1324)$ having the 1 adjacent to the $n$ (called primitives), and the set of 1324-avoiding dominoes with $n-2$ points. For $a\in\{1,2\}$, we introduce constructive algorithms and give formulas for the enumeration of $S_n^{a\prec n}(1324)$ by the position of $a$ relative to the position of $n$. For $a\ge 3$, we formulate some conjectures for the corresponding generating functions., Comment: 10 pages. Final version

Published
2023
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11. 3D seismic survey design by maximizing the spectral gap

Author

Zhang, Yijun, Yin, Ziyi, López, Oscar, Siahkoohi, Ali, Louboutin, Mathias, and Herrmann, Felix J.

Subjects
Physics - Geophysics
Abstract

The massive cost of 3D acquisition calls for methods to reduce the number of receivers by designing optimal receiver sampling masks. Recent studies on 2D seismic showed that maximizing the spectral gap of the subsampling mask leads to better wavefield reconstruction results. We enrich the current study by proposing a simulation-free method to generate optimal 3D acquisition by maximizing the spectral gap of the subsampling mask via a simulated annealing algorithm. Numerical experiments confirm improvement of the proposed method over receiver sampling locations obtained by jittered sampling.

Published
2023
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12. Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer’s disease

Author

Zeng, Xuemei, Lafferty, Tara K., Sehrawat, Anuradha, Chen, Yijun, Ferreira, Pamela C. L., Bellaver, Bruna, Povala, Guilherme, Kamboh, M. Ilyas, Klunk, William E., Cohen, Ann D., Lopez, Oscar L., Ikonomovic, Milos D., Pascoal, Tharick A., Ganguli, Mary, Villemagne, Victor L., Snitz, Beth E., and Karikari, Thomas K.

Published
2024
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13. CYP1B1-RMDN2 Alzheimer’s disease endophenotype locus identified for cerebral tau PET

Author

Nho, Kwangsik, Risacher, Shannon L., Apostolova, Liana G., Bice, Paula J., Brosch, Jared R., Deardorff, Rachael, Faber, Kelley, Farlow, Martin R., Foroud, Tatiana, Gao, Sujuan, Rosewood, Thea, Kim, Jun Pyo, Nudelman, Kelly, Yu, Meichen, Aisen, Paul, Sperling, Reisa, Hooli, Basavaraj, Shcherbinin, Sergey, Svaldi, Diana, Jack, Jr., Clifford R., Jagust, William J., Landau, Susan, Vasanthakumar, Aparna, Waring, Jeffrey F., Doré, Vincent, Laws, Simon M., Masters, Colin L., Porter, Tenielle, Rowe, Christopher C., Villemagne, Victor L., Dumitrescu, Logan, Hohman, Timothy J., Libby, Julia B., Mormino, Elizabeth, Buckley, Rachel F., Johnson, Keith, Yang, Hyun-Sik, Petersen, Ronald C., Ramanan, Vijay K., Ertekin-Taner, Nilüfer, Vemuri, Prashanthi, Cohen, Ann D., Fan, Kang-Hsien, Kamboh, M. Ilyas, Lopez, Oscar L., Bennett, David A., Ali, Muhammad, Benzinger, Tammie, Cruchaga, Carlos, Hobbs, Diana, De Jager, Philip L., Fujita, Masashi, Jadhav, Vaishnavi, Lamb, Bruce T., Tsai, Andy P., Castanho, Isabel, Mill, Jonathan, Weiner, Michael W., and Saykin, Andrew J.

Published
2024
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15. Alzheimer blood biomarkers: practical guidelines for study design, sample collection, processing, biobanking, measurement and result reporting

Author

Zeng, Xuemei, Chen, Yijun, Sehrawat, Anuradha, Lee, Jihui, Lafferty, Tara K., Kofler, Julia, Berman, Sarah B., Sweet, Robert A., Tudorascu, Dana L., Klunk, William E., Ikonomovic, Milos D., Pfister, Anna, Zetterberg, Henrik, Snitz, Beth E., Cohen, Anne D., Villemagne, Victor L., Pascoal, Tharick A., Kamboh, M. llyas, Lopez, Oscar I., Blennow, Kaj, and Karikari, Thomas K.

Published
2024
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16. Varoglutamstat: Inhibiting Glutaminyl Cyclase as a Novel Target of Therapy in Early Alzheimers Disease.

Author

Feldman, Howard, Messer, Karen, Qiu, Yuqi, Sabbagh, Marwan, Galasko, Douglas, Turner, R, Lopez, Oscar, Smith, Amanda, Durant, January, Lupo, Jody-Lynn, Revta, Carolyn, Balasubramanian, Archana, Kuehn-Wache, Kerstin, Wassmann, Tanja, Schell-Mader, Sylvia, Jacobs, Diane, Salmon, David, Léger, Gabriel, DeMarco, Mari, and Weber, Frank

Subjects
Alzheimer’s disease, CCL2, N3pE-Aβ, QPCT, QPCTL, amyloid β-peptides, cerebrospinal fluid, glutaminyl cyclase, mild cognitive impairment, pGlu-Aβ, Aged, Female, Humans, Male, Alzheimer Disease, Aminoacyltransferases, Amyloid beta-Peptides, Randomized Controlled Trials as Topic, Clinical Trials, Phase II as Topic
Abstract

BACKGROUND: Varoglutamstat is a first-in-class, small molecule being investigated as a treatment for early Alzheimers disease (AD). It is an inhibitor of glutaminyl cyclase (QC), the enzyme that post-translationally modifies amyloid-β (Aβ) peptides into a toxic form of pyroglutamate Aβ (pGlu-Aβ) and iso-QC which post-translationally modifies cytokine monocyte chemoattractant protein-1 (CCL2) into neuroinflammatory pGlu-CCL2. Early phase clinical trials identified dose margins for safety and tolerability of varoglutamstat and biomarker data supporting its potential for clinical efficacy in early AD. OBJECTIVE: Present the scientific rationale of varoglutamstat in the treatment of early AD and the methodology of the VIVA-MIND (NCT03919162) trial, which uses a seamless phase 2A-2B design. Our review also includes other pharmacologic approaches to pGlu-Aβ. METHODS: Phase 2A of the VIVA-MIND trial will determine the highest dose of varoglutamstat that is safe and well tolerated with sufficient plasma exposure and a calculated target occupancy. Continuous safety evaluation using a pre-defined safety stopping boundary will help determine the highest tolerated dose that will carry forward into phase 2B. An interim futility analysis of cognitive function and electroencephalogram changes will be conducted to inform the decision of whether to proceed with phase 2B. Phase 2B will assess the efficacy and longer-term safety of the optimal selected phase 2A dose through 72 weeks of treatment. CONCLUSIONS: Varoglutamstat provides a unique dual mechanism of action addressing multiple pathogenic contributors to the disease cascade. VIVA-MIND provides a novel and efficient trial design to establish its optimal dosing, safety, tolerability, and efficacy in early AD.

Published
2024

17. Neuropsychiatric Symptoms and Microglial Activation in Patients with Alzheimer Disease

Author

Aguzzoli, Cristiano Schaffer, Ferreira, Pâmela CL, Povala, Guilherme, Ferrari-Souza, João Pedro, Bellaver, Bruna, Katz, Carolina Soares, Zalzale, Hussein, Lussier, Firoza Z, Rohden, Francieli, Abbas, Sarah, Leffa, Douglas T, Medeiros, Marina Scop, Therriault, Joseph, Benedet, Andréa L, Tissot, Cécile, Servaes, Stijn, Rahmouni, Nesrine, Macedo, Arthur Cassa, Bezgin, Gleb, Kang, Min Su, Stevenson, Jenna, Pallen, Vanessa, Cohen, Ann, Lopez, Oscar L, Tudorascu, Dana L, Klunk, William E, Villemagne, Victor L, Soucy, Jean Paul, Zimmer, Eduardo R, Schilling, Lucas P, Karikari, Thomas K, Ashton, Nicholas J, Zetterberg, Henrik, Blennow, Kaj, Gauthier, Serge, Valcour, Victor, Miller, Bruce L, Rosa-Neto, Pedro, and Pascoal, Tharick A

Subjects
Health Services and Systems, Health Sciences, Aging, Alzheimer's Disease, Brain Disorders, Acquired Cognitive Impairment, Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurosciences, Biomedical Imaging, Neurodegenerative, Clinical Research, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Male, Humans, Female, Aged, Alzheimer Disease, Microglia, tau Proteins, Cross-Sectional Studies, Amyloid beta-Peptides, Biomarkers, Biomedical and clinical sciences, Health sciences
Abstract

ImportanceNeuropsychiatric symptoms are commonly encountered and are highly debilitating in patients with Alzheimer disease. Understanding their underpinnings has implications for identifying biomarkers and treatment for these symptoms.ObjectiveTo evaluate whether glial markers are associated with neuropsychiatric symptoms in individuals across the Alzheimer disease continuum.Design, setting, and participantsThis cross-sectional study was conducted from January to June 2023, leveraging data from the Translational Biomarkers in Aging and Dementia cohort at McGill University, Canada. Recruitment was based on referrals of individuals from the community or from outpatient clinics. Exclusion criteria included active substance abuse, major surgery, recent head trauma, safety contraindications for positron emission tomography (PET) or magnetic resonance imaging, being currently enrolled in other studies, and having inadequately treated systemic conditions.Main outcomes and measuresAll individuals underwent assessment for neuropsychiatric symptoms (Neuropsychiatry Inventory Questionnaire [NPI-Q]), and imaging for microglial activation ([11C]PBR28 PET), amyloid-β ([18F]AZD4694 PET), and tau tangles ([18F]MK6240 PET).ResultsOf the 109 participants, 72 (66%) were women and 37 (34%) were men; the median age was 71.8 years (range, 38.0-86.5 years). Overall, 70 had no cognitive impairment and 39 had cognitive impairment (25 mild; 14 Alzheimer disease dementia). Amyloid-β PET positivity was present in 21 cognitively unimpaired individuals (30%) and in 31 cognitively impaired individuals (79%). The NPI-Q severity score was associated with microglial activation in the frontal, temporal, and parietal cortices (β = 7.37; 95% CI, 1.34-13.41; P = .01). A leave-one-out approach revealed that irritability was the NPI-Q domain most closely associated with the presence of brain microglial activation (β = 6.86; 95% CI, 1.77-11.95; P = .008). Furthermore, we found that microglia-associated irritability was associated with study partner burden measured by NPI-Q distress score (β = 5.72; 95% CI, 0.33-11.10; P = .03).Conclusions and relevanceIn this cross-sectional study of 109 individuals across the AD continuum, microglial activation was associated with and a potential biomarker of neuropsychiatric symptoms in Alzheimer disease. Moreover, our findings suggest that the combination of amyloid-β- and microglia-targeted therapies could have an impact on relieving these symptoms.

Published
2023

18. Spectral gap-based deterministic tensor completion

Author

Harris, Kameron Decker, López, Oscar, Read, Angus, and Zhu, Yizhe

Subjects
Statistics - Machine Learning, Computer Science - Machine Learning
Abstract

Tensor completion is a core machine learning algorithm used in recommender systems and other domains with missing data. While the matrix case is well-understood, theoretical results for tensor problems are limited, particularly when the sampling patterns are deterministic. Here we bound the generalization error of the solutions of two tensor completion methods, Poisson loss and atomic norm minimization, providing tighter bounds in terms of the target tensor rank. If the ground-truth tensor is order $t$ with CP-rank $r$, the dependence on $r$ is improved from $r^{2(t-1)(t^2-t-1)}$ in arXiv:1910.10692 to $r^{2(t-1)(3t-5)}$. The error in our bounds is deterministically controlled by the spectral gap of the sampling sparsity pattern. We also prove several new properties for the atomic tensor norm, reducing the rank dependence from $r^{3t-3}$ in arXiv:1711.04965 to $r^{3t-5}$ under random sampling schemes. A limitation is that atomic norm minimization, while theoretically interesting, leads to inefficient algorithms. However, numerical experiments illustrate the dependence of the reconstruction error on the spectral gap for the practical max-quasinorm, ridge penalty, and Poisson loss minimization algorithms. This view through the spectral gap is a promising window for further study of tensor algorithms., Comment: In proceedings of SampTA 2023

Published
2023

19. ATN cerebrospinal fluid biomarkers in dementia with Lewy bodies: Initial results from the United States Dementia with Lewy Bodies Consortium

Author

Jain, Lavanya, Khrestian, Maria, Formica, Shane, Tuason, Elizabeth D, Pillai, Jagan A, Rao, Stephen, Oguh, Odinachi, Lippa, Carol F, Lopez, Oscar L, Berman, Sarah B, Tsuang, Debby W, Zabetian, Cyrus P, Irwin, David J, Galasko, Douglas R, Litvan, Irene, Marder, Karen S, Honig, Lawrence S, Fleisher, Jori E, Galvin, James E, Bozoki, Andrea C, Taylor, Angela S, Sabbagh, Marwan N, Leverenz, James B, and Bekris, Lynn M

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Lewy Body Dementia, Aging, Acquired Cognitive Impairment, Alzheimer's Disease, Brain Disorders, Dementia, Alzheimer's Disease Related Dementias (ADRD), Clinical Research, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurological, ATN longitudinal data, ATN research framework, cerebrospinal fluid biomarkers, dementia with Lewy bodies, neuropathology, pre-mortem ATN status, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionThe National Institute on Aging - Alzheimer's Association (NIA-AA) ATN research framework proposes to use biomarkers for amyloid (A), tau (T), and neurodegeneration (N) to stage individuals with AD pathological features and track changes longitudinally. The overall aim was to utilize this framework to characterize pre-mortem ATN status longitudinally in a clinically diagnosed cohort of dementia with Lewy bodies (DLB) and to correlate it with the post mortem diagnosis.MethodsThe cohort was subtyped by cerebrospinal fluid (CSF) ATN category. A subcohort had longitudinal data, and a subgroup was neuropathologically evaluated.ResultsWe observed a significant difference in Aβ42/40 after 12 months in the A+T- group. Post mortem neuropathologic analyses indicated that most of the p-Tau 181 positive (T+) cases also had a high Braak stage.DiscussionThis suggests that DLB patients who are A+ but T- may need to be monitored to determine whether they remain A+ or ever progress to T positivity.HighlightsSome A+T- DLB subjects transition from A+ to negative after 12-months. Clinically diagnosed DLB with LBP-AD (A+T+) maintain their positivity. Clinically diagnosed DLB with LBP-AD (A+T+) maintain their positivity. Monitoring of the A+T- sub-type of DLB may be necessary.

Published
2023

20. LATE-NC risk alleles (in TMEM106B, GRN, and ABCC9 genes) among persons with African ancestry.

Author

Katsumata, Yuriko, Fardo, David W, Shade, Lincoln MP, Bowen, James D, Crane, Paul K, Jarvik, Gail P, Keene, C Dirk, Larson, Eric B, McCormick, Wayne C, McCurry, Susan M, Mukherjee, Shubhabrata, Kowall, Neil W, McKee, Ann C, Honig, Robert A, Lawrence, S, Vonsattel, Jean Paul, Williamson, Jennifer, Small, Scott, Burke, James R, Hulette, Christine M, Welsh-Bohmer, Kathleen A, Gearing, Marla, Lah, James J, Levey, Allan I, Wingo, Thomas S, Apostolova, Liana G, Farlow, Martin R, Ghetti, Bernardino, Saykin, Andrew J, Spina, Salvatore, Albert, Marilyn S, Lyketsos, Constantine G, Troncoso, Juan C, Frosch, Matthew P, Green, Robert C, Growdon, John H, Hyman, Bradley T, Tanzi, Rudolph E, Potter, Huntington, Dickson, Dennis W, Ertekin-Taner, Nilufer, Graff-Radford, Neill R, Parisi, Joseph E, Petersen, Ronald C, Duara, Ranjan, Buxbaum, Joseph D, Goate, Alison M, Sano, Mary, Masurkar, Arjun V, Wisniewski, Thomas, Bigio, Eileen H, Mesulam, Marsel, Weintraub, Sandra, Vassar, Robert, Kaye, Jeffrey A, Quinn, Joseph F, Woltjer, Randall L, Barnes, Lisa L, Bennett, David A, Schneider, Julie A, Yu, Lei, Henderson, Victor, Fallon, Kenneth B, Harrell, Lindy E, Marson, Daniel C, Roberson, Erik D, DeCarli, Charles, Jin, Lee-Way, Olichney, John M, Kim, Ronald, LaFerla, Frank M, Monuki, Edwin, Head, Elizabeth, Sultzer, David, Geschwind, Daniel H, Vinters, Harry V, Chesselet, Marie-Francoise, Galasko, Douglas R, Brewer, James B, Boxer, Adam, Karydas, Anna, Kramer, Joel H, Miller, Bruce L, Rosen, Howard J, Seeley, William W, Burns, Jeffrey M, Swerdlow, Russell H, Abner, Erin, Van Eldik, Linda J, Albin, Roger L, Lieberman, Andrew P, Paulson, Henry L, Arnold, Steven E, Trojanowski, John Q, Van Deerlin, Vivianna M, Hamilton, Ronald L, Kamboh, M Ilyas, Lopez, Oscar L, and Becker, James T

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Aging, Prevention, Neurodegenerative, Acquired Cognitive Impairment, Alzheimer's Disease, Dementia, Minority Health, Health Disparities, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Genetics, 2.1 Biological and endogenous factors, Humans, Alleles, Polymorphism, Single Nucleotide, Alzheimer Disease, TDP-43 Proteinopathies, Progranulins, Membrane Proteins, Nerve Tissue Proteins, Sulfonylurea Receptors, Alzheimer’s Disease Genetics Consortium, KCNMB2, Diversity, Epidemiology, FTLD, Genome-Wide Association Studies, KATP, Neurology & Neurosurgery, Clinical sciences
Abstract

Limbic-predominant age-related TDP-43 encephalopathy (LATE) affects approximately one-third of older individuals and is associated with cognitive impairment. However, there is a highly incomplete understanding of the genetic determinants of LATE neuropathologic changes (LATE-NC) in diverse populations. The defining neuropathologic feature of LATE-NC is TDP-43 proteinopathy, often with comorbid hippocampal sclerosis (HS). In terms of genetic risk factors, LATE-NC and/or HS are associated with single nucleotide variants (SNVs) in 3 genes-TMEM106B (rs1990622), GRN (rs5848), and ABCC9 (rs1914361 and rs701478). We evaluated these 3 genes in convenience samples of individuals of African ancestry. The allele frequencies of the LATE-associated alleles were significantly different between persons of primarily African (versus European) ancestry: In persons of African ancestry, the risk-associated alleles for TMEM106B and ABCC9 were less frequent, whereas the risk allele in GRN was more frequent. We performed an exploratory analysis of data from African-American subjects processed by the Alzheimer's Disease Genomics Consortium, with a subset of African-American participants (n = 166) having corroborating neuropathologic data through the National Alzheimer's Coordinating Center (NACC). In this limited-size sample, the ABCC9/rs1914361 SNV was associated with HS pathology. More work is required concerning the genetic factors influencing non-Alzheimer disease pathology such as LATE-NC in diverse cohorts.

Published
2023

21. Pleobot: a modular robotic solution for metachronal swimming

Author

Santos, Sara Oliveira, Tack, Nils, Su, Yunxing, Cuenca-Jimenez, Francisco, Morales-Lopez, Oscar, Gomez-Valdez, P. Antonio, and Wilhelmus, Monica M.

Subjects
Physics - Fluid Dynamics, Physics - Biological Physics
Abstract

Metachronal locomotion is a widespread swimming mode used by aquatic swarming organisms to achieve performance and maneuverability in the intermediate Reynolds number regime. Our understanding of the mechanisms driving these abilities is limited due to the challenges of studying live organisms. Designs inspired by nature present an approach for developing small and maneuverable underwater self-propelled robots. Here, we present the design, manufacture, and validation of the \emph{Pleobot} --a unique krill-inspired robotic swimming appendage constituting the first platform to study metachronal propulsion comprehensively. Our methods combine a multi-link 3D printed mechanism with active and passive actuation of the joints to generate natural kinematics. Using force and fluid flow measurements in parallel with biological data, we show the link between the flow produced by the appendage and thrust. Further, we provide the first account of a leading-edge suction effect that contributes to lift during the power stroke. The repeatability and modularity of the \emph{Pleobot} enable the independent manipulation of particular motions and traits to test hypotheses central to understanding the relationship between form and function. Lastly, we outline future directions for the \emph{Pleobot}, including adapting morphological features. We foresee a broad appeal to a wide array of scientific disciplines, from fundamental studies in ecology, biology, and engineering, to developing new platforms for studying oceans across the solar system., Comment: 13 pages, 5 figures

Published
2023

22. Optimized time-lapse acquisition design via spectral gap ratio minimization

Author

Zhang, Yijun, Yin, Ziyi, Lopez, Oscar, Siahkoohi, Ali, Louboutin, Mathias, Kumar, Rajiv, and Herrmann, Felix J.

Subjects
Physics - Geophysics
Abstract

Modern-day reservoir management and monitoring of geological carbon storage increasingly call for costly time-lapse seismic data collection. In this letter, we show how techniques from graph theory can be used to optimize acquisition geometries for low-cost sparse 4D seismic. Based on midpoint-offset domain connectivity arguments, the proposed algorithm automatically produces sparse non-replicated time-lapse acquisition geometries that favor wavefield recovery.

Published
2023
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23. Embracing Off-the-Grid Samples

Author

López, Oscar and Yılmaz, Özgür

Subjects
Computer Science - Information Theory
Abstract

Many empirical studies suggest that samples of continuous-time signals taken at locations randomly deviated from an equispaced grid (i.e., off-the-grid) can benefit signal acquisition, e.g., undersampling and anti-aliasing. However, explicit statements of such advantages and their respective conditions are scarce in the literature. This paper provides some insight on this topic when the sampling positions are known, with grid deviations generated i.i.d. from a variety of distributions. By solving a square-root LASSO decoder with an interpolation kernel we demonstrate the capabilities of nonuniform samples for compressive sampling, an effective paradigm for undersampling and anti-aliasing. For functions in the Wiener algebra that admit a discrete $s$-sparse representation in some transform domain, we show that $\mathcal{O}(s\log N)$ random off-the-grid samples are sufficient to recover an accurate $\frac{N}{2}$-bandlimited approximation of the signal. For sparse signals (i.e., $s \ll N$), this sampling complexity is a great reduction in comparison to equispaced sampling where $\mathcal{O}(N)$ measurements are needed for the same quality of reconstruction (Nyquist-Shannon sampling theorem). We further consider noise attenuation via oversampling (relative to a desired bandwidth), a standard technique with limited theoretical understanding when the sampling positions are non-equispaced. By solving a least squares problem, we show that $\mathcal{O}(N\log N)$ i.i.d. randomly deviated samples provide an accurate $\frac{N}{2}$-bandlimited approximation of the signal with suppression of the noise energy by a factor $\sim\frac{1}{\sqrt{\log N}}$.

Published
2022

25. Design and Implementation of a Monitoring System for Ultraviolet Index, Temperature, Relative Humidity and Atmospheric Pressure

Author

Lozada Vilca, Russel Allidren, Huaman, Ciro William Taipe, Vilca, Wilson Jose Pampa, Atco, Maximo Amancio Montalvo, López, Oscar Mauricio Flores, Chumbimune, Jorge Jesus Chumbipuma, Kacprzyk, Janusz, Series Editor, Novikov, Dmitry A., Editorial Board Member, Shi, Peng, Editorial Board Member, Cao, Jinde, Editorial Board Member, Polycarpou, Marios, Editorial Board Member, Pedrycz, Witold, Editorial Board Member, Alareeni, Bahaaeddin, editor, and Elgedawy, Islam, editor

Published
2024
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27. Robust, fully-automated assessment of cerebral perivascular spaces and white matter lesions: a multicentre MRI longitudinal study of their evolution and association with risk of dementia and accelerated brain atrophy

Author

Weiner, Michael, Aisen, Paul, Petersen, Ronald, Jack, Clifford R., Jagust, William, Trojanowki, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Saykin, Andrew J., Morris, John, Shaw, Leslie M., Liu, Enchi, Montine, Tom, Thomas, Ronald G., Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Jiminez, Gus, Harvey, Danielle, Bernstein, Matthew, Fox, Nick, Thompson, Paul, Schuff, Norbert, DeCarli, Charles, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Vemuri, Prashanthi, Jones, David, Kantarci, Kejal, Ward, Chad, Koeppe, Robert A., Foster, Norm, Reiman, Eric M., Chen, Kewei, Mathis, Chet, Landau, Susan, Cairns, Nigel J., Householder, Erin, Reinwald, Lisa Taylor, Lee, Virginia, Korecka, Magdalena, Figurski, Michal, Crawford, Karen, Neu, Scott, Foroud, Tatiana M., Potkin, Steven, Shen, Li, Kelley, Faber, Kim, Sungeun, Nho, Kwangsik, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J., Molchan, Susan, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Carter, Raina, Dolen, Sara, Schneider, Lon S., Pawluczyk, Sonia, Beccera, Mauricio, Teodoro, Liberty, Spann, Bryan M., Brewer, James, Vanderswag, Helen, Fleisher, Adam, Heidebrink, Judith L., Lord, Joanne L., Mason, Sara S., Albers, Colleen S., Knopman, David, Johnson, Kris, Doody, Rachelle S., Meyer, Javier Villanueva, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S., Bell, Karen L., Ances, Beau, Morris, John C., Carroll, Maria, Leon, Sue, Mintun, Mark A., Schneider, Stacy, Oliver, Angela, Marson, Daniel, Griffith, Randall, Clark, David, Geld-macher, David, Brockington, John, Roberson, Erik, Grossman, Hillel, Mitsis, Effie, Leyla deToledo-Morrell, Shah, Raj C., Duara, Ranjan, Varon, Daniel, Greig, Maria T., Roberts, Peggy, Albert, Marilyn, Onyike, Chiadi, D’Agostino, Daniel, Kielb, Stephanie, Galvin, James E., Pogorelec, Dana M., Cerbone, Brittany, Michel, Christina A., Rusinek, Henry, de Leon, Mony J., Glodzik, Lidia, De Santi, Susan, Doraiswamy, P. Murali, Petrella, Jeffrey R., Wong, Terence Z., Arnold, Steven E., Karlawish, Jason H., Wolk, David, Smith, Charles D., Jicha, Greg, Hardy, Peter, Sinha, Partha, Oates, Elizabeth, Conrad, Gary, Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Porsteinsson, Anton P., Goldstein, Bonnie S., Martin, Kim, Makino, Kelly M., Ismail, M. Saleem, Brand, Connie, Mulnard, Ruth A., Thai, Gaby, Adams Ortiz, Catherine Mc, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Arrastia, Ramon Diaz, King, Richard, Weiner, Myron, Cook, Kristen Martin, DeVous, Michael, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Anderson, Heather S., Swerdlow, Russell H., Apostolova, Liana, Tingus, Kathleen, Woo, Ellen, Silverman, Daniel H.S., Lu, Po H., Bartzokis, George, Graff Radford, Neill R., Parfitt, Francine, Kendall, Tracy, Johnson, Heather, Farlow, Martin R., Hake, AnnMarie, Matthews, Brandy R., Herring, Scott, Hunt, Cynthia, van Dyck, Christopher H., Carson, Richard E., MacAvoy, Martha G., Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Robin Hsiung, Ging-Yuek, Feldman, Howard, Mudge, Benita, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Kerwin, Diana, Mesulam, Marek Marsel, Lipowski, Kristine, Wu, Chuang Kuo, Johnson, Nancy, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A., Johnson, Keith A., Marshall, Gad, Frey, Meghan, Yesavage, Jerome, Taylor, Joy L., Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan N., Belden, Christine M., Jacobson, Sandra A., Sirrel, Sherye A., Kowall, Neil, Killiany, Ronald, Budson, Andrew E., Norbash, Alexander, Johnson, Patricia Lynn, Obisesan, Thomas O., Wolday, Saba, Allard, Joanne, Lerner, Alan, Ogrocki, Paula, Hudson, Leon, Fletcher, Evan, Carmichael, Owen, Olichney, John, Kittur, Smita, Borrie, Michael, Lee, T.Y., Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Potkin, Steven G., Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W., Kataki, Maria, Adeli, Anahita, Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Santulli, Robert B., Kitzmiller, Tamar J., Schwartz, Eben S., Sink, Kaycee M., Williamson, Jeff D., Garg, Pradeep, Watkins, Franklin, Ott, Brian R., Querfurth, Henry, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J., Miller, Bruce L., Mintzer, Jacobo, Spicer, Kenneth, Bachman, David, Finger, Elizabeth, Pasternak, Stephen, Rachinsky, Irina, Drost, Dick, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K., Boles Ponto, Laura L., Shim, Hyungsub, Smith, Karen Elizabeth, Relkin, Norman, Chaing, Gloria, Raudin, Lisa, Smith, Amanda, Fargher, Kristin, Raj, Balebail Ashok, Barisano, Giuseppe, Iv, Michael, Choupan, Jeiran, and Hayden-Gephart, Melanie

Published
2025
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31. Proteome Network Analysis Identifies Potential Biomarkers for Brain Aging

Author

Short, Meghan I, Fohner, Alison E, Skjellegrind, Håvard K, Beiser, Alexa, Gonzales, Mitzi M, Satizabal, Claudia L, Austin, Thomas R, Longstreth, WT, Bis, Joshua C, Lopez, Oscar, Hveem, Kristian, Selbæk, Geir, Larson, Martin G, Yang, Qiong, Aparicio, Hugo J, McGrath, Emer R, Gerszten, Robert E, DeCarli, Charles S, Psaty, Bruce M, Vasan, Ramachandran S, Zare, Habil, and Seshadri, Sudha

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Prevention, Brain Disorders, Aging, Neurodegenerative, Acquired Cognitive Impairment, Dementia, Clinical Research, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), 2.1 Biological and endogenous factors, Neurological, Humans, Proteome, Proteomics, Brain, Alzheimer Disease, Biomarkers, Magnetic Resonance Imaging, Inflammation, Alzheimer's disease, biomarkers, dementia, endophenotypes, magnetic resonance imaging, proteomics, Alzheimer’s disease, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences, Biological psychology
Abstract

BackgroundAlzheimer's disease and related dementias (ADRD) involve biological processes that begin years to decades before onset of clinical symptoms. The plasma proteome can offer insight into brain aging and risk of incident dementia among cognitively healthy adults.ObjectiveTo identify biomarkers and biological pathways associated with neuroimaging measures and incident dementia in two large community-based cohorts by applying a correlation-based network analysis to the plasma proteome.MethodsWeighted co-expression network analysis of 1,305 plasma proteins identified four modules of co-expressed proteins, which were related to MRI brain volumes and risk of incident dementia over a median 20-year follow-up in Framingham Heart Study (FHS) Offspring cohort participants (n = 1,861). Analyses were replicated in the Cardiovascular Health Study (CHS) (n = 2,117, mean 6-year follow-up).ResultsTwo proteomic modules, one related to protein clearance and synaptic maintenance (M2) and a second to inflammation (M4), were associated with total brain volume in FHS (M2: p = 0.014; M4: p = 4.2×10-5). These modules were not significantly associated with hippocampal volume, white matter hyperintensities, or incident all-cause or AD dementia. Associations with TCBV did not replicate in CHS, an older cohort with a greater burden of comorbidities.ConclusionsProteome networks implicate an early role for biological pathways involving inflammation and synaptic function in preclinical brain atrophy, with implications for clinical dementia.

Published
2023

32. Identification of circulating proteins associated with general cognitive function among middle-aged and older adults

Author

Tin, Adrienne, Fohner, Alison E, Yang, Qiong, Brody, Jennifer A, Davies, Gail, Yao, Jie, Liu, Dan, Caro, Ilana, Lindbohm, Joni V, Duggan, Michael R, Meirelles, Osorio, Harris, Sarah E, Gudmundsdottir, Valborg, Taylor, Adele M, Henry, Albert, Beiser, Alexa S, Shojaie, Ali, Coors, Annabell, Fitzpatrick, Annette L, Langenberg, Claudia, Satizabal, Claudia L, Sitlani, Colleen M, Wheeler, Eleanor, Tucker-Drob, Elliot M, Bressler, Jan, Coresh, Josef, Bis, Joshua C, Candia, Julián, Jennings, Lori L, Pietzner, Maik, Lathrop, Mark, Lopez, Oscar L, Redmond, Paul, Gerszten, Robert E, Rich, Stephen S, Heckbert, Susan R, Austin, Thomas R, Hughes, Timothy M, Tanaka, Toshiko, Emilsson, Valur, Vasan, Ramachandran S, Guo, Xiuqing, Zhu, Yineng, Tzourio, Christophe, Rotter, Jerome I, Walker, Keenan A, Ferrucci, Luigi, Kivimäki, Mika, Breteler, Monique MB, Cox, Simon R, Debette, Stephanie, Mosley, Thomas H, Gudnason, Vilmundur G, Launer, Lenore J, Psaty, Bruce M, Seshadri, Sudha, and Fornage, Myriam

Subjects
Biochemistry and Cell Biology, Biological Sciences, Prevention, Acquired Cognitive Impairment, Brain Disorders, Neurosciences, Aging, Alzheimer's Disease, Behavioral and Social Science, Dementia, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), 2.1 Biological and endogenous factors, Neurological, Middle Aged, Humans, Aged, Alzheimer Disease, Cognition, Cognitive Dysfunction, Neurons, Biomarkers, Biological sciences, Biomedical and clinical sciences
Abstract

Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p

Published
2023

34. Near-Optimal Weighted Matrix Completion

Author

López, Oscar

Subjects
Computer Science - Information Theory, E.4
Abstract

Recent work in the matrix completion literature has shown that prior knowledge of a matrix's row and column spaces can be successfully incorporated into reconstruction programs to substantially benefit matrix recovery. This paper proposes a novel methodology that exploits more general forms of known matrix structure in terms of subspaces. The work derives reconstruction error bounds that are informative in practice, providing insight to previous approaches in the literature while introducing novel programs that severely reduce sampling complexity. The main result shows that a family of weighted nuclear norm minimization programs incorporating a $M_1 r$-dimensional subspace of $n\times n$ matrices (where $M_1\geq 1$ conveys structural properties of the subspace) allow accurate approximation of a rank $r$ matrix aligned with the subspace from a near-optimal number of observed entries (within a logarithmic factor of $M_1 r)$. The result is robust, where the error is proportional to measurement noise, applies to full rank matrices, and reflects degraded output when erroneous prior information is utilized. Numerical experiments are presented that validate the theoretical behavior derived for several example weighted programs., Comment: 41 pages, 2 figures

Published
2022

35. Spectral Gap-Based Seismic Survey Design

Author

López, Oscar, Kumar, Rajiv, Moldoveanu, Nick, and Herrmann, Felix

Subjects
Computer Science - Information Theory, E.4
Abstract

Seismic imaging in challenging sedimentary basins and reservoirs requires acquiring, processing, and imaging very large volumes of data (tens of terabytes). To reduce the cost of acquisition and the time from acquiring the data to producing a subsurface image, novel acquisition systems based on compressive sensing, low-rank matrix recovery, and randomized sampling have been developed and implemented. These approaches allow practitioners to achieve dense wavefield reconstruction from a substantially reduced number of field samples. However, designing acquisition surveys suited for this new sampling paradigm remains a critical and challenging role in oil, gas, and geothermal exploration. Typical random designs studied in the low-rank matrix recovery and compressive sensing literature are difficult to achieve by standard industry hardware. For practical purposes, a compromise between stochastic and realizable samples is needed. In this paper, we propose a deterministic and computationally cheap tool to alleviate randomized acquisition design, prior to survey deployment and large-scale optimization. We consider universal and deterministic matrix completion results in the context of seismology, where a bipartite graph representation of the source-receiver layout allows for the respective spectral gap to act as a quality metric for wavefield reconstruction. We provide realistic scenarios to demonstrate the utility of the spectral gap as a flexible tool that can be incorporated into existing survey design workflows for successful seismic data acquisition via low-rank and sparse signal recovery.

Published
2022
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36. RoboKrill : a metachronal drag-based swimmer robot

Author

Santos, Sara Oliveira, Cuenca-Jiménez, Francisco, Gomez-Valdez, P. Antonio, Morales-Lopez, Oscar, and Wilhelmus, Monica M.

Subjects
Computer Science - Robotics, Physics - Biological Physics
Abstract

Marine exploration is essential to understanding ocean processes and organisms. While the use of current unmanned underwater vehicles has enabled many discoveries, there are still plenty of limitations toward exploring complex environments. Bio-inspired robots are a promising solution for highly maneuverable underwater swimming at moderate speeds. Krill, especially, are efficient swimmers in the intermediate Reynolds number regime and can inform engineering solutions for ocean exploration. In this paper, we present the design, manufacture, and validation of a new krill-inspired, metachronal, drag-based robotic system. By combining active and passive actuation of the joints with 3D printed parts, our unique design recreates the swimming kinematics of Euphausia superba in a compact and reproducible robotic platform. The motion of the anterior and posterior appendage segments is achieved using servo motors and a multi-link mechanism, while the out-of-plane motion of the biramous distal segments is attained via fluid-structure interactions. Going forward, our platform will be leveraged to study metachronal, drag-based swimmers across taxa to identify unifying success mechanisms at different scales, facilitating the development of a new generation of underwater robots.

Published
2022

37. A population‐based meta‐analysis of circulating GFAP for cognition and dementia risk

Author

Gonzales, Mitzi M, Wiedner, Crystal, Wang, Chen‐Pin, Liu, Qianqian, Bis, Joshua C, Li, Zhiguang, Himali, Jayandra J, Ghosh, Saptaparni, Thomas, Emy A, Parent, Danielle M, Kautz, Tiffany F, Pase, Matthew P, Aparicio, Hugo J, Djoussé, Luc, Mukamal, Kenneth J, Psaty, Bruce M, Longstreth, William T, Mosley, Thomas H, Gudnason, Vilmundur, Mbangdadji, Djass, Lopez, Oscar L, Yaffe, Kristine, Sidney, Stephen, Bryan, R Nick, Nasrallah, Ilya M, DeCarli, Charles S, Beiser, Alexa S, Launer, Lenore J, Fornage, Myriam, Tracy, Russell P, Seshadri, Sudha, and Satizabal, Claudia L

Subjects
Clinical and Health Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, Prevention, Neurodegenerative, Brain Disorders, Alzheimer's Disease, Acquired Cognitive Impairment, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Clinical Research, Neurological, Alzheimer Disease, Antihypertensive Agents, Apolipoproteins, Cognition, Glial Fibrillary Acidic Protein, Humans, Clinical Sciences, Clinical and health psychology
Abstract

ObjectiveExpression of glial fibrillary acidic protein (GFAP), a marker of reactive astrocytosis, colocalizes with neuropathology in the brain. Blood levels of GFAP have been associated with cognitive decline and dementia status. However, further examinations at a population-based level are necessary to broaden generalizability to community settings.MethodsCirculating GFAP levels were assayed using a Simoa HD-1 analyzer in 4338 adults without prevalent dementia from four longitudinal community-based cohort studies. The associations between GFAP levels with general cognition, total brain volume, and hippocampal volume were evaluated with separate linear regression models in each cohort with adjustment for age, sex, education, race, diabetes, systolic blood pressure, antihypertensive medication, body mass index, apolipoprotein E ε4 status, site, and time between GFAP blood draw and the outcome. Associations with incident all-cause and Alzheimer's disease dementia were evaluated with adjusted Cox proportional hazard models. Meta-analysis was performed on the estimates derived from each cohort using random-effects models.ResultsMeta-analyses indicated that higher circulating GFAP associated with lower general cognition (ß = -0.09, [95% confidence interval [CI]: -0.15 to -0.03], p = 0.005), but not with total brain or hippocampal volume (p > 0.05). However, each standard deviation unit increase in log-transformed GFAP levels was significantly associated with a 2.5-fold higher risk of incident all-cause dementia (Hazard Ratio [HR]: 2.47 (95% CI: 1.52-4.01)) and Alzheimer's disease dementia (HR: 2.54 [95% CI: 1.42-4.53]) over up to 15-years of follow-up.InterpretationResults support the potential role of circulating GFAP levels for aiding dementia risk prediction and improving clinical trial stratification in community settings.

Published
2022

38. Zero-Truncated Poisson Regression for Sparse Multiway Count Data Corrupted by False Zeros

Author

López, Oscar, Dunlavy, Daniel M., and Lehoucq, Richard B.

Subjects
Statistics - Methodology, Computer Science - Mathematical Software, Mathematics - Numerical Analysis, Mathematics - Statistics Theory, Statistics - Machine Learning
Abstract

We propose a novel statistical inference methodology for multiway count data that is corrupted by false zeros that are indistinguishable from true zero counts. Our approach consists of zero-truncating the Poisson distribution to neglect all zero values. This simple truncated approach dispenses with the need to distinguish between true and false zero counts and reduces the amount of data to be processed. Inference is accomplished via tensor completion that imposes low-rank tensor structure on the Poisson parameter space. Our main result shows that an $N$-way rank-$R$ parametric tensor $\boldsymbol{\mathscr{M}}\in(0,\infty)^{I\times \cdots\times I}$ generating Poisson observations can be accurately estimated by zero-truncated Poisson regression from approximately $IR^2\log_2^2(I)$ non-zero counts under the nonnegative canonical polyadic decomposition. Our result also quantifies the error made by zero-truncating the Poisson distribution when the parameter is uniformly bounded from below. Therefore, under a low-rank multiparameter model, we propose an implementable approach guaranteed to achieve accurate regression in under-determined scenarios with substantial corruption by false zeros. Several numerical experiments are presented to explore the theoretical results., Comment: 30 pages, 5 figures

Published
2022

40. Gene-mapping study of extremes of cerebral small vessel disease reveals TRIM47 as a strong candidate

Author

Mishra, Aniket, Duplaà, Cécile, Vojinovic, Dina, Suzuki, Hideaki, Sargurupremraj, Muralidharan, Zilhão, Nuno R, Li, Shuo, Bartz, Traci M, Jian, Xueqiu, Zhao, Wei, Hofer, Edith, Wittfeld, Katharina, Harris, Sarah E, van der Auwera-Palitschka, Sandra, Luciano, Michelle, Bis, Joshua C, Adams, Hieab HH, Satizabal, Claudia L, Gottesman, Rebecca F, Gampawar, Piyush G, Bülow, Robin, Weiss, Stefan, Yu, Miao, Bastin, Mark E, Lopez, Oscar L, Vernooij, Meike W, Beiser, Alexa S, Völker, Uwe, Kacprowski, Tim, Soumare, Aicha, Smith, Jennifer A, Knopman, David S, Morris, Zoe, Zhu, Yicheng, Rotter, Jerome I, Dufouil, Carole, Hernández, Maria Valdés, Maniega, Susana Muñoz, Lathrop, Mark, Boerwinkle, Erik, Schmidt, Reinhold, Ihara, Masafumi, Mazoyer, Bernard, Yang, Qiong, Joutel, Anne, Tournier-Lasserve, Elizabeth, Launer, Lenore J, Deary, Ian J, Mosley, Thomas H, Amouyel, Philippe, DeCarli, Charles S, Psaty, Bruce M, Tzourio, Christophe, Kardia, Sharon LR, Grabe, Hans J, Teumer, Alexander, van Duijn, Cornelia M, Schmidt, Helena, Wardlaw, Joanna M, Ikram, M Arfan, Fornage, Myriam, Gudnason, Vilmundur, Seshadri, Sudha, Matthews, Paul M, Longstreth, William T, Couffinhal, Thierry, and Debette, Stephanie

Subjects
Epidemiology, Health Sciences, Neurosciences, Cerebrovascular, Neurodegenerative, Brain Disorders, Human Genome, Aging, Alzheimer's Disease Related Dementias (ADRD), Stroke, Vascular Cognitive Impairment/Dementia, Dementia, Acquired Cognitive Impairment, Minority Health, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Clinical Research, Genetics, 2.1 Biological and endogenous factors, Cardiovascular, Neurological, Animals, Brain Ischemia, Cerebral Small Vessel Diseases, Endothelial Cells, Genome-Wide Association Study, Mice, cerebral small vessel disease, endothelial cells, GWAS, TRIM47, whole-exome association study, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

Cerebral small vessel disease is a leading cause of stroke and a major contributor to cognitive decline and dementia, but our understanding of specific genes underlying the cause of sporadic cerebral small vessel disease is limited. We report a genome-wide association study and a whole-exome association study on a composite extreme phenotype of cerebral small vessel disease derived from its most common MRI features: white matter hyperintensities and lacunes. Seventeen population-based cohorts of older persons with MRI measurements and genome-wide genotyping (n = 41 326), whole-exome sequencing (n = 15 965), or exome chip (n = 5249) data contributed 13 776 and 7079 extreme small vessel disease samples for the genome-wide association study and whole-exome association study, respectively. The genome-wide association study identified significant association of common variants in 11 loci with extreme small vessel disease, of which the chr12q24.11 locus was not previously reported to be associated with any MRI marker of cerebral small vessel disease. The whole-exome association study identified significant associations of extreme small vessel disease with common variants in the 5' UTR region of EFEMP1 (chr2p16.1) and one probably damaging common missense variant in TRIM47 (chr17q25.1). Mendelian randomization supports the causal association of extensive small vessel disease severity with increased risk of stroke and Alzheimer's disease. Combined evidence from summary-based Mendelian randomization studies and profiling of human loss-of-function allele carriers showed an inverse relation between TRIM47 expression in the brain and blood vessels and extensive small vessel disease severity. We observed significant enrichment of Trim47 in isolated brain vessel preparations compared to total brain fraction in mice, in line with the literature showing Trim47 enrichment in brain endothelial cells at single cell level. Functional evaluation of TRIM47 by small interfering RNAs-mediated knockdown in human brain endothelial cells showed increased endothelial permeability, an important hallmark of cerebral small vessel disease pathology. Overall, our comprehensive gene-mapping study and preliminary functional evaluation suggests a putative role of TRIM47 in the pathophysiology of cerebral small vessel disease, making it an important candidate for extensive in vivo explorations and future translational work.

Published
2022

42. APOEε4 potentiates amyloid β effects on longitudinal tau pathology

Author

Ferrari-Souza, João Pedro, Bellaver, Bruna, Ferreira, Pâmela C. L., Benedet, Andréa L., Povala, Guilherme, Lussier, Firoza Z., Leffa, Douglas T., Therriault, Joseph, Tissot, Cécile, Soares, Carolina, Wang, Yi-Ting, Chamoun, Mira, Servaes, Stijn, Macedo, Arthur C., Vermeiren, Marie, Bezgin, Gleb, Kang, Min Su, Stevenson, Jenna, Rahmouni, Nesrine, Pallen, Vanessa, Poltronetti, Nina Margherita, Cohen, Ann, Lopez, Oscar L., Klunk, William E., Soucy, Jean-Paul, Gauthier, Serge, Souza, Diogo O., Triana-Baltzer, Gallen, Saad, Ziad S., Kolb, Hartmuth C., Karikari, Thomas K., Villemagne, Victor L., Tudorascu, Dana L., Ashton, Nicholas J., Zetterberg, Henrik, Blennow, Kaj, Zimmer, Eduardo R., Rosa-Neto, Pedro, and Pascoal, Tharick A.

Published
2023
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47. The link between Bitcoin and Google Trends attention

Author

Aslanidis, Nektarios, Bariviera, Aurelio F., and López, Óscar G.

Subjects
Quantitative Finance - Statistical Finance
Abstract

This paper shows that Bitcoin is not correlated to a general uncertainty index as measured by the Google Trends data of Castelnuovo and Tran (2017). Instead, Bitcoin is linked to a Google Trends attention measure specific for the cryptocurrency market. First, we find a bidirectional relationship between Google Trends attention and Bitcoin returns up to six days. Second, information flows from Bitcoin volatility to Google Trends attention seem to be larger than information flows in the other direction. These relations hold across different sub-periods and different compositions of the proposed Google Trends Cryptocurrency index., Comment: 9 pages, 5 figures

Published
2021

48. Blood Pressure and Later-Life Cognition in Hispanic and White Adults (BP-COG): A Pooled Cohort Analysis of ARIC, CARDIA, CHS, FOS, MESA, and NOMAS.

Author

Levine, Deborah A, Gross, Alden L, Briceño, Emily M, Tilton, Nicholas, Whitney, Rachael, Han, Dehua, Giordani, Bruno J, Sussman, Jeremy B, Hayward, Rodney A, Burke, James F, Elkind, Mitchell SV, Moran, Andrew E, Tom, Sarah, Gottesman, Rebecca F, Gaskin, Darrell J, Sidney, Stephen, Yaffe, Kristine, Sacco, Ralph L, Heckbert, Susan R, Hughes, Timothy M, Lopez, Oscar L, Allen, Norrina Bai, and Galecki, Andrzej T

Subjects
Biological Psychology, Psychology, Aging, Brain Disorders, Acquired Cognitive Impairment, Dementia, Behavioral and Social Science, Neurosciences, Clinical Research, Cardiovascular, Aged, Blood Pressure, Cognition, Cohort Studies, Female, Hispanic or Latino, Humans, Male, Risk Factors, White People, Blood pressure, cognition, dementia, ethnic groups, Hispanic Americans, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences, Biological psychology
Abstract

BackgroundEthnic differences in cognitive decline have been reported. Whether they can be explained by differences in systolic blood pressure (SBP) is uncertain.ObjectiveDetermine whether cumulative mean SBP levels explain differences in cognitive decline between Hispanic and White individuals.MethodsPooled cohort study of individual participant data from six cohorts (1971-2017). The present study reports results on SBP and cognition among Hispanic and White individuals. Outcomes were changes in global cognition (GC) (primary), executive function (EF) (secondary), and memory standardized as t-scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1 SD difference in cognition. Median follow-up was 7.7 (Q1-Q3, 5.2-20.1) years.ResultsWe included 24,570 participants free of stroke and dementia: 2,475 Hispanic individuals (median age, cumulative mean SBP at first cognitive assessment, 67 years, 132.5 mmHg; 40.8% men) and 22,095 White individuals (60 years,134 mmHg; 47.3% men). Hispanic individuals had slower declines in GC, EF, and memory than White individuals when all six cohorts were examined. Two cohorts recruited Hispanic individuals by design. In a sensitivity analysis, Hispanic individuals in these cohorts had faster decline in GC, similar decline in EF, and slower decline in memory than White individuals. Higher time-varying cumulative mean SBP was associated with faster declines in GC, EF, and memory in all analyses. After adjusting for time-varying cumulative mean SBP, differences in cognitive slopes between Hispanic and White individuals did not change.ConclusionWe found no evidence that cumulative mean SBP differences explained differences in cognitive decline between Hispanic and White individuals.

Published
2022

49. Associations of Pulmonary Function with MRI Brain Volumes: A Coordinated Multi-Study Analysis

Author

Frenzel, Stefan, Bis, Joshua C, Gudmundsson, Elias F, O’Donnell, Adrienne, Simino, Jeannette, Yaqub, Amber, Bartz, Traci M, Brusselle, Guy GO, Bülow, Robin, DeCarli, Charles S, Ewert, Ralf, Gharib, Sina A, Ghosh, Saptaparni, Gireud-Goss, Monica, Gottesman, Rebecca F, Ikram, M Arfan, Knopman, David S, Launer, Lenore J, London, Stephanie J, Longstreth, WT, Lopez, Oscar L, van Lent, Debora Melo, O’Connor, George, Satizabal, Claudia L, Shrestha, Srishti, Sigurdsson, Sigurdur, Stubbe, Beate, Talluri, Rajesh, Vasan, Ramachandran S, Vernooij, Meike W, Völzke, Henry, Wiggins, Kerri L, Yu, Bing, Beiser, Alexa S, Gudnason, Vilmundur, Mosley, Thomas, Psaty, Bruce M, Wolters, Frank J, Grabe, Hans J, and Seshadri, Sudha

Subjects
Brain Disorders, Lung, Neurosciences, Clinical Research, Aging, Humans, Aged, Forced Expiratory Volume, Cross-Sectional Studies, Magnetic Resonance Imaging, Brain, Dementia, epidemiology, magnetic resonance imaging, respiratory function tests, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

BackgroundPrevious studies suggest poor pulmonary function is associated with increased burden of cerebral white matter hyperintensities and brain atrophy among elderly individuals, but the results are inconsistent.ObjectiveTo study the cross-sectional associations of pulmonary function with structural brain variables.MethodsData from six large community-based samples (N = 11,091) were analyzed. Spirometric measurements were standardized with respect to age, sex, height, and ethnicity using reference equations of the Global Lung Function Initiative. Associations of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and their ratio FEV1/FVC with brain volume, gray matter volume, hippocampal volume, and volume of white matter hyperintensities were investigated using multivariable linear regressions for each study separately and then combined using random-effect meta-analyses.ResultsFEV1 and FVC were positively associated with brain volume, gray matter volume, and hippocampal volume, and negatively associated with white matter hyperintensities volume after multiple testing correction, with little heterogeneity present between the studies. For instance, an increase of FVC by one unit was associated with 3.5 ml higher brain volume (95% CI: [2.2, 4.9]). In contrast, results for FEV1/FVC were more heterogeneous across studies, with significant positive associations with brain volume, gray matter volume, and hippocampal volume, but not white matter hyperintensities volume. Associations of brain variables with both FEV1 and FVC were consistently stronger than with FEV1/FVC, specifically with brain volume and white matter hyperintensities volume.ConclusionIn cross-sectional analyses, worse pulmonary function is associated with smaller brain volumes and higher white matter hyperintensities burden.

Published
2022

50. Cardiovascular damage phenotypes and all-cause and CVD mortality in older adults

Author

Miller, Lindsay M, Wu, Chenkai, Hirsch, Calvin H, Lopez, Oscar L, Cushman, Mary, and Odden, Michelle C

Subjects
Epidemiology, Biomedical and Clinical Sciences, Clinical Sciences, Health Sciences, Heart Disease, Prevention, Aging, Clinical Research, Cardiovascular, Genetics, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Aged, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Humans, Phenotype, Risk Factors, Risk factors, Cardiovascular disease, Latent Class Analysis, AAI, ankle arm index, ADL, Activities of Daily Living, AIC, Akaike Information Criterion, APOE, Apolipoprotein e4, BIC, Bayesian Information Criterion, CHS, Cardiovascular Health Study, CRP, C-reactive protein, ECG, major echocardiogram abnormalities, GOF, Goodness of Fit, Gal3, galectin-3, HR, Hazard Ratio, IL-6, interleukin-6, IMT, internal intima-media thickness, LCA, Latent Class Analysis, LDLcholesterol, Low-density Lipoprotein Cholesterol, NTproBNP, N-terminal probrain natriuretic peptide, Risk factors, Cardiovascular disease, Latent Class Analysis. Abbreviations: CVD, Cardiovascular Disease, SCVD, Subclinical Cardiovascular Disease, WMG, white matter grade, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

PurposeThe association between CVD risk factors and mortality is well established, however, current tools for addressing subgroups have focused on the overall burden of disease. The identification of risky combinations of characteristics may lead to a better understanding of physiologic pathways that underlie morbidity and mortality in older adults.MethodsParticipants included 5067 older adults from the Cardiovascular Health Study, followed for up to 6 years. Using latent class analysis (LCA), we created CV damage phenotypes based on probabilities of abnormal brain infarctions, major echocardiogram abnormalities, N-terminal probrain natriuretic peptide, troponin T, interleukin-6, c reactive-protein, galectin-3, cystatin C. We assigned class descriptions based on the probability of having an abnormality among risk factors, such that a healthy phenotype would have low probabilities in all risk factors. Participants were assigned to phenotypes based on the maximum probability of membership. We used Cox-proportional hazards regression to evaluate the association between the categorical CV damage phenotype and all-cause and CVD-mortality.ResultsThe analysis yielded 5 CV damage phenotypes consistent with the following descriptions: healthy (59%), cardio-renal (11%), cardiac (15%), multisystem morbidity (6%), and inflammatory (9%). All four phenotypes were statistically associated with a greater risk of all-cause mortality when compared with the healthy phenotype. The multisystem morbidity phenotype had the greatest risk of all-cause death (HR: 4.02; 95% CI: 3.44, 4.70), and CVD-mortality (HR: 4.90, 95% CI: 3.95, 6.06).ConclusionsFive CV damage phenotypes emerged from CVD risk factor measures. CV damage across multiple systems confers a greater mortality risk compared to damage in any single domain.

Published
2021

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