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2. A Novel Causal Mediation Analysis Approach for Zero-Inflated Mediators

Author

Jiang, Meilin, Lee, Seonjoo, O'Malley, James, Stern, Yaakov, and Li, Zhigang

Subjects
Statistics - Applications, Mathematics - Statistics Theory
Abstract

Mediation analyses play important roles in making causal inference in biomedical research to examine causal pathways that may be mediated by one or more intermediate variables (i.e., mediators). Although mediation frameworks have been well established such as counterfactual-outcomes (i.e., potential-outcomes) models and traditional linear mediation models, little effort has been devoted to dealing with mediators with zero-inflated structures due to challenges associated with excessive zeros. We develop a novel mediation modeling approach to address zero-inflated mediators containing true zeros and false zeros. The new approach can decompose the total mediation effect into two components induced by zero-inflated structures: the first component is attributable to the change in the mediator on its numerical scale which is a sum of two causal pathways and the second component is attributable only to its binary change from zero to a non-zero status. An extensive simulation study is conducted to assess the performance and it shows that the proposed approach outperforms existing standard causal mediation analysis approaches. We also showcase the application of the proposed approach to a real study in comparison with a standard causal mediation analysis approach., Comment: Corresponding: zhigang.li@ufl.edu

Published
2023

3. The (in)visible Brazilians: A perspective review on the need for brain health and dementia research with Brazilian immigrants in the United States.

Author

Simon, Sharon, Brucki, Sonia, Fonseca, Luciana, Becker, Jacqueline, Cappi, Carolina, Marques, Andrea, Heyn, Patricia, Gonçalves, Priscila, Martins, Silvia, Busatto, Geraldo, Suemoto, Claudia, Nitrini, Ricardo, Caramelli, Paulo, Yassuda, Monica, Miotto, Eliane, Arce Renteria, Miguel, Alegria, Margarita, Stern, Yaakov, Rivera-Mindt, Monica, Bertola, Laiss, and Grinberg, Lea

Subjects
Alzheimers disease, Brazilian immigrants, Latinx, aging, dementia, health disparities, health equity, mental health, minority groups
Abstract

INTRODUCTION: The Brazilian population in the United States (U.S.), a Latinx subgroup, is rapidly growing and aging but remains underrepresented in U.S. health research. In addition to group-specific genetic and environmental risks, Brazilian immigrants and their offspring in the U.S. likely have cumulative risks for health inequities.It is estimated that 71% of Brazilian immigrants in the U.S. are undocumented, which may limit healthcare access/utilization. Furthermore, mental health is reported as a health priority by Brazilian immigrants in the U.S., and there is a lack of research on Alzheimers disease and related dementia (AD/ADRD) in this population. METHODS: We reviewed the scientific literature using traditional (e.g., PubMed) sources and databases generated by U.S. and Brazilian governments, as well as international organizations, and press articles. RESULTS: This perspective review lists recommendations for researchers, health providers, and policymakers to promote greater inclusion of U.S. Brazilian populations in health research and care. The review identifies research areas in need of attention to address health inequities and promote mental/brain health in Brazilian immigrants and their offspring living in the U.S. These research areas are: 1) epidemiological studies to map the prevalence and incidence of mental/brain health conditions; 2) research on aging and AD/ADRD risk factors among Brazilian populations in the U.S.; and 3) the need for greater representation of U.S-residing Brazilian population in other relevant research areas involving genetics, neuropathology, and clinical trials. CONCLUSIONS: The recommendation and research efforts proposed should help to pave the way for the development of community-engagement research and to promote mental/brain health education, improvement of mental/brain health and AD/ADRD services, and the development of culturally-informed intervention to the U.S.-residing Brazilian communities. HIGHLIGHTS: The Brazilian population in the United States is growing but is underrepresented in U.S. health research.Approximately 71% of Brazilian immigrants in the United States are undocumented, with an increased risk for health inequities.Mental health is reported as a central health priority by Brazilian immigrants in the United States.There is a lack of research on Alzheimers disease and other dementias (ADRD) in Brazilian immigrants in the United States.Epidemiological research is needed to map the prevalence/incidence of mental health conditions and ADRD risk factors among Brazilian immigrants in the United States.

Published
2023

4. A data‐driven examination of apathy and depressive symptoms in dementia with independent replication

Author

Da Silva, Miguel Vasconcelos, Melendez‐Torres, Gerardo Javier, Ismail, Zahinoor, Testad, Ingelin, Ballard, Clive, Creese, Byron, 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, Van der Swag, 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, and Oliver, Angela

Subjects
Clinical and Health Psychology, Biomedical and Clinical Sciences, Psychology, Brain Disorders, Mental Health, Depression, Mental Illness, Mental health, Alzheimer's Disease Neuroimaging Initiative, apathy, dementia, depression, latent class analysis, Genetics, Neurosciences, Biological psychology
Abstract

Apathy is one of the most common neuropsychiatric symptoms (NPS) and is associated with poor clinical outcomes. Research that helps define the apathy phenotype is urgently needed, particularly for clinical and biomarker studies. We used latent class analysis (LCA) with two independent cohorts to understand how apathy and depression symptoms co-occur statistically. We further explored the relationship between latent class membership, demographics, and the presence of other NPS. The LCA identified a four-class solution (no symptoms, apathy, depression, and combined apathy/depression), reproducible over both cohorts, providing robust support for an apathy syndrome distinct from depression and confirming that an apathy/depression syndrome exists, supported by the model fit test with the four-class solution scores evidencing better fitting (Bayesian information criterion adjusted and entropy R 2). Using a data-driven method, we show distinct and statistically meaningful co-occurrence of apathy and depressive symptoms. There was evidence that these classes have different clinical associations, which may help inform diagnostic categories for research studies and clinical practice.HighlightsWe found four classes: no symptoms, apathy, depression and apathy/depression.Apathy conferred a higher probability for agitation.Apathy diagnostic criteria should include accompanying neuropsychiatric symptoms.

Published
2023

7. The Caenorhabditis elegans protein SOC-3 permits an alternative mode of signal transduction by the EGL-15 FGF receptor

Author

Rodriguez Torres, Claudia S., Wicker, Nicole B., Puccini de Castro, Victória, Stefinko, Mariya, Bennett, Daniel C., Bernhardt, Brooke, Garcia Montes de Oca, Melissa, Jallow, Sainabou, Flitcroft, Katelyn, Palalay, Jessica-Jae S., Payán Parra, Omar A., Stern, Yaakov E., Koelle, Michael R., Voisine, Cindy, Woods, Ian G., Lo, Te-Wen, Stern, Michael J., and de la Cova, Claire C.

Published
2024
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18. Spatial Registration Evaluation of [18F]-MK6240 PET

Author

Zou, James, Johnson, Aubrey, France, Jeanelle, Bharadwaj, Srinidhi, Tomljanovic, Zeljko, Stern, Yaakov, Brickman, Adam M., Devanand, Devangere P., Luchsinger, Jose A., Kreisl, William C., and Provenzano, Frank A.

Subjects
Quantitative Biology - Quantitative Methods, Electrical Engineering and Systems Science - Image and Video Processing
Abstract

Image registration is an important preprocessing step in neuroimaging which allows for the matching of anatomical and functional information between modalities and subjects. This can be challenging if there are gross differences in image geometry or in signal intensity, such as in the case of some molecular PET radioligands, where control subjects display relative lack of signal relative to noise within intracranial regions, and may have off target binding that may be confused as other regions, and may vary depending on subject. The use of intermediary images or volumes have been shown to aide registration in such cases. To account for this phenomena within our own longitudinal aging cohort, we generated a population specific MRI and PET template from a broad distribution of 30 amyloid negative subjects. We then registered the PET image of each of these subjects, as well as a holdout set of thirty 'template-naive' subjects to their corresponding MRI images using the template image as an intermediate using three different sets of registration parameters and procedures. To evaluate the performance of both conventional registration and our method, we compared these to the registration of the attenuation CT (acquired at time of PET acquisition) to MRI as the reference. We then used our template to directly derive SUVR values without the use of MRI. We found that conventional registration was comparable to an existing CT based standard, and there was no significant difference in errors collectively amongst all methods tested. In addition, there were no significant differences between existing and MR-less tau PET quantification methods. We conclude that a template-based method is a feasible alternative to, or salvage for, direct registration and MR-less quantification; and, may be preferred in cases where there is doubt about the similarity between two image modalities., Comment: 19 pages, 8 Figures, 4 Tables

Published
2020

19. Clinical diagnosis of Alzheimer's disease: recommendations of the International Working Group

Author

Dubois, Bruno, Villain, Nicolas, Frisoni, Giovanni B, Rabinovici, Gil D, Sabbagh, Marwan, Cappa, Stefano, Bejanin, Alexandre, Bombois, Stéphanie, Epelbaum, Stéphane, Teichmann, Marc, Habert, Marie-Odile, Nordberg, Agneta, Blennow, Kaj, Galasko, Douglas, Stern, Yaakov, Rowe, Christopher C, Salloway, Stephen, Schneider, Lon S, Cummings, Jeffrey L, and Feldman, Howard H

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Dementia, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Aging, Brain Disorders, Neurodegenerative, Clinical Research, Prevention, 4.1 Discovery and preclinical testing of markers and technologies, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Neurological, Good Health and Well Being, Alzheimer Disease, Amyloid beta-Peptides, Biomarkers, Cognitive Dysfunction, Disease Progression, Humans, Phenotype, tau Proteins, Neurology & Neurosurgery, Clinical sciences
Abstract

In 2018, the US National Institute on Aging and the Alzheimer's Association proposed a purely biological definition of Alzheimer's disease that relies on biomarkers. Although the intended use of this framework was for research purposes, it has engendered debate and challenges regarding its use in everyday clinical practice. For instance, cognitively unimpaired individuals can have biomarker evidence of both amyloid β and tau pathology but will often not develop clinical manifestations in their lifetime. Furthermore, a positive Alzheimer's disease pattern of biomarkers can be observed in other brain diseases in which Alzheimer's disease pathology is present as a comorbidity. In this Personal View, the International Working Group presents what we consider to be the current limitations of biomarkers in the diagnosis of Alzheimer's disease and, on the basis of this evidence, we propose recommendations for how biomarkers should and should not be used for diagnosing Alzheimer's disease in a clinical setting. We recommend that Alzheimer's disease diagnosis be restricted to people who have positive biomarkers together with specific Alzheimer's disease phenotypes, whereas biomarker-positive cognitively unimpaired individuals should be considered only at-risk for progression to Alzheimer's disease.

Published
2021

20. Circular-SWAT for deep learning based diagnostic classification of Alzheimer's disease: application to metabolome data

Author

Kaddurah-Daouk, Rima, Kueider-Paisley, Alexandra, Doraiswamy, P. Murali, Blach, Colette, Moseley, Arthur, Thompson, Will, St John-Williams, Lisa, Mahmoudiandehkhordi, Siamak, Tenenbaum, Jessica, Welsh-Balmer, Kathleen, Plassman, Brenda, Saykin, Andrew J., Nho, Kwangsik, Risacher, Shannon L., Kastenmüller, Gabi, Arnold, Matthias, Han, Xianlin, Baillie, Rebecca, Knight, Rob, Dorrestein, Pieter, Brewer, James, Mayer, Emeran, Labus, Jennifer, Baldi, Pierre, Gupta, Arpana, Fiehn, Oliver, Barupal, Dinesh, Meikle, Peter, Mazmanian, Sarkis, Rader, Dan, Kling, Mitchel, Shaw, Leslie, Trojanowski, John, van Duijin, Cornelia, Nevado-Holgado, Alejo, Bennett, David, Krishnan, Ranga, Keshavarzian, Ali, Vogt, Robin, Ikram, Arfan, Hankemeier, Thomas, Thiele, Ines, Price, Nathan, Funk, Cory, Baloni, Priyanka, Jia, Wei, Wishart, David, Brinton, Roberta, Chang, Rui, Farrer, Lindsay, Au, Rhoda, Qiu, Wendy, Würtz, Peter, Koal, Therese, Mangravite, Lara, Krumsiek, Jan, Suhre, Karsten, Newman, John, Moreno, Herman, Foroud, Tatania, Sacks, Frank, Jansson, Janet, Weiner, Michael W., Aisen, Paul, Petersen, Ronald, Jack, Clifford R., Jr., Jagust, William, Trojanowki, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Morris, John C., Perrin, Richard J., Shaw, Leslie M., Khachaturian, Zaven, Carrillo, Maria, Potter, William, Barnes, Lisa, Bernard, Marie, Gonzalez, Hector, Ho, Carole, Hsiao, John K., Jackson, Jonathan, Masliah, Eliezer, Masterman, Donna, Okonkwo, Ozioma, Perrin, Richard, Ryan, Laurie, Silverberg, Nina, Fleisher, Adam, Sacrey, Diana Truran, Fockler, Juliet, Conti, Cat, Veitch, Dallas, Neuhaus, John, Jin, Chengshi, Nosheny, Rachel, Ashford, Miriam, Flenniken, Derek, Kormos, Adrienne, Montine, Tom, Rafii, Michael, Raman, Rema, Jimenez, Gustavo, Donohue, Michael, Gessert, Devon, Salazar, Jennifer, Zimmerman, Caileigh, Cabrera, Yuliana, Walter, Sarah, Miller, Garrett, Coker, Godfrey, Clanton, Taylor, Hergesheimer, Lindsey, Smith, Stephanie, Adegoke, Olusegun, Mahboubi, Payam, Moore, Shelley, Pizzola, Jeremy, Shaffer, Elizabeth, Sloan, Brittany, Harvey, Danielle, Forghanian-Arani, Arvin, Borowski, Bret, Ward, Chad, Schwarz, Christopher, Jones, David, Gunter, Jeff, Kantarci, Kejal, Senjem, Matthew, Vemuri, Prashanthi, Reid, Robert, Fox, Nick C., Malone, Ian, Thompson, Paul, Thomopoulos, Sophia I., Nir, Talia M., Jahanshad, Neda, DeCarli, Charles, Knaack, Alexander, Fletcher, Evan, Tosun-Turgut, Duygu, Chen, Stephanie Rossi, Choe, Mark, Crawford, Karen, Yushkevich, Paul A., Das, Sandhitsu, Koeppe, Robert A., Reiman, Eric M., Chen, Kewei, Mathis, Chet, Landau, Susan, Cairns, Nigel J., Householder, Erin, Franklin, Erin, Bernhardt, Haley, Taylor-Reinwald, Lisa, Korecka, Magdalena, Figurski, Michal, Neu, Scott, Apostolova, Liana G., Shen, Li, Foroud, Tatiana M., Nudelman, Kelly, Faber, Kelley, Wilmes, Kristi, Thal, Leon, Silbert, Lisa C., Lind, Betty, Crissey, Rachel, Kaye, Jeffrey A., Carter, Raina, Dolen, Sara, Quinn, Joseph, Schneider, Lon S., Pawluczyk, Sonia, Becerra, Mauricio, Teodoro, Liberty, Dagerman, Karen, Spann, Bryan M., Vanderswag, Helen, Ziolkowski, Jaimie, Heidebrink, Judith L., Zbizek-Nulph, Lisa, Lord, Joanne L., Mason, Sara S., Albers, Colleen S., Knopman, David, Johnson, Kris, Villanueva-Meyer, Javier, Pavlik, Valory, Pacini, Nathaniel, Lamb, Ashley, Kass, Joseph S., Doody, Rachelle S., Shibley, Victoria, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S., Mintz, Akiva, Ances, Beau, Winkfield, David, Carroll, Maria, Stobbs-Cucchi, Georgia, Oliver, Angela, Creech, Mary L., Mintun, Mark A., Schneider, Stacy, Geldmacher, David, Love, Marissa Natelson, Griffith, Randall, Clark, David, Brockington, John, Marson, Daniel, Grossman, Hillel, Goldstein, Martin A., Greenberg, Jonathan, Mitsis, Effie, Shah, Raj C., Lamar, Melissa, Samuels, Patricia, Duara, Ranjan, Greig-Custo, Maria T., Rodriguez, Rosemarie, Albert, Marilyn, Onyike, Chiadi, Farrington, Leonie, Rudow, Scott, Brichko, Rottislav, Kielb, Stephanie, Smith, Amanda, Raj, Balebail Ashok, Fargher, Kristin, Sadowski, Martin, Wisniewski, Thomas, Shulman, Melanie, Faustin, Arline, Rao, Julia, Castro, Karen M., Ulysse, Anaztasia, Chen, Shannon, Sheikh, Mohammed O., Singleton-Garvin, Jamika, Petrella, JeffreyR., James, Olga, Wong, Terence Z., Borges-Neto, Salvador, Karlawish, Jason H., Wolk, David A., Vaishnavi, Sanjeev, Clark, Christopher M., Arnold, Steven E., Smith, Charles D., Jicha, Gregory A., Raslau, Flavius D., Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Porsteinsson, Anton P., Martin, Kim, Kowalski, Nancy, Keltz, Melanie, Goldstein, Bonnie S., Makino, Kelly M., Ismail, M. Saleem, Brand, Connie, Thai, Gaby, Pierce, Aimee, Yanez, Beatriz, Sosa, Elizabeth, Witbracht, Megan, Kelley, Brendan, Nguyen, Trung, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Levey, Allan I., Lah, James J., Hajjar, Ihab, Cellar, Janet S., Burns, Jeffrey M., Swerdlow, Russell H., Brooks, William M., Silverman, Daniel H.S., Kremen, Sarah, Apostolova, Liana, Tingus, Kathleen, Lu, Po H., Bartzokis, George, Woo, Ellen, Teng, Edmond, Graff-Radford, Neill R., Parfitt, Francine, Poki-Walker, Kim, Farlow, Martin R., Hake, Ann Marie, Matthews, Brandy R., Brosch, Jared R., Herring, Scott, van, Christopher H., Mecca, Adam P., Good, Susan P., MacAvoy, Martha G., Carson, Richard E., Varma, Pradeep, Chertkow, Howard, Vaitekunis, Susan, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Heyn, Chris (Chinthaka), Robin Hsiung, Ging-Yuek, Kim, Ellen, Mudge, Benita, Sossi, Vesna, Feldman, Howard, Assaly, Michele, Finger, Elizabeth, Pasternak, Stephen, Rachinsky, Irina, Kertesz, Andrew, Drost, Dick, Rogers, John, Grant, Ian, Muse, Brittanie, Rogalski, Emily, Robson, Jordan, Mesulam, M.-Marsel, Kerwin, Diana, Wu, Chuang-Kuo, Johnson, Nancy, Lipowski, Kristine, Weintraub, Sandra, Bonakdarpour, Borna, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Rosen, Howard J., Miller, Bruce L., Perry, David, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, MCCann, Kelly, Poe, Jessica, Sperling, Reisa A., Johnson, Keith A., Marshall, Gad A., Yesavage, Jerome, Taylor, Joy L., Chao, Steven, Coleman, Jaila, White, Jessica D., Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Belden, Christine M., Atri, Alireza, Clark, Kelly A., Zamrini, Edward, Sabbagh, Marwan, Killiany, Ronald, Stern, Robert, Mez, Jesse, Kowall, Neil, Budson, Andrew E., Obisesan, Thomas O., Ntekim, Oyonumo E., Wolday, Saba, Khan, Javed I., Nwulia, Evaristus, Nadarajah, Sheeba, Lerner, Alan, Ogrocki, Paula, Tatsuoka, Curtis, Fatica, Parianne, Maillard, Pauline, Olichney, John, Carmichael, Owen, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Borrie, Michael, Lee, T.-Y., Bartha, Dr Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Perrin, Allison, Burke, Anna, Scharre, Douglas W., Kataki, Maria, Tarawneh, Rawan, Hart, David, Zimmerman, Earl A., Celmins, Dzintra, Miller, Delwyn D., BolesPonto, Laura L., Smith, Karen Ekstam, Koleva, Hristina, Shim, Hyungsub, Nam, Ki Won, Schultz, Susan K., Williamson, Jeff D., Craft, Suzanne, Cleveland, Jo, Yang, Mia, Sink, Kaycee M., Ott, Brian R., Drake, Jonathan, Tremont, Geoffrey, Daiello, Lori A., Drake, Jonathan D., Ritter, Aaron, Bernick, Charles, Munic, Donna, O'Connelll, Abigail, Mintzer, Jacobo, Wiliams, Arthur, Masdeu, Joseph, Shi, Jiong, Garcia, Angelica, Newhouse, Paul, Potkin, Steven, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Kittur, Smita, Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Flashman, Laura A., Seltzer, Marc, Hynes, Mary L., Santulli, Robert B., Relkin, Norman, Chiang, Gloria, Lee, Athena, Lin, Michael, Ravdin, Lisa, Petersen, Ron, Neylan, Thomas, Grafman, Jordan, Danowski, Sarah, Nguyen-Barrera, Catherine, Hayes, Jacqueline, Finley, Shannon, Bernstein, Matthew, Senjem, Matt, Foster, Norm, Kim, Sungeun, Sood, Ajay, Blanchard, Kimberly S., Fleischman, Debra, Arfanakis, Konstantinos, Varon, Daniel, Greig, Maria T., Petrella, Jeffrey R., Goldstein, Bonnie, Martin, Kimberly S., Reist, Christopher, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Rosen, Howard, Marshall, Gad, Peskind, Elaine R., Petrie, Eric C., Li, Gail, Mackin, Scott, Jimenez-Maggiora, Gustavo, Drake, Erin, Donohue, Mike, Nelson, Craig, Bickford, David, Butters, Meryl, Zmuda, Michelle, Reyes, Denise, Faber, Kelley M., Nudelman, Kelly N., Au, Yiu Ho, Scherer, Kelly, Catalinotto, Daniel, Stark, Samuel, Ong, Elise, Fernandez, Dariella, Jo, Taeho, Kim, Junpyo, Bice, Paula, Huynh, Kevin, Wang, Tingting, Meikle, Peter J., and Giles, Corey

Published
2023
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21. Trajectories of occupational physical activity and risk of later-life mild cognitive impairment and dementia: the HUNT4 70+ study

Author

Zotcheva, Ekaterina, Bratsberg, Bernt, Strand, Bjørn Heine, Jugessur, Astanand, Engdahl, Bo Lars, Bowen, Catherine, Selbæk, Geir, Kohler, Hans-Peter, Harris, Jennifer R., Weiss, Jordan, Tom, Sarah E., Krokstad, Steinar, Mekonnen, Teferi, Edwin, Trine Holt, Stern, Yaakov, Håberg, Asta Kristine, and Skirbekk, Vegard

Published
2023
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24. Race/Ethnic Disparities in Mild Cognitive Impairment and Dementia: The Northern Manhattan Study

Author

Wright, Clinton B, DeRosa, Janet T, Moon, Michelle P, Strobino, Kevin, DeCarli, Charles, Cheung, Ying Kuen, Assuras, Stephanie, Levin, Bonnie, Stern, Yaakov, Sun, Xiaoyan, Rundek, Tatjana, Elkind, Mitchell SV, and Sacco, Ralph L

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Alzheimer's Disease, Vascular Cognitive Impairment/Dementia, Aging, Acquired Cognitive Impairment, Prevention, Clinical Research, Neurodegenerative, Behavioral and Social Science, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Dementia, Neurological, Mental health, Aged, Aged, 80 and over, Cognitive Dysfunction, Cohort Studies, Cross-Sectional Studies, Ethnicity, Female, Humans, Male, Middle Aged, New York City, Prevalence, African American, cohort studies, dementia, Hispanic American, mild cognitive impairment, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences, Biological psychology
Abstract

BackgroundVariability in dementia rates across racial and ethnic groups has been estimated at 60%. Studies suggest disparities in Caribbean Hispanic and Black populations, but community-based data are limited.ObjectiveEstimate the prevalence of mild cognitive impairment (MCI) and dementia in the racially and ethnically diverse community-based Northern Manhattan Study cohort and examine sociodemographic, vascular risk factor, and brain imaging correlates.MethodsCases of MCI and dementia were adjudicated by a team of neuropsychologists and neurologists and prevalence was estimated across race/ethnic groups. Ordinal proportional odds models were used to estimate race/ethnic differences in the prevalence of MCI or dementia adjusting for sociodemographic variables (model 1), model 1 plus potentially modifiable vascular risk factors (model 2), and model 1 plus structural imaging markers of brain integrity (model 3).ResultsThere were 989 participants with cognitive outcome determinations (mean age 69±9 years; 68% Hispanic, 16% Black, 14% White; 62% women; mean (±SD) follow-up five (±0.6) years). Hispanic and Black participants had greater likelihood of MCI (20%) and dementia (5%) than White participants accounting for age and education differences. Hispanic participants had greater odds of MCI or dementia than both White and Black participants adjusting for sociodemographic variables, vascular risk factors, and brain imaging factors. White matter hyperintensity burden was significantly associated with greater odds of MCI or dementia (OR = 1.3, 1.1 to 1.6), but there was no significant interaction by race/ethnicity.ConclusionIn this diverse community-based cohort, cross-sectional data revealed significant race/ethnic disparities in the prevalence of MCI and dementia. Longer follow-up and incidence data are needed to further clarify these relationships.

Published
2021

25. Identifying local cognitive representations in the brain across age spans through voxel searchlights and representational similarity analysis

Author

Reno, Laura G, Habeck, Christian G, Stern, Yaakov, and Leeds, Daniel D

Subjects
cognitive science
Abstract

Localizing function in the brain has been an elusive long-term goal in the study of cognition. Prior studies have utilized four reference abilities (RAs) to capture cognition (Salthouse, 2009). Full-brain cortical networks have been tied to these abilities using common multi-voxel patterns across subjects in distinct age groups. Using voxel searchlights the current study explores purely local cortical representations of cognition, less commonly explored. This work analyzes 240 subjects’ responses to cognitive tasks from the four RAs. The current study further employs representational similarity analysis (RSA, Kriegeskorte, Mur, & Bandettini, 2008) to the similarity of brain activities from tasks within the same RA; RSA can capture representational consistencies within each subject even when exact voxel pattern may vary across subjects. We found distinct topographical localizations for each RA that were mostly consistent across age and suggested refinements of broader functional divisions of the brain from prior literature.

Published
2021

26. Women can bear a bigger burden: ante- and post-mortem evidence for reserve in the face of tau

Author

Digma, Leonardino A, Madsen, John R, Rissman, Robert A, Jacobs, Diane M, Brewer, James B, Banks, Sarah J, 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, and Oliver, Angela

Subjects
Biological Psychology, Psychology, Brain Disorders, Neurodegenerative, Alzheimer's Disease, Neurosciences, Acquired Cognitive Impairment, Women's Health, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Clinical Research, tau, verbal memory, sex differences, Alzheimer's disease, Alzheimer’s Disease Neuroimaging Initiative, Alzheimer’s disease, Clinical sciences, Biological psychology
Abstract

In this study, we aimed to assess whether women are able to withstand more tau before exhibiting verbal memory impairment. Using data from 121 amyloid-β-positive Alzheimer's Disease Neuroimaging Initiative participants, we fit a linear model with Rey Auditory Verbal Learning Test score as the response variable and tau-PET standard uptake value ratio as the predictor and took the residuals as an estimate of verbal memory reserve for each subject. Women demonstrated higher reserve (i.e. residuals), whether the Learning (t = 2.78, P = 0.006) or Delay (t = 2.14, P = 0.03) score from the Rey Auditory Verbal Learning Test was used as a measure of verbal memory ability. To validate these findings, we examined 662 National Alzheimer's Coordinating Center participants with a C2/C3 score (Consortium to Establish a Registry for Alzheimer's Disease) at autopsy. We stratified our National Alzheimer's Coordinating Center sample into Braak 1/2, Braak 3/4 and Braak 5/6 subgroups. Within each subgroup, we compared Logical Memory scores between men and women. Men had worse verbal memory scores within the Braak 1/2 (Logical Memory Immediate: β = -5.960 ± 1.517, P

Published
2020

30. Trajectories of Occupational Cognitive Demands and Risk of Mild Cognitive Impairment and Dementia in Later Life

Author

Edwin, Trine H., primary, Håberg, Asta K., additional, Zotcheva, Ekaterina, additional, Bratsberg, Bernt, additional, Jugessur, Astanand, additional, Engdahl, Bo, additional, Bowen, Catherine, additional, Selbæk, Geir, additional, Kohler, Hans-Peter, additional, Harris, Jennifer R., additional, Tom, Sarah E., additional, Krokstad, Steinar, additional, Mekonnen, Teferi, additional, Stern, Yaakov, additional, Skirbekk, Vegard F., additional, and Strand, Bjørn H., additional

Published
2024
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33. A randomized trial of blood donor iron repletion on red cell quality for transfusion and donor cognition and well-being

Author

Hod, Eldad A., Brittenham, Gary M., Bitan, Zachary C., Feit, Yona, Gaelen, Jordan I., La Carpia, Francesca, Sandoval, Luke A., Zhou, Alice T., Soffing, Mark, Mintz, Akiva, Schwartz, Joseph, Eng, Connie, Scotto, Marta, Caccappolo, Elise, Habeck, Christian, Stern, Yaakov, McMahon, Donald J., Kessler, Debra A., Shaz, Beth H., Francis, Richard O., and Spitalnik, Steven L.

Published
2022
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35. Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need.

Author

Babulal, Ganesh M, Quiroz, Yakeel T, Albensi, Benedict C, Arenaza-Urquijo, Eider, Astell, Arlene J, Babiloni, Claudio, Bahar-Fuchs, Alex, Bell, Joanne, Bowman, Gene L, Brickman, Adam M, Chételat, Gaël, Ciro, Carrie, Cohen, Ann D, Dilworth-Anderson, Peggye, Dodge, Hiroko H, Dreux, Simone, Edland, Steven, Esbensen, Anna, Evered, Lisbeth, Ewers, Michael, Fargo, Keith N, Fortea, Juan, Gonzalez, Hector, Gustafson, Deborah R, Head, Elizabeth, Hendrix, James A, Hofer, Scott M, Johnson, Leigh A, Jutten, Roos, Kilborn, Kerry, Lanctôt, Krista L, Manly, Jennifer J, Martins, Ralph N, Mielke, Michelle M, Morris, Martha Clare, Murray, Melissa E, Oh, Esther S, Parra, Mario A, Rissman, Robert A, Roe, Catherine M, Santos, Octavio A, Scarmeas, Nikolaos, Schneider, Lon S, Schupf, Nicole, Sikkes, Sietske, Snyder, Heather M, Sohrabi, Hamid R, Stern, Yaakov, Strydom, Andre, Tang, Yi, Terrera, Graciela Muniz, Teunissen, Charlotte, Melo van Lent, Debora, Weinborn, Michael, Wesselman, Linda, Wilcock, Donna M, Zetterberg, Henrik, O'Bryant, Sid E, and International Society to Advance Alzheimer's Research and Treatment, Alzheimer's Association

Subjects
International Society to Advance Alzheimer's Research and Treatment, Alzheimer's Association, Humans, Alzheimer Disease, Biomedical Research, Aged, Continental Population Groups, Ethnic Groups, Healthcare Disparities, Biomarkers, Alzheimer's disease, Alzheimer's related dementias, Diversity, Ethnicity, Ethnoracial, Translational, Underserved, Geriatrics, Clinical Sciences, Neurosciences
Abstract

Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise "state-of-the-science" report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations.

Published
2019

42. Detection of neurophysiological markers of cognitive reserve: an EEG study.

Author

Osamu Katayama, Stern, Yaakov, Habeck, Christian, Coors, Annabell, Sangyoon Lee, Kenji Harada, Keitaro Makino, Kouki Tomida, Masanori Morikawa, Ryo Yamaguchi, Chiharu Nishijima, Yuka Misu, Kazuya Fujii, Takayuki Kodama, and Hiroyuki Shimada

Subjects
BRAIN physiology, COGNITIVE testing, RESEARCH funding, NEUROPHYSIOLOGY, ELECTROENCEPHALOGRAPHY, EPISODIC memory, DESCRIPTIVE statistics, GERIATRIC Depression Scale, HIPPOCAMPUS (Brain), PSYCHOLOGICAL tests, OLD age
Abstract

Background and objectives: Cognitive reserve (CR) is a property of the brain that allows for better-than-expected cognitive performance relative to the degree of brain change over the course of life. However, neurophysiological markers of CR remain under-investigated. Electroencephalography (EEG) features may function as suitable neurophysiological markers of CR. To assess this, we investigated whether the dorsal attention network (DAN) and ventral attention network (VAN) activities, as measured during resting-state EEG, moderate the relationship between hippocampal volume and episodic memory. Methods: Participants were recruited as part of the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. Hippocampal volume was determined using magnetic MRI, and episodic memory was measured using word lists. After testing the effect of hippocampal volume on memory performance using multiple regression analysis, we evaluated the interactions between hippocampal volume and DAN and VAN network activities. We further used the Johnson-Neyman technique to quantify the moderating effects of DAN and VAN network activities on the relationship between hippocampal volume and word list memory, as well as to identify specific ranges of DAN and VAN network activity with significant hippocampal-memory association. Results: A total of 449 participants were included in this study. Our analysis revealed significant moderation of DAN with a slope of β = -0.00012 (95% CI: -0.00024; -0.00001, p = 0.040), and VAN with a slope of β = 0.00014 (95% CI: 0.00001; 0.00026, p = 0.031). Further, we found that a larger hippocampal volume was associated with improved memory performance, and that this association became stronger as the DAN activity decreased until a limit of DAN activity of 944.9, after which the hippocampal volume was no longer significantly related to word-list memory performance. For the VAN, we found that a higher hippocampal volume was more strongly associated with better memory performance when VAN activity was higher. However, when VAN activity extended beyond -914.6, the hippocampal volume was no longer significantly associated with word-list memory. Discussion: Our results suggest that attentional networks help to maintain memory performance in the face of age-related structural decline, meeting the criteria for the neural implementation of cognitive reserve. [ABSTRACT FROM AUTHOR]

Published
2024
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43. Remote Associations Between Tau and Cortical Amyloid-β Are Stage-Dependent

Author

Hojjati, Seyed Hani, primary, Chiang, Gloria C., additional, Butler, Tracy A., additional, de Leon, Mony, additional, Gupta, Ajay, additional, Li, Yi, additional, Sabuncu, Mert R., additional, Feiz, Farnia, additional, Nayak, Siddharth, additional, Shteingart, Jacob, additional, Ozoria, Sindy, additional, Gholipour Picha, Saman, additional, Stern, Yaakov, additional, Luchsinger, José A., additional, Devanand, Davangere P., additional, and Razlighi, Qolamreza R., additional

Published
2024
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44. Microglia measured by TSPO PET are associated with Alzheimer's disease pathology and mediate key steps in a disease progression model

Author

Rossano, Samantha M., primary, Johnson, Aubrey S., additional, Smith, Anna, additional, Ziaggi, Galen, additional, Roetman, Andrew, additional, Guzman, Diana, additional, Okafor, Amarachukwu, additional, Klein, Julia, additional, Tomljanovic, Zeljko, additional, Stern, Yaakov, additional, Brickman, Adam M., additional, Lee, Seonjoo, additional, Kreisl, William C., additional, and Lao, Patrick, additional

Published
2024
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47. Medicare Expenditure Correlates of Atrophy and Cerebrovascular Disease in Older Adults

Author

Last, Briana S, Rubio, Maria-José García, Zhu, Carolyn W, Cosentino, Stephanie, Manly, Jennifer J, DeCarli, Charles, Stern, Yaakov, and Brickman, Adam M

Subjects
Biological Psychology, Clinical and Health Psychology, Cognitive and Computational Psychology, Psychology, Neurosciences, Acquired Cognitive Impairment, Clinical Research, Brain Disorders, Aging, Health Services, Biomedical Imaging, Age Factors, Aged, 80 and over, Atrophy, Brain, Cerebrovascular Disorders, Female, Health Expenditures, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Medicare, United States, Clinical Sciences, Public Health and Health Services, Experimental Psychology, Biological psychology, Clinical and health psychology, Cognitive and computational psychology
Abstract

Background/Study Context: Magnetic resonance imaging (MRI) markers of cerebrovascular disease and atrophy are common in older adults and are associated with cognitive and medical burden. However, the extent to which they are related to health care expenditures has not been examined. We studied whether increased Medicare expenditures were associated with brain markers of atrophy and cerebrovascular disease in older adults.MethodsA subset of participants (n = 592; mean age = 80 years; 66% women) from the Washington Heights Inwood Columbia Aging Project (WHICAP), a community-based observational study of aging in upper Manhattan, received high-resolution MRI and had Medicare expenditure data on file. We examined the relationship of common markers of cerebrovascular disease (i.e., white matter hyperintensities and presence of infarcts) and atrophy (i.e., whole brain and hippocampal volume) with Medicare expenditure data averaged over a 10-year period. Main outcome measures were (a) mean Medicare payment per year across the 10-year interval; (b) mean payment for outpatient care per year; and (c) mean payment for inpatient care per year of visit. In addition, we calculated the ratio of mean inpatient spending to mean outpatient spending as well as the ratio of mean inpatient spending to mean total Medicare spending.ResultsIncreased Medicare spending was associated with higher white matter hyperintensity volume, presence of cerebral infarcts, and smaller total brain volume. When examining specific components of Medicare expenditures, we found that inpatient spending was strongly associated with white matter hyperintensity volume and that increased ratios of inpatient to outpatient and inpatient to total spending were associated with infarcts.ConclusionMedicare costs are related to common markers of "silent" cerebrovascular disease and atrophy.

Published
2017

48. Blood Pressure Control in Aging Predicts Cerebral Atrophy Related to Small-Vessel White Matter Lesions

Author

Kern, Kyle C, Wright, Clinton B, Bergfield, Kaitlin L, Fitzhugh, Megan C, Chen, Kewei, Moeller, James R, Nabizadeh, Nooshin, Elkind, Mitchell SV, Sacco, Ralph L, Stern, Yaakov, DeCarli, Charles S, and Alexander, Gene E

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Biomedical Imaging, Alzheimer's Disease Related Dementias (ADRD), Aging, Neurosciences, Neurodegenerative, Cerebrovascular, Cardiovascular, Dementia, Hypertension, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Behavioral and Social Science, Basic Behavioral and Social Science, Brain Disorders, Vascular Cognitive Impairment/Dementia, Alzheimer's Disease, Acquired Cognitive Impairment, Neurological, white matter hyperintensities, brain atrophy, hypertension, cerebrovascular disease, cognition, aging, scaled subprofile model, voxel-based morphometry, Biochemistry and Cell Biology, Cognitive Sciences, Biological psychology
Abstract

Cerebral small-vessel damage manifests as white matter hyperintensities and cerebral atrophy on brain MRI and is associated with aging, cognitive decline and dementia. We sought to examine the interrelationship of these imaging biomarkers and the influence of hypertension in older individuals. We used a multivariate spatial covariance neuroimaging technique to localize the effects of white matter lesion load on regional gray matter volume and assessed the role of blood pressure control, age and education on this relationship. Using a case-control design matching for age, gender, and educational attainment we selected 64 participants with normal blood pressure, controlled hypertension or uncontrolled hypertension from the Northern Manhattan Study cohort. We applied gray matter voxel-based morphometry with the scaled subprofile model to (1) identify regional covariance patterns of gray matter volume differences associated with white matter lesion load, (2) compare this relationship across blood pressure groups, and (3) relate it to cognitive performance. In this group of participants aged 60-86 years, we identified a pattern of reduced gray matter volume associated with white matter lesion load in bilateral temporal-parietal regions with relative preservation of volume in the basal forebrain, thalami and cingulate cortex. This pattern was expressed most in the uncontrolled hypertension group and least in the normotensives, but was also more evident in older and more educated individuals. Expression of this pattern was associated with worse performance in executive function and memory. In summary, white matter lesions from small-vessel disease are associated with a regional pattern of gray matter atrophy that is mitigated by blood pressure control, exacerbated by aging, and associated with cognitive performance.

Published
2017

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