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1. 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

3. Long-term clinical outcomes and cost-effectiveness of catheter vs thoracoscopic surgical ablation in long-standing persistent atrial fibrillation using continuous cardiac monitoring: CASA-AF randomized controlled trial

Author

Yahdev, Rashmi, Rahman-Halley, Shelley, Wong, Joyce, Opel, Aaisha, Kaba, Riyaz, Nyktari, Eva, Cambronero-Cortinas, Esther, Izgi, Cemil, Fairbairn, Timothy, Benton, Joanne, Chester, Ruth, Cunliffe, Eliane, Edmondson, Lucy, Gill, Matthew, Griffiths, Vicky, Harman, Rebecca, Huggett, Catherine, Keegan, Jenny, Kirby, Kevin, Lascelles, Karen, Manivarmane, Ramasamy, Munteanu, Iulia, O’Brien, Karen, Phyl, Tess, Rahneva, Tsveta, Riley, Cheryl, Rogers, Paula, Smith, Katherine, Wage, Rick, West, Cathy, Yakupoglu, Yakup, Yang, Guang, Audraite, Audra, Belchambers, Sandra, Hughes, Susan, Morgan, Maureen, Ronayne, Christina, Shaw, Rob, Simkus, Paulinus, Taylerson, Clive, Bruce, Chloe, McGregor, Andrew, Thomson, Catherine, Granville, Hollie, Snell, Alice, John, Sophia, Monteiro, Christiana, Augustine, Grace, Sutton, Nichola, Boyalla, Vennela, Haldar, Shouvik, Khan, Habib, Kralj-Hans, Ines, Banya, Winston, Lord, Joanne, Satishkumar, Anitha, Bahrami, Toufan, De Souza, Anthony, Clague, Jonathan R., Francis, Darrel P., Hussain, Wajid, Jarman, Julian W., Jones, David G., Chen, Zhong, Mediratta, Neeraj, Hyde, Jonathan, Lewis, Michael, Mohiaddin, Raad, Salukhe, Tushar V., Markides, Vias, McCready, James, Gupta, Dhiraj, and Wong, Tom

Published
2024
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4. 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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6. 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

7. Aspirin to target arterial events in chronic kidney disease (ATTACK): study protocol for a multicentre, prospective, randomised, open-label, blinded endpoint, parallel group trial of low-dose aspirin vs. standard care for the primary prevention of cardiovascular disease in people with chronic kidney disease

Author

Gallagher, Hugh, Dumbleton, Jennifer, Maishman, Tom, Whitehead, Amy, Moore, Michael V., Fuat, Ahmet, Fitzmaurice, David, Henderson, Robert A., Lord, Joanne, Griffith, Kathryn E., Stevens, Paul, Taal, Maarten W., Stevenson, Diane, Fraser, Simon D., Lown, Mark, Hawkey, Christopher J., and Roderick, Paul J.

Published
2022
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9. Long-term clinical outcomes and cost-effectiveness of catheter vs thoracoscopic surgical ablation in long-standing persistent atrial fibrillation using continuous cardiac monitoring: CASA-AF randomized controlled trial.

Author

Boyalla, Vennela, Haldar, Shouvik, Khan, Habib, Kralj-Hans, Ines, Banya, Winston, Lord, Joanne, Satishkumar, Anitha, Bahrami, Toufan, De Souza, Anthony, Clague, Jonathan R., Francis, Darrel P., Hussain, Wajid, Jarman, Julian W., Jones, David G., Chen, Zhong, Mediratta, Neeraj, Hyde, Jonathan, Lewis, Michael, Mohiaddin, Raad, and Salukhe, Tushar V.

Abstract

Long-term clinical outcomes of catheter ablation (CA) compared to thoracoscopic surgical ablation (SA) to treat patients with long-standing persistent atrial fibrillation (LSPAF) are not known. The purpose of this study was to compare the long-term (36-month) clinical efficacy, quality of life, and cost-effectiveness of SA and CA in LSPAF. Participants were followed up for 3 years using implantable loop recorders and questionnaires to assess the change in quality of life. Intention-to-treat analyses were used to report the findings. Of the 115 patients with LSPAF treated, 104 (90.4%) completed 36-month follow-up [CA: n = 57 (95%); SA: n = 47 (85%)]. After a single procedure without antiarrhythmic drugs, 7 patients (12%) in the CA arm and 5 (11%) in the SA arm [hazard ratio 1.22; 95% confidence interval (CI) 0.81–1.83; P =.41] were free from atrial fibrillation/tachycardia (AF/AT) ≥30 seconds at 36 months. Thirty-three patients (58%) in the CA arm and 26 (55%) in the SA arm (hazard ratio 1.04; 95% CI 0.57–1.88; P =.91) had their AF/AT burden reduced by ≥75%. The overall impact on health-related quality of life was similar, with mean quality-adjusted life year estimates of 2.45 (95% CI 2.31–2.59) for CA and 2.32 (95% CI 2.13–2.52) for SA. Estimated costs were higher for SA (mean £24,682; 95% CI £21,746–£27,618) than for CA (mean £18,002; 95% CI £15,422–£20,581). In symptomatic LSPAF, CA and SA were equally effective at achieving arrhythmia outcomes (freedom from AF/AT ≥30 seconds and ≥75% burden reduction) after a single procedure without antiarrhythmic drugs. However, SA is significantly more costly than CA. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): a multicentre, double-blind, randomised, phase 3 trial

Author

Price, Gillian, Shaw, Paul, Cave, Judith, Naik, Jay, Ford, Amy, Geldhart, Tom, Dancey, Gairin, Papadatos, Dionysis, Polychronis, Andy, Jankowska, Petra, Scott, Angela, Gardiner, Jill, Cominos, Mathilda, Campbell, Lynn, MacGregor, Carol, Mullholand, Lois, Chitnis, Meenali, Dougherty, Gary, Fennell, Dean A, Ewings, Sean, Ottensmeier, Christian, Califano, Raffaele, Hanna, Gerard G, Hill, Kayleigh, Danson, Sarah, Steele, Nicola, Nye, Mavis, Johnson, Lucy, Lord, Joanne, Middleton, Calley, Szlosarek, Peter, Chan, Sam, Gaba, Aarti, Darlison, Liz, Wells-Jordan, Peter, Richards, Cathy, Poile, Charlotte, Lester, Jason F, and Griffiths, Gareth

Published
2021
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11. Statistical methods for body mass index: a selective review of the literature

Author

Yu, Keming, Alhamzawi, Rahim, Becker, Frauke, and Lord, Joanne

Subjects
Statistics - Applications
Abstract

Obesity rates have been increasing over recent decades, causing significant concern among policy makers. Excess body fat, commonly measured by body mass index (BMI), is a major risk factor for several common disorders including diabetes and cardiovascular disease, placing a substantial burden on health care systems. % Body mass index (BMI) is one indicator for excess body fat. To guide effective public health action, we need to understand the complex system of intercorrelated influences on BMI. This paper will review both classical and modern statistical methods for BMI analysis, highlighting that most of the classical methods are simple and easy to implement but ignore the complexity of data and structure, whereas modern methods do take complexity into consideration but can be difficult to implement. A series of case studies are presented to illustrate these methods and some potentially useful new models are suggested.

Published
2014

12. Accelerating rates of cognitive decline and imaging markers associated with &bgr;-amyloid pathology

Author

Insel, Philip S, Mattsson, Niklas, Mackin, R Scott, Schöll, Michael, Nosheny, Rachel L, Tosun, Duygu, Donohue, Michael C, Aisen, Paul S, Jagust, William J, Weiner, Michael W, 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, Liu, Enchi, Montine, Tom, Gamst, Anthony, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Harvey, Danielle, Kornak, John, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Bandy, Dan, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Cairns, Nigel J, Taylor-Reinwald, Lisa, Trojanowki, JQ, Shaw, Les, Lee, Virginia MY, Korecka, Magdalena, Crawford, Karen, Neu, Scott, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J, Molchan, Susan, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Dolen, Sara, Schneider, Lon S, Pawluczyk, Sonia, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Heidebrink, Judith L, Lord, Joanne L, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S, Bell, Karen L, Morris, John C, Ances, Beau, Carroll, Maria, Leon, Sue, Mintun, Mark A, Schneider, Stacy, Marson, Daniel, and Griffith, Randall

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Acquired Cognitive Impairment, Dementia, Neurodegenerative, Biomedical Imaging, Brain Disorders, Aging, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurosciences, Neurological, Aged, Amyloid beta-Peptides, Aniline Compounds, Atrophy, Biomarkers, Brain, Cognition, Cognitive Dysfunction, Disease Progression, Ethylene Glycols, Female, Fluorodeoxyglucose F18, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Mental Status Schedule, Neuropsychological Tests, Peptide Fragments, Positron-Emission Tomography, Radiopharmaceuticals, Regression Analysis, Alzheimer's Disease Neuroimaging Initiative, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveTo estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate.MethodsIn 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression.ResultsRates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloid positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline.ConclusionsA considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ42. Future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline.

Published
2016

13. Better verbal memory in women than men in MCI despite similar levels of hippocampal atrophy

Author

Sundermann, Erin E, Biegon, Anat, Rubin, Leah H, Lipton, Richard B, Mowrey, Wenzhu, Landau, Susan, Maki, Pauline M, 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, Liu, Enchi, Montine, Tom, Gamst, Anthony, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Harvey, Danielle, Kornak, John, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Bandy, Dan, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Cairns, Nigel J, Taylor-Reinwald, Lisa, Trojanowki, JQ, Shaw, Les, Lee, Virginia MY, Korecka, Magdalena, Crawford, Karen, Neu, Scott, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J, Molchan, Susan, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Dolen, Sara, Schneider, Lon S, Pawluczyk, Sonia, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Heidebrink, Judith L, Lord, Joanne L, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S, Bell, Karen L, Morris, John C, Ances, Beau, Carroll, Maria, Leon, Sue, Mintun, Mark A, Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, and Mitsis, Effie

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Prevention, Aging, Behavioral and Social Science, Clinical Research, Alzheimer's Disease, Brain Disorders, Acquired Cognitive Impairment, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Clinical Trials and Supportive Activities, Dementia, 2.1 Biological and endogenous factors, Aetiology, Neurological, Aged, Aged, 80 and over, Atrophy, Cognitive Dysfunction, Cross-Sectional Studies, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Memory, Middle Aged, Sex Characteristics, Verbal Learning, Alzheimer's Disease Neuroimaging Initiative, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveTo examine sex differences in the relationship between clinical symptoms related to Alzheimer disease (AD) (verbal memory deficits) and neurodegeneration (hippocampal volume/intracranial volume ratio [HpVR]) across AD stages.MethodsThe sample included 379 healthy participants, 694 participants with amnestic mild cognitive impairment (aMCI), and 235 participants with AD and dementia from the Alzheimer's Disease Neuroimaging Initiative who completed the Rey Auditory Verbal Learning Test (RAVLT). Cross-sectional analyses were conducted using linear regression to examine the interaction between sex and HpVR on RAVLT across and within diagnostic groups adjusting for age, education, and APOE ε4 status.ResultsAcross groups, there were significant sex × HpVR interactions for immediate and delayed recall (p < 0.01). Women outperformed men among individuals with moderate to larger HpVR, but not among individuals with smaller HpVR. In diagnosis-stratified analyses, the HpVR × sex interaction was significant in the aMCI group, but not in the control or AD dementia groups, for immediate and delayed recall (p < 0.01). Among controls, women outperformed men on both outcomes irrespective of HpVR (p < 0.001). In AD dementia, better RAVLT performance was independently associated with female sex (immediate, p = 0.04) and larger HpVR (delayed, p = 0.001).ConclusionWomen showed an advantage in verbal memory despite evidence of moderate hippocampal atrophy. This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages.

Published
2016

14. Periventricular hyperintensities are associated with elevated cerebral amyloid

Author

Marnane, Michael, Al-Jawadi, Osama O, Mortazavi, Shervin, Pogorzelec, Kathleen J, Wang, Bing Wei, Feldman, Howard H, Hsiung, Ging-Yuek R, 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, Liu, Enchi, Montine, Tom, Gamst, Anthony, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Harvey, Danielle, Kornak, John, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Bandy, Dan, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Cairns, Nigel J, Taylor-Reinwald, Lisa, Trojanowki, JQ, Shaw, Les, Lee, Virginia MY, Korecka, Magdalena, Crawford, Karen, Neu, Scott, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J, Molchan, Susan, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Dolen, Sara, Schneider, Lon S, Pawluczyk, Sonia, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Heidebrink, Judith L, Lord, Joanne L, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S, Bell, Karen L, Morris, John C, Ances, Beau, Carroll, Maria, Leon, Sue, Mintun, Mark A, Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, and Mitsis, Effie

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Aging, Clinical Research, Alzheimer's Disease, Neurosciences, Brain Disorders, Acquired Cognitive Impairment, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, 2.1 Biological and endogenous factors, Aetiology, Neurological, Adult, Aged, Aged, 80 and over, Amyloid beta-Peptides, Biomarkers, Cerebral Ventricles, Cognitive Dysfunction, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Positron-Emission Tomography, Prospective Studies, Alzheimer's Disease Neuroimaging Initiative, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveTo investigate the association between periventricular white mater hyperintensities (PVWMH) and biomarkers of elevated cerebral β-amyloid (Aβ) in the Alzheimer's Disease Neuroimaging Initiative, a large prospective multicenter observational study.MethodsThe burden of frontal, parietal, and occipital PVWMH on 3T fluid-attenuated inversion recovery MRI was evaluated in 698 cognitively normal participants and participants with mild cognitive impairment (MCI) using a novel semiquantitative visual rating scale. Results were correlated with CSF-Aβ, florbetapir-PET, and fluorodeoxyglucose (FDG)-PET.ResultsIncreased burden of parietal, occipital, and frontal PVWMH was associated with elevated cerebral amyloid evidenced by high florbetapir-PET signal (p < 0.01) and low CSF-Aβ (p < 0.01). In logistic regression models, including PVWMH, age, sex, APOE status, vascular risk factors, pulse pressure, vascular secondary prevention medications, education, ethnicity, and race, parietal, occipital, and frontal PVWMH burden was independently associated with high florbetapir-PET uptake (p < 0.05). In a similar logistic regression model, parietal and occipital (p < 0.05) but not frontal (p = 0.05) PVWMH were independently associated with CSF-Aβ. Weaker associations were found between parieto-occipital PVWMH and elevated CSF-tau (p < 0.05) and occipital PVWMH and elevated CSF-phospho-tau (p < 0.05). PVWMH were associated with cerebral hypometabolism on FDG-PET independent of CSF-Aβ levels (p < 0.05). Absolute and consistency of agreement intraclass correlation coefficients were, respectively, 0.83 and 0.83 for frontal, 0.78 and 0.8 for parietal, and 0.45 and 0.75 for occipital PVWMH measurements.ConclusionsIncreased PVWMH were associated with elevated cerebral amyloid independent of potential confounders such as age, APOE genotype, and vascular risk factors. The mechanisms underlying the association between PVWMH and cerebral amyloid remain to be clarified.

Published
2016

15. Memory, executive, and multidomain subtle cognitive impairment

Author

Toledo, Jon B, Bjerke, Maria, Chen, Kewei, Rozycki, Martin, Jack, Clifford R, Weiner, Michael W, Arnold, Steven E, Reiman, Eric M, Davatzikos, Christos, Shaw, Leslie M, Trojanowski, John Q, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Jagust, William, Trojanowki, John Q, Toga, Arthur W, Beckett, Laurel, Green, Robert C, Saykin, Andrew J, Morris, John, Liu, Enchi, Montine, Tom, Gamst, Anthony, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Harvey, Danielle, Kornak, John, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Bandy, Dan, Koeppe, Robert A, Foster, Norm, Mathis, Chet, Cairns, Nigel J, Taylor-Reinwald, Lisa, Trojanowki, JQ, Shaw, Les, Lee, Virginia MY, Korecka, Magdalena, Crawford, Karen, Neu, Scott, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J, Molchan, Susan, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Dolen, Sara, Schneider, Lon S, Pawluczyk, Sonia, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Heidebrink, Judith L, Lord, Joanne L, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S, Bell, Karen L, Morris, John C, Ances, Beau, Leon, Sue, Schneider, Stacy, Marson, Daniel, Griffith, Randall, and Clark, David

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Biomedical Imaging, Aging, Behavioral and Social Science, Clinical Research, Alzheimer's Disease, Acquired Cognitive Impairment, Brain Disorders, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Mental health, Aged, Aged, 80 and over, Alzheimer Disease, Biomarkers, Brain, Cognition Disorders, Cognitive Dysfunction, Disease Progression, Executive Function, Female, Humans, Magnetic Resonance Imaging, Male, Memory Disorders, Multimodal Imaging, Positron-Emission Tomography, Alzheimer's Disease Neuroimaging Initiative, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveWe studied the biomarker signatures and prognoses of 3 different subtle cognitive impairment (SCI) groups (executive, memory, and multidomain) as well as the subjective memory complaints (SMC) group.MethodsWe studied 522 healthy controls in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cutoffs for executive, memory, and multidomain SCI were defined using participants who remained cognitively normal (CN) for 7 years. CSF Alzheimer disease (AD) biomarkers, composite and region-of-interest (ROI) MRI, and fluorodeoxyglucose-PET measures were compared in these participants.ResultsUsing a stringent cutoff (fifth percentile), 27.6% of the ADNI participants were classified as SCI. Most single ROI or global-based measures were not sensitive to detect differences between groups. Only MRI-SPARE-AD (Spatial Pattern of Abnormalities for Recognition of Early AD), a quantitative MRI pattern-based global index, showed differences between all groups, excluding the executive SCI group. Atrophy patterns differed in memory SCI and SMC. The CN and the SMC groups presented a similar distribution of preclinical dementia stages. Fifty percent of the participants with executive, memory, and multidomain SCI progressed to mild cognitive impairment or dementia at 7, 5, and 2 years, respectively.ConclusionsOur results indicate that (1) the different SCI categories have different clinical prognoses and biomarker signatures, (2) longitudinally followed CN subjects are needed to establish clinical cutoffs, (3) subjects with SMC show a frontal pattern of brain atrophy, and (4) pattern-based analyses outperform commonly used single ROI-based neuroimaging biomarkers and are needed to detect initial stages of cognitive impairment.

Published
2015

16. Brain structure and function as mediators of the effects of amyloid on memory

Author

Mattsson, Niklas, Insel, Philip S, Aisen, Paul S, Jagust, William, Mackin, Scott, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Jack, Clifford R, Trojanowki, John Q, Toga, Arthur W, Beckett, Laurel, Green, Robert C, Saykin, Andrew J, Morris, John, Liu, Enchi, Montine, Tom, Gamst, Anthony, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Harvey, Danielle, Kornak, John, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Bandy, Dan, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Cairns, Nigel J, Taylor-Reinwald, Lisa, Trojanowki, JQ, Shaw, Les, Lee, Virginia MY, Korecka, Magdalena, Crawford, Karen, Neu, Scott, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J, Molchan, Susan, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Dolen, Sara, Schneider, Lon S, Pawluczyk, Sonia, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Heidebrink, Judith L, Lord, Joanne L, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S, Bell, Karen L, Morris, John C, Ances, Beau, Carroll, Maria, Leon, Sue, Mintun, Mark A, Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Mitsis, Effie, and Romirowsky, Aliza

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Biomedical Imaging, Aging, Alzheimer's Disease, Acquired Cognitive Impairment, Brain Disorders, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, 2.1 Biological and endogenous factors, Aetiology, Neurological, Mental health, Aged, Aged, 80 and over, Amyloid beta-Peptides, Brain, Cohort Studies, Female, Follow-Up Studies, Humans, Male, Memory, Episodic, Middle Aged, Prospective Studies, Radionuclide Imaging, Alzheimer's Disease Neuroimaging Initiative, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveThe objective of this study was to test whether effects of β-amyloid (Aβ) pathology on episodic memory were mediated by metabolism and gray matter volume in the early stages of Alzheimer disease.MethodsThis was a prospective cohort study. We measured baseline Aβ (using florbetapir-PET), brain function (using fluorodeoxyglucose-PET), and brain structure (using MRI). A mediation analysis was performed to test whether statistical effects of Aβ positivity on cross-sectional and longitudinal episodic memory were mediated by hypometabolism or regional gray matter volume in cognitively healthy controls (CN, n = 280) and mild cognitive impairment (MCI, n = 463).ResultsLower memory scores were associated with Aβ positivity (CN, mildly; MCI, strongly), smaller gray matter volumes (CN, few regions, including hippocampus; MCI, widespread), and hypometabolism. Smaller volumes and hypometabolism mediated effects of Aβ in MCI but not in CN. The strongest individual regions mediated up to approximately 25%. A combination of brain structure and function mediated up to approximately 40%. In several regions, gray matter atrophy and hypometabolism predicted episodic memory without being associated (at p < 0.05) with Aβ positivity.ConclusionsChanges in brain structure and function appear to be, in part, downstream events from Aβ pathology, ultimately resulting in episodic memory deficits. However, Aβ pathology is also strongly related to memory deficits through mechanisms that are not quantified by these imaging measurements, and episodic memory decline is partly caused by Alzheimer disease-like brain changes independently of Aβ pathology.

Published
2015

17. Brain amyloidosis ascertainment from cognitive, imaging, and peripheral blood protein measures

Author

Apostolova, Liana G, Hwang, Kristy S, Avila, David, Elashoff, David, Kohannim, Omid, Teng, Edmond, Sokolow, Sophie, Jack, Clifford R, Jagust, William J, Shaw, Leslie, Trojanowski, John Q, Weiner, Michael W, Thompson, Paul M, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Jagust, Wiliam, Trojanowki, JQ, Toga, Arthur W, Beckett, Laurel, Green, Robert C, Gamst, Anthony, Sakin, Andrew J, Morris, John, Potter, William Z, Montine, Tom, Donohue, Michael, Walter, Sarah, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Bandy, Dan, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Cairns, Nigel J, Taylor-Reinwald, Lisa, Shaw, Lee, Lee, Virginia M-Y, Korecka, Magdalena, Crawford, Karen, Neu, Scott, Harvey, Danielle, Kornak, John, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J, Molchan, Susan, Kaye, Jeffrey, Dolen, Sara, Quinn, Joseph, Schneider, Lon, Pawluczyk, Sonia, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Heidebrink, Judith L, Lord, Joanne L, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S, Bell, Karen L, Mintun, Mark A, Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Tang, Cheuk, Marzloff, George, deToledo-Morrell, Leyla, Shah, Raj C, Duara, Ranjan, Varon, Daniel, Robers, Peggy, Albert, Marilyn S, Kozauer, Nicholas, Zerrate, Maria, Rusinek, Henry, de Leon, Mony J, De Santi, Susan M, Doraiswamy, P Murali, Petrella, Jeffrey R, Aiello, Marilyn, Arnold, Steve, and Karlawish, Jason H

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Biomedical Imaging, Aging, Behavioral and Social Science, Clinical Research, Alzheimer's Disease, Acquired Cognitive Impairment, Brain Disorders, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, 4.2 Evaluation of markers and technologies, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Neurological, Aged, Algorithms, Alzheimer Disease, Amyloid beta-Peptides, Amyloidosis, Aniline Compounds, Biomarkers, Brain, Cognition, Cognitive Dysfunction, Cohort Studies, Databases, Factual, Disease Progression, Female, Humans, Male, Neuropsychological Tests, Pattern Recognition, Automated, Peptide Fragments, Positron-Emission Tomography, Sensitivity and Specificity, Thiazoles, Alzheimer's Disease Neuroimaging Initiative, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

BackgroundThe goal of this study was to identify a clinical biomarker signature of brain amyloidosis in the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) mild cognitive impairment (MCI) cohort.MethodsWe developed a multimodal biomarker classifier for predicting brain amyloidosis using cognitive, imaging, and peripheral blood protein ADNI1 MCI data. We used CSF β-amyloid 1-42 (Aβ42) ≤ 192 pg/mL as proxy measure for Pittsburgh compound B (PiB)-PET standard uptake value ratio ≥ 1.5. We trained our classifier in the subcohort with CSF Aβ42 but no PiB-PET data and tested its performance in the subcohort with PiB-PET but no CSF Aβ42 data. We also examined the utility of our biomarker signature for predicting disease progression from MCI to Alzheimer dementia.ResultsThe CSF training classifier selected Mini-Mental State Examination, Trails B, Auditory Verbal Learning Test delayed recall, education, APOE genotype, interleukin 6 receptor, clusterin, and ApoE protein, and achieved leave-one-out accuracy of 85% (area under the curve [AUC] = 0.8). The PiB testing classifier achieved an AUC of 0.72, and when classifier self-tuning was allowed, AUC = 0.74. The 36-month disease-progression classifier achieved AUC = 0.75 and accuracy = 71%.ConclusionsAutomated classifiers based on cognitive and peripheral blood protein variables can identify the presence of brain amyloidosis with a modest level of accuracy. Such methods could have implications for clinical trial design and enrollment in the near future.Classification of evidenceThis study provides Class II evidence that a classification algorithm based on cognitive, imaging, and peripheral blood protein measures identifies patients with brain amyloid on PiB-PET with moderate accuracy (sensitivity 68%, specificity 78%).

Published
2015

18. Mild cognitive impairment with suspected nonamyloid pathology (SNAP)

Author

Caroli, Anna, Prestia, Annapaola, Galluzzi, Samantha, Ferrari, Clarissa, van der Flier, Wiesje M, Ossenkoppele, Rik, Van Berckel, Bart, Barkhof, Frederik, Teunissen, Charlotte, Wall, Anders E, Carter, Stephen F, Schöll, Michael, Choo, Il Han, Grimmer, Timo, Redolfi, Alberto, Nordberg, Agneta, Scheltens, Philip, Drzezga, Alexander, Frisoni, Giovanni B, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Jack, Clifford R, Jagust, William, Trojanowki, JQ, Toga, Arthur W, Beckett, Laurel, Green, Robert C, Gamst, Anthony, Saykin, Andrew J, Morris, John, Potter, William Z, Montine, Tom, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Bandy, Dan, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Cairns, Nigel J, Taylor-Reinwald, Lisa, Shaw, Les, Lee, Virginia M-Y, Korecka, Magdalena, Crawford, Karen, Neu, Scott, Harvey, Danielle, Kornak, John, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J, Molchan, Susan, Kaye, Jeffrey, Dolen, Sara, Quinn, Joseph, Schneider, Lon, Pawluczyk, Sonia, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Heidebrink, Judith L, Lord, Joanne L, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S, Bell, Karen L, Morris, John C, and Mintun, Mark A

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Aging, Alzheimer's Disease, Neurosciences, Brain Disorders, Acquired Cognitive Impairment, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, 2.1 Biological and endogenous factors, Aetiology, Neurological, Aged, Aged, 80 and over, Cognitive Dysfunction, Databases, Factual, Disease Progression, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neurodegenerative Diseases, Plaque, Amyloid, Predictive Value of Tests, Alzheimer's Disease Neuroimaging Initiative, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectivesThe aim of this study was to investigate predictors of progressive cognitive deterioration in patients with suspected non-Alzheimer disease pathology (SNAP) and mild cognitive impairment (MCI).MethodsWe measured markers of amyloid pathology (CSF β-amyloid 42) and neurodegeneration (hippocampal volume on MRI and cortical metabolism on [(18)F]-fluorodeoxyglucose-PET) in 201 patients with MCI clinically followed for up to 6 years to detect progressive cognitive deterioration. We categorized patients with MCI as A+/A- and N+/N- based on presence/absence of amyloid pathology and neurodegeneration. SNAPs were A-N+ cases.ResultsThe proportion of progressors was 11% (8/41), 34% (14/41), 56% (19/34), and 71% (60/85) in A-N-, A+N-, SNAP, and A+N+, respectively; the proportion of APOE ε4 carriers was 29%, 70%, 31%, and 71%, respectively, with the SNAP group featuring a significantly different proportion than both A+N- and A+N+ groups (p ≤ 0.005). Hypometabolism in SNAP patients was comparable to A+N+ patients (p = 0.154), while hippocampal atrophy was more severe in SNAP patients (p = 0.002). Compared with A-N-, SNAP and A+N+ patients had significant risk of progressive cognitive deterioration (hazard ratio = 2.7 and 3.8, p = 0.016 and p < 0.001), while A+N- patients did not (hazard ratio = 1.13, p = 0.771). In A+N- and A+N+ groups, none of the biomarkers predicted time to progression. In the SNAP group, lower time to progression was correlated with greater hypometabolism (r = 0.42, p = 0.073).ConclusionsOur findings support the notion that patients with SNAP MCI feature a specific risk progression profile.

Published
2015

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

Author

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

Published
2023
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21. Vascular burden and Alzheimer disease pathologic progression

Author

Lo, Raymond Y, Jagust, William 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, Liu, Enchi, Montine, Tom, Gamst, Anthony, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Harvey, Danielle, Kornak, John, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Bandy, Dan, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Cairns, Nigel J, Taylor-Reinwald, Lisa, Trojanowki, JQ, Shaw, Les, Lee, Virginia MY, Korecka, Magdalena, Crawford, Karen, Neu, Scott, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J, Molchan, Susan, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Dolen, Sara, Schneider, Lon S, Pawluczyk, Sonia, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Heidebrink, Judith L, Lord, Joanne L, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S, Bell, Karen L, Morris, John C, Ances, Beau, Carroll, Maria, Leon, Sue, Mintun, Mark A, Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Mitsis, Effie, Romirowsky, Aliza, deToledo-Morrell, Leyla, Shah, Raj C, Duara, Ranjan, and Varon, Daniel

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Aging, Biomedical Imaging, Dementia, Brain Disorders, Clinical Research, Vascular Cognitive Impairment/Dementia, Alzheimer's Disease, Neurosciences, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Neurological, Cardiovascular, Aged, Alzheimer Disease, Atrophy, Brain, Cognitive Dysfunction, Disease Progression, Female, Genotype, Humans, Leukoencephalopathies, Longitudinal Studies, Magnetic Resonance Imaging, Male, Positron-Emission Tomography, Alzheimer's Disease Neuroimaging Initiative, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveTo investigate the vascular contribution to longitudinal changes in Alzheimer disease (AD) biomarkers.MethodsThe Alzheimer's Disease Neuroimaging Initiative is a clinic based, longitudinal study with CSF, PET, and MRI biomarkers repeatedly measured in participants with normal cognition (NC), mild cognitive impairment (MCI), and mild AD. Participants with severe cerebrovascular risks were excluded. Cardiovascular risk scores and MRI white matter hyperintensities (WMHs) were treated as surrogate markers for vascular burden. Generalized estimating equations were applied, and both vascular burden and its interaction with time (vascular burden × time) or time-varying WMHs were entered into regression models to assess whether biomarker rates of change were modified by vascular burden.ResultsCardiovascular risk profiles were not predictive of progression in CSF β₄₂-amyloid, [¹⁸F]fluorodeoxyglucose (FDG) PET uptake, and MRI hippocampal atrophy. Greater baseline cardiovascular risks or WMHs were generally associated with cognitive impairment, particularly poor executive function. WMHs increased over time with a faster rate in MCI and AD than in NC. Increased time-varying WMH was associated with faster decline in executive function and lower FDG uptake in NC. Otherwise, WMH was not associated with CSF and MRI biomarkers in the 3 groups. These findings remained unchanged after accounting for APOE4.ConclusionIncreased WMHs are associated with aging, decreased glucose metabolism, and decline in executive function but do not affect AD-specific pathologic progression, suggesting that the vascular contribution to dementia is probably additive although not necessarily independent of the amyloid pathway.

Published
2012

22. Predicting missing biomarker data in a longitudinal study of Alzheimer disease

Author

Lo, Raymond Y., Jagust, William J., Aisen, Paul, Jack, Clifford R., Toga, Arthur W., Beckett, Laurel, Gamst, Anthony, Soares, Holly, C. Green, Robert, Montine, Tom, Thomas, Ronald G., Donohue, Michael, Walter, Sarah, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Bandy, Dan, Chen, Kewei, Morris, John, Lee, Virginia M.-Y., Korecka, Magdalena, Crawford, Karen, Neu, Scott, Harvey, Danielle, Kornak, John, Saykin, Andrew J., Foroud, Tatiana M., Potkin, Steven, Shen, Li, Buckholtz, Neil, Kaye, Jeffrey, Dolen, Sara, Quinn, Joseph, Schneider, Lon, Pawluczyk, Sonia, Spann, Bryan M., Brewer, James, Vanderswag, Helen, Heidebrink, Judith L., Lord, Joanne L., Petersen, Ronald, Johnson, Kris, Doody, Rachelle S., Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S., Bell, Karen L., Morris, John C., Mintun, Mark A., Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Tang, Cheuk, Marzloff, George, Toledo-Morrell, Leylade, Shah, Raj C., Duara, Ranjan, Varon, Daniel, Roberts, Peggy, Albert, Marilyn S., Pedroso, Julia, Toroney, Jaimie, Rusinek, Henry, de Leon, Mony J, De Santi, Susan M, Doraiswamy, P. Murali, Petrella, Jeffrey R., Aiello, Marilyn, Clark, Christopher M., Pham, Cassie, Nunez, Jessica, Smith, Charles D., Given, Curtis A., Hardy, Peter, Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Ismail, M. Saleem, Brand, Connie, Richard, Jennifer, Mulnard, Ruth A., Thai, Gaby, Mc-Adams-Ortiz, Catherine, Diaz-Arrastia, Ramon, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Anderson, Heather S., and Laubinger, Mary M.

Abstract

Objective:To investigate predictors of missing data in a longitudinal study of Alzheimer disease (AD).Methods:The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a clinic-based, multicenter, longitudinal study with blood, CSF, PET, and MRI scans repeatedly measured in 229 participants with normal cognition (NC), 397 with mild cognitive impairment (MCI), and 193 with mild AD during 2005–2007. We used univariate and multivariable logistic regression models to examine the associations between baseline demographic/clinical features and loss of biomarker follow-ups in ADNI.Results:CSF studies tended to recruit and retain patients with MCI with more AD-like features, including lower levels of baseline CSF Aβ42. Depression was the major predictor for MCI dropouts, while family history of AD kept more patients with AD enrolled in PET and MRI studies. Poor cognitive performance was associated with loss of follow-up in most biomarker studies, even among NC participants. The presence of vascular risk factors seemed more critical than cognitive function for predicting dropouts in AD.Conclusion:The missing data are not missing completely at random in ADNI and likely conditional on certain features in addition to cognitive function. Missing data predictors vary across biomarkers and even MCI and AD groups do not share the same missing data pattern. Understanding the missing data structure may help in the design of future longitudinal studies and clinical trials in AD.

Published
2012

23. Association of common genetic variants in GPCPD1 with scaling of visual cortical surface area in humans.

Author

Bakken, Trygve E, Roddey, J Cooper, Djurovic, Srdjan, Akshoomoff, Natacha, Amaral, David G, Bloss, Cinnamon S, Casey, B J, Chang, Linda, Ernst, Thomas M, Gruen, Jeffrey R, Jernigan, Terry L, Kaufmann, Walter E, Kenet, Tal, Kennedy, David N, Kuperman, Joshua M, Murray, Sarah S, Sowell, Elizabeth R, Rimol, Lars M, Mattingsdal, Morten, Melle, Ingrid, Agartz, Ingrid, Andreassen, Ole A, Schork, Nicholas J, Dale, Anders M, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Jack, Clifford R, Jr, Jagust, William, Trojanowki, John Q, Toga, Arthur W, Beckett, Laurel, Green, Robert C, Saykin, Andrew J, Morris, John, Liu, Enchi, Montine, Tom, Gamst, Anthony, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Harvey, Danielle, Kornak, John, Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Bandy, Dan, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Cairns, Nigel J, Taylor-Reinwald, Lisa, Trojanowki, J Q, Shaw, Les, Lee, Virginia M Y, Korecka, Magdalena, Crawford, Karen, Neu, Scott, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J, Molchan, Susan, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Dolen, Sara, Schneider, Lon S, Pawluczyk, Sonia, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Heidebrink, Judith L, Lord, Joanne L, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S, Bell, Karen L, Morris, John C, Ances, Beau, Carroll, Maria, Leon, Sue, Mintun, Mark A, Schneider, Stacy, Marson, Daniel, and Griffith, Randall

Subjects
Adolescent, Adult, Aged, Brain: pathology, Brain Mapping: methods, Cohort Studies, Diagnostic Imaging: methods, Female, Genetic Variation, Genome-Wide Association Study, Genomics, Genotype, Humans, Male, Middle Aged, Models, Genetic, Phosphoric Diester Hydrolases: genetics, Polymorphism, Single Nucleotide, Saccharomyces cerevisiae: metabolism, Visual Cortex: anatomy & histology, pathology
Abstract

Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the proportional surface area of visual cortex, we performed a genome-wide association study followed by replication in two independent cohorts. We identified one SNP (rs6116869) that replicated in both cohorts and had genome-wide significant association (P(combined) = 3.2 × 10(-8)). Furthermore, a metaanalysis of imputed SNPs in this genomic region identified a more significantly associated SNP (rs238295; P = 6.5 × 10(-9)) that was in strong linkage disequilibrium with rs6116869. These SNPs are located within 4 kb of the 5' UTR of GPCPD1, glycerophosphocholine phosphodiesterase GDE1 homolog (Saccharomyces cerevisiae), which in humans, is more highly expressed in occipital cortex compared with the remainder of cortex than 99.9% of genes genome-wide. Based on these findings, we conclude that this common genetic variation contributes to the proportional area of human visual cortex. We suggest that identifying genes that contribute to normal cortical architecture provides a first step to understanding genetic mechanisms that underlie visual perception.

Published
2012

24. Engaging adolescents in changing behaviour (EACH-B): a study protocol for a cluster randomised controlled trial to improve dietary quality and physical activity

Author

Strömmer, Sofia, Barrett, Millie, Woods-Townsend, Kathryn, Baird, Janis, Farrell, David, Lord, Joanne, Morrison, Leanne, Shaw, Sarah, Vogel, Christina, Lawrence, Wendy, Lovelock, Donna, Bagust, Lisa, Varkonyi-Sepp, Judit, Coakley, Patsy, Campbell, Lyall, Anderson, Ross, Horsfall, Tina, Kalita, Neelam, Onyimadu, Olu, Clarke, John, Cooper, Cyrus, Chase, Debbie, Lambrick, Danielle, Little, Paul, Hanson, Mark, Godfrey, Keith, Inskip, Hazel, and Barker, Mary

Published
2020
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25. Altering product placement to create a healthier layout in supermarkets: Outcomes on store sales, customer purchasing, and diet in a prospective matched controlled cluster study

Author

Vogel, Christina, Crozier, Sarah, Penn-Newman, Daniel, Ball, Kylie, Moon, Graham, Lord, Joanne, Cooper, Cyrus, and Baird, Janis

Subjects
Consumer behavior -- Health aspects, Store design -- Methods -- Health aspects -- Psychological aspects, Supermarkets -- Management -- Health aspects -- Design and construction -- Psychological aspects, Diet -- Health aspects -- Psychological aspects, Biological sciences
Abstract

Background Previous product placement trials in supermarkets are limited in scope and outcome data collected. This study assessed the effects on store-level sales, household-level purchasing, and dietary behaviours of a healthier supermarket layout. Methods and findings This is a prospective matched controlled cluster trial with 2 intervention components: (i) new fresh fruit and vegetable sections near store entrances (replacing smaller displays at the back) and frozen vegetables repositioned to the entrance aisle, plus (ii) the removal of confectionery from checkouts and aisle ends opposite. In this pilot study, the intervention was implemented for 6 months in 3 discount supermarkets in England. Three control stores were matched on store sales and customer profiles and neighbourhood deprivation. Women customers aged 18 to 45 years, with loyalty cards, were assigned to the intervention (n = 62) or control group (n = 88) of their primary store. The trial registration number is NCT03518151. Interrupted time series analysis showed that increases in store-level sales of fruits and vegetables were greater in intervention stores than predicted at 3 (1.71 standard deviations (SDs) (95% CI 0.45, 2.96), P = 0.01) and 6 months follow-up (2.42 SDs (0.22, 4.62), P = 0.03), equivalent to approximately 6,170 and approximately 9,820 extra portions per store, per week, respectively. The proportion of purchasing fruits and vegetables per week rose among intervention participants at 3 and 6 months compared to control participants (0.2% versus -3.0%, P = 0.22; 1.7% versus -3.5%, P = 0.05, respectively). Store sales of confectionery were lower in intervention stores than predicted at 3 (-1.05 SDs (-1.98, -0.12), P = 0.03) and 6 months (-1.37 SDs (-2.95, 0.22), P = 0.09), equivalent to approximately 1,359 and approximately 1,575 fewer portions per store, per week, respectively; no differences were observed for confectionery purchasing. Changes in dietary variables were predominantly in the expected direction for health benefit. Intervention implementation was not within control of the research team, and stores could not be randomised. It is a pilot study, and, therefore, not powered to detect an effect. Conclusions Healthier supermarket layouts can improve the nutrition profile of store sales and likely improve household purchasing and dietary quality. Placing fruits and vegetables near store entrances should be considered alongside policies to limit prominent placement of unhealthy foods. Trial registration ClinicalTrials.gov NCT03518151 (pre-results), Author(s): Christina Vogel 1,2,*, Sarah Crozier 1, Daniel Penn-Newman 1, Kylie Ball 3, Graham Moon 4, Joanne Lord 5, Cyrus Cooper 1,2, Janis Baird 1,2 1. Introduction Obesity and poor [...]

Published
2021
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28. Prognostic relevance of gait-related cognitive functions for dementia conversion in amnestic mild cognitive impairment

Author

Tuena, Cosimo, Maestri, Sara, Serino, Silvia, Pedroli, Elisa, Stramba-Badiale, Marco, Riva, Giuseppe, 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., Brewer, Jame, Fleisher, Adam, Vanderswag, Helen, Ziolkowski, Jaimie, Heidebrink, Judith L., Zbizek-Nulph, Lisa, Lord, Joanne L., Albers, Colleen S., Petersen, Ronald, Mason, Sara S., Knopman, David, Johnson, Kri, 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, Morris, John C., 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, Thoma, Shulman, Melanie, Faustin, Arline, Rao, Julia, Castro, Karen M., Ulysse, Anaztasia, Chen, Shannon, Doraiswamy, P. Murali, Petrella, Jeffrey R., 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., Khouli, Riham El, 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, 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 Dyck, Christopher H., Mecca, Adam P., Good, Susan P., Macavoy, Martha G., Carson, Richard E., Varma, Pradeep, Chertkow, Howard, Vaitekunas, Susan, Hosein, Chri, Black, Sandra, Stefanovic, Bojana, Heyn, Chri, Hsiung, Ging-Yuek Robin, 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., Weiner, Micheal W., Perry, David, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Mccann, Kelly, Poe, Jessica, Marshall, Gad A., Sperling, Reisa A., Johnson, Keith 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, Evaristu, Nadarajah, Sheeba, Lerner, Alan, Ogrocki, Paula, Tatsuoka, Curti, Fatica, Parianne, Fletcher, Evan, Maillard, Pauline, Olichney, John, Decarli, Charle, Carmichael, Owen, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Borrie, Michael, Lee, T. -Y., Bartha, 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., Ponto, Laura L. Bole, 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, Charle, 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, Null, Null, Serino, Silvia (ORCID:0000-0002-8422-1358), Riva, Giuseppe (ORCID:0000-0003-3657-106X), Tuena, Cosimo, Maestri, Sara, Serino, Silvia, Pedroli, Elisa, Stramba-Badiale, Marco, Riva, Giuseppe, 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., Brewer, Jame, Fleisher, Adam, Vanderswag, Helen, Ziolkowski, Jaimie, Heidebrink, Judith L., Zbizek-Nulph, Lisa, Lord, Joanne L., Albers, Colleen S., Petersen, Ronald, Mason, Sara S., Knopman, David, Johnson, Kri, 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, Morris, John C., 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, Thoma, Shulman, Melanie, Faustin, Arline, Rao, Julia, Castro, Karen M., Ulysse, Anaztasia, Chen, Shannon, Doraiswamy, P. Murali, Petrella, Jeffrey R., 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., Khouli, Riham El, 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, 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 Dyck, Christopher H., Mecca, Adam P., Good, Susan P., Macavoy, Martha G., Carson, Richard E., Varma, Pradeep, Chertkow, Howard, Vaitekunas, Susan, Hosein, Chri, Black, Sandra, Stefanovic, Bojana, Heyn, Chri, Hsiung, Ging-Yuek Robin, 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., Weiner, Micheal W., Perry, David, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Mccann, Kelly, Poe, Jessica, Marshall, Gad A., Sperling, Reisa A., Johnson, Keith 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, Evaristu, Nadarajah, Sheeba, Lerner, Alan, Ogrocki, Paula, Tatsuoka, Curti, Fatica, Parianne, Fletcher, Evan, Maillard, Pauline, Olichney, John, Decarli, Charle, Carmichael, Owen, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Borrie, Michael, Lee, T. -Y., Bartha, 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., Ponto, Laura L. Bole, 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, Charle, 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, Null, Null, Serino, Silvia (ORCID:0000-0002-8422-1358), and Riva, Giuseppe (ORCID:0000-0003-3657-106X)

Abstract

BackgroundIncreasing research suggests that gait abnormalities can be a risk factor for Alzheimer's Disease (AD). Notably, there is growing evidence highlighting this risk factor in individuals with amnestic Mild Cognitive Impairment (aMCI), however further studies are needed. The aim of this study is to analyze cognitive tests results and brain-related measures over time in aMCI and examine how the presence of gait abnormalities (neurological or orthopedic) or normal gait affects these trends. Additionally, we sought to assess the significance of gait and gait-related measures as prognostic indicators for the progression from aMCI to AD dementia, comparing those who converted to AD with those who remained with a stable aMCI diagnosis during the follow-up.MethodsFour hundred two individuals with aMCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included. Robust linear mixed-effects models were used to study the impact of gait abnormalities on a comprehensive neuropsychological battery over 36 months while controlling for relevant medical variables at baseline. The impact of gait on brain measures was also investigated. Lastly, the Cox proportional-hazards model was used to explore the prognostic relevance of abnormal gait and neuropsychological associated tests.ResultsWhile controlling for relevant covariates, we found that gait abnormalities led to a greater decline over time in attention (DSST) and global cognition (MMSE). Intriguingly, psychomotor speed (TMT-A) and divided attention (TMT-B) declined uniquely in the abnormal gait group. Conversely, specific AD global cognition tests (ADAS-13) and auditory-verbal memory (RAVLT immediate recall) declined over time independently of gait profile. All the other cognitive tests were not significantly affected by time or by gait profile. In addition, we found that ventricles size increased faster in the abnormal gait group compared to the normal gait group. In terms of prognosis, abnormal gai

Published
2023

30. Type 2 diabetes mellitus, brain atrophy, and cognitive decline

Author

Moran, Chris, Beare, Richard, Wang, Wei, Callisaya, Michele, Srikanth, Velandai, Weiner, Michael, Aisen, Paul, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Jack, Clifford R., Jr., Jagust, William, Trojanowki, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Saykin, Andrew J., Morris, John, Liu, Enchi, Green, Robert C., Montine, Tom, Petersen, Ronald, Aisen, Paul, Gamst, Anthony, Thomas, Ronald G., Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Beckett, Laurel, Harvey, Danielle, Gamst, Anthony, Donohue, Michael, Kornak, John, Jack, Clifford R., Jr., Dale, Anders, Bernstein, Matthew, Felmlee, Joel, Fox, Nick, Thompson, Paul, Schuff, Norbert, Alexander, Gene, DeCarli, Charles, Jagust, William, Bandy, Dan, Koeppe, Robert A., Foster, Norm, Reiman, Eric M., Chen, Kewei, Mathis, Chet, Morris, John, Cairns, Nigel J., Taylor-Reinwald, Lisa, Trojanowki, J.Q., Shaw, Les, Lee, Virginia M.Y., Korecka, Magdalena, Toga, Arthur W., Crawford, Karen, Neu, Scott, Saykin, Andrew J., Foroud, Tatiana M., Potkin, Steven, Shen, Li, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J., Molchan, Susan, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Dolen, Sara, Schneider, Lon S., Pawluczyk, Sonia, Spann, Bryan M., Brewer, James, Vanderswag, Helen, Heidebrink, Judith L., Lord, Joanne L., Petersen, Ronald, Johnson, Kris, Doody, Rachelle S., Villanueva-Meyer, Javier, Chowdhury, Munir, Stern, Yaakov, Honig, Lawrence S., Bell, Karen L., Morris, John C., Ances, Beau, Carroll, Maria, Leon, Sue, Mintun, Mark A., Schneider, Stacy, Marson, Daniel, Griffith, Randall, Clark, David, Grossman, Hillel, Mitsis, Effie, Romirowsky, Aliza, deToledo-Morrell, Leyla, Shah, Raj C., Duara, Ranjan, Varon, Daniel, Roberts, Peggy, Albert, Marilyn, Onyike, Chiadi, Kielb, Stephanie, Rusinek, Henry, de Leon, Mony J, Glodzik, Lidia, De Santi, Susan, Doraiswamy, P. Murali, Petrella, Jeffrey R., Coleman, R. Edward, Arnold, Steven E., Karlawish, Jason H., Wolk, David, Smith, Charles D., Jicha, Greg, Hardy, Peter, 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, McAdams-Ortiz, Catherine, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Diaz-Arrastia, Ramon, King, Richard, Weiner, Myron, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Anderson, Heather S., Swerdlow, Russell H., Apostolova, Liana, Lu, Po H., Bartzokis, George, Silverman, Daniel H.S., Graff-Radford, Neill R, Parfitt, Francine, Johnson, Heather, Farlow, Martin R., Hake, Ann Marie, Matthews, Brandy R., Herring, Scott, 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, Kristina, 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, Belden, Christine, Jacobson, Sandra, Kowall, Neil, Killiany, Ronald, Budson, Andrew E., Norbash, Alexander, Johnson, Patricia Lynn, Obisesan, Thomas O., Wolday, Saba, Bwayo, Salome K., Lerner, Alan, Hudson, Leon, Ogrocki, Paula, Fletcher, Evan, Carmichael, Owen, Olichney, John, DeCarli, Charles, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Dr Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Potkin, Steven G., Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Fleisher, Adam, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W., Kataki, Maria, Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Saykin, Andrew J., Santulli, Robert B., 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, Longmire, Crystal Flynn, Spicer, Kenneth, Finger, Elizabether, Rachinsky, Irina, Rogers, John, Kertesz, Andrew, 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, and Raj, Balebail Ashok

Published
2019
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32. 18F-florbetapir Positron Emission Tomography–determined Cerebral β-Amyloid Deposition and Neurocognitive Performance after Cardiac Surgery

Author

Klinger, Rebecca Y., James, Olga G., Borges-Neto, Salvador, Bisanar, Tiffany, Li, Yi-Ju, Qi, Wenjing, Berger, Miles, Terrando, Niccolò, Newman, Mark F., Doraiswamy, P. Murali, Mathew, Joseph P., Weiner, Michael W., Aisen, Paul, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Jack, Clifford R., Jr., Jagust, William, Trojanowki, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Saykin, Andrew J., Morris, John, Shaw, Leslie M., Khachaturian, Zaven, Sorensen, Greg, Carrillo, Maria, Kuller, Lew, Raichle, Marc, Paul, Steven, Davies, Peter, Fillit, Howard, Hefti, Franz, Holtzman, David, Mesulam, M. Marcel, Potter, William, Snyder, Peter, Schwartz, Adam, Green, Robert C., Montine, Tom, Petersen, Ronald, Aisen, Paul, Thomas, Ronald G., Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Jiminez, Gus, Balasubramanian, Archana B., Mason, Jennifer, Sim, Iris, Beckett, Laurel, Harvey, Danielle, Donohue, Michael, Jack, Clifford R., Jr., Bernstein, Matthew, Fox, Nick, Thompson, Paul, Schuff, Norbert, DeCArli, Charles, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Vemuri, Prashanthi, Jones, David, Kantarci, Kejal, Ward, Chad, Jagust, William, Koeppe, Robert A., Foster, Norm, Reiman, Eric M., Chen, Kewei, Mathis, Chet, Landau, Susan, Morris, John C., Cairns, Louis Nigel J., Franklin, Erin, Taylor-Reinwald, Lisa, Shaw, Leslie M., Trojanowki, John Q., Lee, Virginia, Korecka, Magdalena, Figurski, Michal, Toga, Arthur W., Crawford, Karen, Neu, Scott, Saykin, Andrew J., Foroud, Tatiana M., Potkin, Steven, Shen, Li, Faber, Kelley, Kim, Sungeun, Nho, Kwangsik, Weiner, Michael W., Thal, Lean, Khachaturian, Zaven, Thal, Leon, Buckholtz, Neil, Weiner, Michael W., Snyder, Peter J., Potter, William, Paul, Steven, Albert, Marilyn, Frank, Richard, Khachaturian, Zaven, Hsiao, John, Kaye, Jeffrey, Quinn, Joseph, Silbert, Lisa, Lind, Betty, Carter, Raina, Dolen, Sara, Schneider, Lon S., Pawluczyk, Sonia, Becerra, Mauricio, Teodoro, Liberty, Spann, Bryan M., Brewer, James, Vanderswag, Helen, Fleisher, Adam, Heidebrink, Judith L., Lord, Joanne L., Petersen, Ronald, Mason, Sara S., Albers, Colleen S., Knopman, David, Johnson, Kris, Doody, Rachelle S., Villanueva-Meyer, Javier, Pavlik, Valory, Shibley, Victoria, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S., Bell, Karen L., Ances, Beau, Morris, John C., Carroll, Maria, Creech, Mary L., Franklin, Erin, Mintun, Mark A., Schneider, Stacy, Oliver, Angela, Marson, Daniel, Geldmacher, David, Love, Marissa Natelson, Griffith, Randall, Clark, David, Brockington, John, Roberson, Erik, Grossman, Hillel, Mitsis, Effie, Shah, Raj C., deToledo-Morrell, Leyla, Duara, Ranjan, Greig-Custo, Maria T., Barker, Warren, Albert, Marilyn, Onyike, Chiadi, D’Agostino, Daniel, II, Kielb, Stephanie, Sadowski, Martin, Sheikh, Mohammed O., Ulysse, Anaztasia, Gaikwad, Mrunalini, Petrella, Jeffrey R., Wong, Terence Z., Coleman, Edward, Arnold, Steven E., Karlawish, Jason H., Wolk, David A., Clark, Christopher M., 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, Potkin, Steven G., Preda, Adrian, Nguyen, Dana, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Swerdlow, Russell H., Brooks, William M., Apostolova, Liana, Tingus, Kathleen, Woo, Ellen, Silverman, Daniel H.S., Lu, Po H., Bartzokis, George, Graff-Radford, Neill R, Parfitt, Francine, Poki-Walker, Kim, Farlow, Martin R., Hake, Ann Marie, Matthews, Brandy R., Brosch, Jared R., Herring, Scott, van Dyck, Christopher H., Carson, Richard E., MacAvoy, Martha G., Varma, Pradeep, Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Ging-Yuek, Hsiung, Robin, Mudge, Benita, Sossi, Vesna, Feldman, Howard, Assaly, Michele, Finger, Elizabeth, Pasternack, Stephen, Rachisky, Irina, Trost, Dick, Kertesz, Andrew, Bernick, Charles, Munic, Donna, Mesulam, Marek-Marsel, Rogalski, Emily, Lipowski, Kristine, Weintraub, Sandra, Bonakdarpour, Borna, Kerwin, Diana, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A., Johnson, Keith A., Marshall, Gad, 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, Tatsuoka, Curtis, Fatica, Parianne, Fletcher, Evan, Maillard, Pauline, Olichney, John, DeCarli, Charles, Carmichael, Owen, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Dr Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Potkin, Steven G., Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Burke, Anna, Milliken, Ann Marie, Trncic, Nadira, Fleisher, Adam, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W., Kataki, Maria, Kelley, Brendan, Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Flashman, Laura A., Seltzer, Marc, Hynes, Mary L., Santulli, Robert B., Sink, Kaycee M., Gordineer, Leslie, Williamson, Jeff D., Garg, Pradeep, Watkins, Franklin, Ott, Brian R., Tremont, Geoffrey, Daiello, Lori A., Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J., Miller, Bruce L., Perry, David, Mintzer, Jacobo, Spicer, Kenneth, Bachman, David, Finger, Elizabeth, Pasternak, Stephen, Rachinsky, Irina, Rogers, John, Kertesz, Andrew, Drost, Dick, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K., Smith, Karen Ekstam, Koleva, Hristina, Nam, Ki Won, Shim, Hyungsub, Relkin, Norman, Chiang, Gloria, Lin, Michael, Ravdin, Lisa, Smith, Amanda, Ashok Raj, Balebail, Fargher, Kristin, Weiner, Michael W., Aisen, Paul, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Green, Robert C., Harvey, Danielle, Jack, Clifford R., Jr., Jagust, William, Morris, John C., Saykin, Andrew J., Shaw, Leslie M., Toga, Arthur W., Trojanowki, John Q., Neylan, Thomas, Grafman, Jordan, Grafman, Jordan, Green, Robert C., Montine, Tom, Weiner, Michael, Petersen, Ronald, Aisen, Paul, Thomas, Ronald G., Donohue, Michael, Gessert, Devon, Sather, Tamie, Davis, Melissa, Morrison, Rosemary, Jiminez, Gus, Neylan, Thomas, Hayes, Jacqueline, Finely, Shannon, Harvey, Danielle, Donohue, Michael, Jack, Clifford R., Jr., Bernstein, Matthew, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Kantarci, Kejal, Ward, Chad, Jagust, William, Koeppe, Robert A., Foster, Norm, Reiman, Eric M., Chen, Kewei, Landau, Susan, Morris, John C., Cairns, Nigel J., Householder, Erin, Shaw, Leslie M., Trojanowki, John Q., Lee, Virginia, Korecka, Magdalena, Figurski, Michal, Toga, Arthur W., Crawford, Karen, Neu, Scott, Saykin, Andrew J., Foroud, Tatiana M., Potkin, Steven, Shen, Li, Faber, Kelley, Kim, Sungeun, Nho, Kwangsik, Weiner, Michael W., Friedl, Karl, Schneider, Lon S., Pawluczyk, Sonia, Becerra, Mauricio, Brewer, James, Vanderswag, Helen, Stern, Yaakov, Honig, Lawrence S., Bell, Karen L., Fleischman, Debra, Arfanakis, Konstantinos, Shah, Raj C., Duara, Ranjan, Varon, Daniel, Greig, Maria T, Petrella, Jeffrey R., Porsteinsson, Anton P., Goldstein, Bonnie, Martin, Kimberly S., Potkin, Steven G., Preda, Adrian, Nguyen, Dana, Mintzer, Jacobo, Massoglia, Dino, Brawman-Mintzer, Olga, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Jagust, William, Landau, Susan, Rosen, Howard, Perry, David, Turner, Raymond Scott, Behan, Kelly, Reynolds, Brigid, Sperling, Reisa A., Johnson, Keith A., Marshall, Gad, Sabbagh, Marwan N., Jacobson, Sandra A., Sirrel, Sherye A., Obisesan, Thomas O., Wolday, Saba, Allard, Joanne, Johnson, Sterling C., Fruehling, J. Jay, Harding, Sandra, Peskind, Elaine R., Petrie, Eric C., Li, Gail, Yesavage, Jerome A., Taylor, Joy L., Furst, Ansgar J., Chao, Steven, Relkin, Norman, Chiang, Gloria, Ravdin, Lisa, Blumenthal, James A., Karhausen, Jorn A., Kertai, Miklos D., Podgoreanu, Mihai V., Stafford-Smith, Mark, Swaminathan, Madhav, Warner, David S., Funk, Bonita L., Balajonda, Narai, Brassard, Rachele, Cooter, Mary, Toulgoat-Dubois, Yanne, Waweru, Peter, Babyak, Michael A., Blumenthal, James A., Browndyke, Jeffrey N., Welsh-Bohmer, Kathleen A., Sketch, Michael H., Jr., Bennett, Ellen R., Graffagnino, Carmelo, Laskowitz, Daniel T., Strittmatter, Warren J., Collins, Kevin, Smigla, Greg, Shearer, Ian, D’Amico, Thomas A., Daneshmand, Mani A., Gaca, R. Jeffrey G., Glower, Donald D., Haney, Jack, Harpole, R. David, Hartwig, Mathew G., Hughes, G. Chad, Klapper, Jacob A., Lin, Shu S., Lodge, Andrew J., Milano, Carmelo A., Plichta, Ryan P., Schroeder, Jacob N., Smith, Peter K., and Tong, Betty C.

Published
2018
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33. CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial

Author

Fennell, Dean A., Kirkpatrick, Emma, Cozens, Kelly, Nye, Mavis, Lester, Jason, Hanna, Gerard, Steele, Nicola, Szlosarek, Peter, Danson, Sarah, Lord, Joanne, Ottensmeier, Christian, Barnes, Daniel, Hill, Stephanie, Kalevras, Mihalis, Maishman, Tom, and Griffiths, Gareth

Published
2018
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34. Catheter Ablation versus Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation (CASA-AF): study protocol for a randomised controlled trial

Author

Khan, Habib Rehman, Kralj-Hans, Ines, Haldar, Shouvik, Bahrami, Toufan, Clague, Jonathan, De Souza, Anthony, Francis, Darrel, Hussain, Wajid, Jarman, Julian, Jones, David Gareth, Mediratta, Neeraj, Mohiaddin, Raad, Salukhe, Tushar, Jones, Simon, Lord, Joanne, Murphy, Caroline, Kelly, Joanna, Markides, Vias, Gupta, Dhiraj, and Wong, Tom

Published
2018
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35. Cemiplimab for treating cutaneous squamous cell carcinoma (CDF review TA592)

Author

Kalita, Neelam, Woods, Lois, Lord, Joanne, and Frampton, Geoff

Abstract

This report is a critique of the company’s submission (CS) to the NICE Cancer Drugs Fund (CDF) review of TA592 on the clinical effectiveness and cost effectiveness of cemiplimab for treating cutaneous squamous cell carcinoma.

Published
2022

39. LB-469804-02 LONG-TERM OUTCOMES IN LONG STANDING PERSISTENT ATRIAL FIBRILLATION FOLLOWING CATHETER OR THORACOSCOPIC SURGICAL ABLATION USING CONTINUOUS MONITORING: 3-YEAR FOLLOW-UP OF THE CASA-AF RANDOMISED CONTROLLED TRIAL

Author

Boyalla, Vennela, Haldar, Shouvik, Khan, Habib, Kralj-Hans, Ines, Banya, Winston, Lord, Joanne, Gnanasekar, Anitha, Bahrami, Toufan, Desouza, Anthony, Clague, Jonathan, Francis, Darrel P., Hussain, Wajid, Jarman, Julian W., Jones, David G., Chen, Zhong, Mediratta, Neeraj, Hyde, Jonathan, Lewis, Michael, Mohiaddin, Raad, Salukhe, Tushar, Khattar, Rajdeep, Markides, Vias, McCready, James, Gupta, Dhiraj, and Wong, Tom

Published
2024
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40. Glucose metabolism patterns: A potential index to characterize brain ageing and predict high conversion risk into cognitive impairment

Author

Jiang, Jiehui, Sheng, Can, Aisen, Paul, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S, Bell, Karen L, Ances, Beau, Carroll, Maria, Leon, Sue, Mintun, Mark A, Schneider, Stacy, Oliver, Angela, Petersen, Ronald, Marson, Daniel, Griffith, Randall, Clark, David, Geldmacher, David, Brockington, John, Roberson, Erik, Grossman, Hillel, Mitsis, Effie, de Toledo-Morrell, Leyla, Shah, Raj C, Jack, Clifford R, Duara, Ranjan, Varon, Daniel, Greig, Maria T, Roberts, Peggy, Onyike, Chiadi, D'Agostino, Daniel, Kielb, Stephanie, Galvin, James E, Cerbone, Brittany, Michel, Christina A, Jagust, William, Rusinek, Henry, de Leon, Mony J, Glodzik, Lidia, De Santi, Susan, Murali Doraiswamy, P., Petrella, Jeffrey R, Wong, Terence Z, Arnold, Steven E, Karlawish, Jason H, Wolk, David, Trojanowski, John Q, Smith, Charles D, Jicha, Greg, Hardy, Peter, Sinha, Partha, Oates, Elizabeth, Conrad, Gary, Lopez, Oscar L, Oakley, MaryAnn, Simpson, Donna M, Porsteinsson, Anton P, Toga, Arthur W, Goldstein, Bonnie S, Martin, Kim, Makino, Kelly M, Saleem Ismail, M., Brand, Connie, Mulnard, Ruth A, Thai, Gaby, McAdams-Ortiz, Catherine, Womack, Kyle, Mathews, Dana, Beckett, Laurel, Quiceno, Mary, Diaz-Arrastia, Ramon, King, Richard, Weiner, Myron, Martin-Cook, Kristen, DeVous, Michael, I Levey, Allan, Lah, James J, Cellar, Janet S, Burns, Jeffrey M, Green, Robert C, 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, Saykin, Andrew J, Kendall, Tracy, Johnson, Heather, Farlow, Martin R, Hake, Ann Marie, Matthews, Brandy R, Herring, Scott, Hunt, Cynthia, van Dyck, Christopher H, Carson, Richard E, MacAvoy, Martha G, Morris, John, Chertkow, Howard, Bergman, Howard, Hosein, Chris, Robin Hsiung, Ging-Yuek, Feldman, Howard, Mudge, Benita, Assaly, Michele, Bernick, Charles, Munic, Donna, Kertesz, Andrew, Chen, Guanqun, Shaw, Leslie, Rogers, John, Trost, Dick, Kerwin, Diana, Lipowski, Kristine, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Khachaturian, Zaven, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A, Johnson, Keith A, Marshall, Gad, Frey, Meghan, Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan N, Sorensen, Greg, Belden, Christine M, Jacobson, Sandra A, Sirrel, Sherye A, Kowall, Neil, Killiany, Ronald, Budson, Andrew E, Norbash, Alexander, Johnson, Patricia Lynn, Allard, Joanne, Lerner, Alan, Kuller, Lew, Ogrocki, Paula, Hudson, Leon, Fletcher, Evan, Carmichae, Owen, Olichney, John, DeCarli, Charles, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Rob, Raichle, Marcus, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M, Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Paul, Steven, 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, Davies, Peter, 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, Fillit, Howard, Malloy, Paul, Correia, Stephen, Rosen, Howard J, Miller, Bruce L, Mintzer, Jacobo, Spicer, Kenneth, Bachman, David, Pasternak, Stephen, Rachinsky, Irina, Drost, Dick, Hefti, Franz, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K, Ponto, Laura L Boles, Shim, Hyungsub, Elizabeth Smith, Karen, Relkin, Norman, Chaing, Gloria, Raudin, Lisa, Holtzman, David, Smith, Amanda, Fargher, Kristin, Raj, Balebail Ashok, Neylan, Thomas, Grafman, Jordan, Davis, Melissa, Morrison, Rosemary, Hayes, Jacqueline, Finley, Shannon, Friedl, Karl, Liu, Chunhua, Mesulam, Marek M, Fleischman, Debra, Arfanakis, Konstantinos, James, Olga, Massoglia, Dino, Jay Fruehling, J., Harding, Sandra, Peskind, Elaine R, Petrie, Eric C, Li, Gail, Yesavage, Jerome A, Potter, William, Taylor, Joy L, Furst, Ansgar J, Snyder, Peter, Schwartz, Adam, Montine, Tom, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Jin, Shichen, Jiminez, Gus, Harvey, Danielle, Bernstein, Matthew, Thompson, Paul, Schuff, Norbert, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Vemuri, Prashanthi, Jones, David, Li, Lanlan, Kantarci, Kejal, Ward, Chad, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Landau, Susan, Cairns, Nigel J, Householder, Erin, Jiang, Xueyan, Taylor-Reinwald, Lisa, Lee, Virginia, Korecka, Magdalena, Figurski, Michal, Crawford, Karen, Neu, Scott, Foroud, Tatiana M, Potkin, Steven G, Shen, Li, Faber, Kelley, Han, Ying, Kim, Sungeun, Nho, Kwangsik, Thal, Leon, Buckholtz, Neil, Albert, Marylyn, Frank, Richard, Hsiao, John, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Initiative, Alzheimer’s Disease Neuroimaging, Carter, Raina, Dolen, Sara, Schneider, Lon S, Pawluczyk, Sonia, Beccera, Mauricio, Teodoro, Liberty, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Fleisher, Adam, Weiner, Michael W, Heidebrink, Judith L, Lord, Joanne L, Mason, Sara S, Albers, Colleen S, Knopman, David S, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, and Rountree, Susan

Subjects
Glucose metabolism, Positron emission tomography, Aging, Pattern, Brain, Glucose, Brain ageing, Alzheimer Disease, Fluorodeoxyglucose F18, Positron-Emission Tomography, Humans, Original Article, Cognitive Dysfunction, ddc:610, Geriatrics and Gerontology, Aged
Abstract

Exploring individual hallmarks of brain ageing is important. Here, we propose the age-related glucose metabolism pattern (ARGMP) as a potential index to characterize brain ageing in cognitively normal (CN) elderly people. We collected (18)F-fluorodeoxyglucose ((18)F-FDG) PET brain images from two independent cohorts: the Alzheimer’s Disease Neuroimaging Initiative (ADNI, N = 127) and the Xuanwu Hospital of Capital Medical University, Beijing, China (N = 84). During follow-up (mean 80.60 months), 23 participants in the ADNI cohort converted to cognitive impairment. ARGMPs were identified using the scaled subprofile model/principal component analysis method, and cross-validations were conducted in both independent cohorts. A survival analysis was further conducted to calculate the predictive effect of conversion risk by using ARGMPs. The results showed that ARGMPs were characterized by hypometabolism with increasing age primarily in the bilateral medial superior frontal gyrus, anterior cingulate and paracingulate gyri, caudate nucleus, and left supplementary motor area and hypermetabolism in part of the left inferior cerebellum. The expression network scores of ARGMPs were significantly associated with chronological age (R = 0.808, p

Published
2022

42. Additional file 4 of Aspirin to target arterial events in chronic kidney disease (ATTACK): study protocol for a multicentre, prospective, randomised, open-label, blinded endpoint, parallel group trial of low-dose aspirin vs. standard care for the primary prevention of cardiovascular disease in people with chronic kidney disease

Author

Gallagher, Hugh, Dumbleton, Jennifer, Maishman, Tom, Whitehead, Amy, Moore, Michael V., Fuat, Ahmet, Fitzmaurice, David, Henderson, Robert A., Lord, Joanne, Griffith, Kathryn E., Stevens, Paul, Taal, Maarten W., Stevenson, Diane, Fraser, Simon D., Lown, Mark, Hawkey, Christopher J., and Roderick, Paul J.

Subjects
TheoryofComputation_ANALYSISOFALGORITHMSANDPROBLEMCOMPLEXITY, ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS, MathematicsofComputing_NUMERICALANALYSIS, Data_FILES, MathematicsofComputing_DISCRETEMATHEMATICS
Abstract

Additional file 4. Endpoint definitions.

Published
2022
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43. Additional file 2 of Aspirin to target arterial events in chronic kidney disease (ATTACK): study protocol for a multicentre, prospective, randomised, open-label, blinded endpoint, parallel group trial of low-dose aspirin vs. standard care for the primary prevention of cardiovascular disease in people with chronic kidney disease

Author

Gallagher, Hugh, Dumbleton, Jennifer, Maishman, Tom, Whitehead, Amy, Moore, Michael V., Fuat, Ahmet, Fitzmaurice, David, Henderson, Robert A., Lord, Joanne, Griffith, Kathryn E., Stevens, Paul, Taal, Maarten W., Stevenson, Diane, Fraser, Simon D., Lown, Mark, Hawkey, Christopher J., and Roderick, Paul J.

Abstract

Additional file 2. Informed Consent Form.

Published
2022
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44. Additional file 5 of Aspirin to target arterial events in chronic kidney disease (ATTACK): study protocol for a multicentre, prospective, randomised, open-label, blinded endpoint, parallel group trial of low-dose aspirin vs. standard care for the primary prevention of cardiovascular disease in people with chronic kidney disease

Author

Gallagher, Hugh, Dumbleton, Jennifer, Maishman, Tom, Whitehead, Amy, Moore, Michael V., Fuat, Ahmet, Fitzmaurice, David, Henderson, Robert A., Lord, Joanne, Griffith, Kathryn E., Stevens, Paul, Taal, Maarten W., Stevenson, Diane, Fraser, Simon D., Lown, Mark, Hawkey, Christopher J., and Roderick, Paul J.

Abstract

Additional file 5. SPIRIT checklist.

Published
2022
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45. Additional file 3 of Aspirin to target arterial events in chronic kidney disease (ATTACK): study protocol for a multicentre, prospective, randomised, open-label, blinded endpoint, parallel group trial of low-dose aspirin vs. standard care for the primary prevention of cardiovascular disease in people with chronic kidney disease

Author

Gallagher, Hugh, Dumbleton, Jennifer, Maishman, Tom, Whitehead, Amy, Moore, Michael V., Fuat, Ahmet, Fitzmaurice, David, Henderson, Robert A., Lord, Joanne, Griffith, Kathryn E., Stevens, Paul, Taal, Maarten W., Stevenson, Diane, Fraser, Simon D., Lown, Mark, Hawkey, Christopher J., and Roderick, Paul J.

Subjects
Hardware_GENERAL, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Data_FILES
Abstract

Additional file 3. Participant Information Sheet.

Published
2022
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46. Additional file 1 of Aspirin to target arterial events in chronic kidney disease (ATTACK): study protocol for a multicentre, prospective, randomised, open-label, blinded endpoint, parallel group trial of low-dose aspirin vs. standard care for the primary prevention of cardiovascular disease in people with chronic kidney disease

Author

Gallagher, Hugh, Dumbleton, Jennifer, Maishman, Tom, Whitehead, Amy, Moore, Michael V., Fuat, Ahmet, Fitzmaurice, David, Henderson, Robert A., Lord, Joanne, Griffith, Kathryn E., Stevens, Paul, Taal, Maarten W., Stevenson, Diane, Fraser, Simon D., Lown, Mark, Hawkey, Christopher J., and Roderick, Paul J.

Subjects
ComputingMethodologies_PATTERNRECOGNITION, Data_MISCELLANEOUS, Data_FILES
Abstract

Additional file 1. WHO dataset.

Published
2022
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