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1. Genetic associations with dementia‐related proteinopathy: Application of item response theory

Author

Katsumata, Yuriko, Fardo, David W, Shade, Lincoln MP, Wu, Xian, Karanth, Shama D, Hohman, Timothy J, Schneider, Julie A, Bennett, David A, Farfel, Jose M, Gauthreaux, Kathryn, Mock, Charles, Kukull, Walter A, Abner, Erin L, Nelson, Peter T, Carrillo, Maria, Reiman, Eric M, Chen, Kewei, Masterman, Donna, Green, Robert C, Ho, Carole, Fleisher, Adam, Saykin, Andrew J, Nho, Kwangsik, Apostolova, Liana G, Risacher, Shannon L, Jackson, Jonathan, Forghanian-Arani, Arvin, Borowski, Bret, Ward, Chad, Schwarz, Christopher, Jack, Clifford R, Jones, David, Gunter, Jeff, Kantarci, Kejal, Senjem, Matthew, Vemuri, Prashanthi, Reid, Robert, Petersen, Ronald, Hsiao, John K, Potter, William, Masliah, Eliezer, Ryan, Laurie, Bernard, Marie, Silverberg, Nina, Kormos, Adrienne, Conti, Cat, Veitch, Dallas, Flenniken, Derek, Sacrey, Diana Truran, Choe, Mark, Ashford, Miriam, Chen, Stephanie Rossi, Faber, Kelley, Nudelman, Kelly, Wilme, Kristi, Foroud, Tatiana M, Trojanowki, John Q, Shaw, Leslie M, Korecka, Magdalena, Figurski, Michal, Khachaturian, Zaven, Barnes, Lisa, Malone, Ian, Fox, Nick C, Beckett, Laurel, Weiner, Michael W, Jagust, William, Landau, Susan, Knaack, Alexander, DeCarli, Charles, Harvey, Danielle, Fletcher, Evan, González, Hector, Jin, Chengshi, Tosun‐Turgut, Duygu, Neuhaus, John, Fockler, Juliet, Nosheny, Rachel, Koeppe, Robert A, Yushkevich, Paul A, Das, Sandhitsu, Mathis, Chet, Toga, Arthur W, Zimmerman, Caileigh, Gessert, Devon, Shcrer, Elizabeth, Miller, Garrett, Coker, Godfrey, Jimenez, Gustavo, Salazar, Jennifer, Pizzola, Jeremy, Crawford, Karen, Hergesheimer, Lindsey, Donohue, Michael, and Rafii, Michael

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Acquired Cognitive Impairment, Neurodegenerative, Brain Disorders, Dementia, Genetics, Prevention, Aging, 2.1 Biological and endogenous factors, Aetiology, Neurological, Humans, alpha-Synuclein, TDP-43 Proteinopathies, Proteostasis Deficiencies, DNA-Binding Proteins, Biological Products, Alzheimer Disease, Membrane Proteins, Nerve Tissue Proteins, Alzheimer's Disease Neuroimaging Initiative, National Alzheimer's Coordinating Center, ARHGEF28, Alzheimer's Coordinating Center, Alzheimer's Disease Sequencing Project, Alzheimer's disease neuropathologic changes, Item response theory, Lewy, RGNEF, Religious Orders Study, Rush Memory and Aging Project, SDHAF1, TMEM68, neuropathology, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionAlthough dementia-related proteinopathy has a strong negative impact on public health, and is highly heritable, understanding of the related genetic architecture is incomplete.MethodsWe applied multidimensional generalized partial credit modeling (GPCM) to test genetic associations with dementia-related proteinopathies. Data were analyzed to identify candidate single nucleotide variants for the following proteinopathies: Aβ, tau, α-synuclein, and TDP-43.ResultsFinal included data comprised 966 participants with neuropathologic and WGS data. Three continuous latent outcomes were constructed, corresponding to TDP-43-, Aβ/Tau-, and α-synuclein-related neuropathology endophenotype scores. This approach helped validate known genotype/phenotype associations: for example, TMEM106B and GRN were risk alleles for TDP-43 pathology; and GBA for α-synuclein/Lewy bodies. Novel suggestive proteinopathy-linked alleles were also discovered, including several (SDHAF1, TMEM68, and ARHGEF28) with colocalization analyses and/or high degrees of biologic credibility.DiscussionA novel methodology using GPCM enabled insights into gene candidates for driving misfolded proteinopathies.HighlightsLatent factor scores for proteinopathies were estimated using a generalized partial credit model. The three latent continuous scores corresponded well with proteinopathy severity. Novel genes associated with proteinopathies were identified. Several genes had high degrees of biologic credibility for dementia risk factors.

Published
2024

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

Author

Jo, Taeho, Kim, Junpyo, Bice, Paula, Huynh, Kevin, Wang, Tingting, Arnold, Matthias, Meikle, Peter J, Giles, Corey, Kaddurah-Daouk, Rima, Saykin, Andrew J, Nho, Kwangsik, 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, Risacher, Shannon L, Kastenmüller, Gabi, 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, 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, and Ryan, Laurie

Subjects
Medical Biochemistry and Metabolomics, Biomedical and Clinical Sciences, Neurosciences, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Networking and Information Technology R&D (NITRD), Machine Learning and Artificial Intelligence, Dementia, Aging, Brain Disorders, Alzheimer's Disease, Neurodegenerative, Neurological, Humans, Aged, Magnetic Resonance Imaging, Deep Learning, Alzheimer Disease, Neuroimaging, Metabolome, Lipids, Cognitive Dysfunction, Alzheimer's Disease Metabolomics Consortium, Alzheimer's Disease Neuroimaging Initiative, Alzheimer's disease, Deep learning, Lipidomics, Machine learning, Metabolomics, Clinical Sciences, Public Health and Health Services, Clinical sciences, Epidemiology
Abstract

BackgroundDeep learning has shown potential in various scientific domains but faces challenges when applied to complex, high-dimensional multi-omics data. Alzheimer's Disease (AD) is a neurodegenerative disorder that lacks targeted therapeutic options. This study introduces the Circular-Sliding Window Association Test (c-SWAT) to improve the classification accuracy in predicting AD using serum-based metabolomics data, specifically lipidomics.MethodsThe c-SWAT methodology builds upon the existing Sliding Window Association Test (SWAT) and utilizes a three-step approach: feature correlation analysis, feature selection, and classification. Data from 997 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) served as the basis for model training and validation. Feature correlations were analyzed using Weighted Gene Co-expression Network Analysis (WGCNA), and Convolutional Neural Networks (CNN) were employed for feature selection. Random Forest was used for the final classification.FindingsThe application of c-SWAT resulted in a classification accuracy of up to 80.8% and an AUC of 0.808 for distinguishing AD from cognitively normal older adults. This marks a 9.4% improvement in accuracy and a 0.169 increase in AUC compared to methods without c-SWAT. These results were statistically significant, with a p-value of 1.04 × 10ˆ-4. The approach also identified key lipids associated with AD, such as Cer(d16:1/22:0) and PI(37:6).InterpretationOur results indicate that c-SWAT is effective in improving classification accuracy and in identifying potential lipid biomarkers for AD. These identified lipids offer new avenues for understanding AD and warrant further investigation.FundingThe specific funding of this article is provided in the acknowledgements section.

Published
2023

3. Determinants of cognitive and brain resilience to tau pathology: a longitudinal analysis

Author

Bocancea, Diana I, Svenningsson, Anna L, van Loenhoud, Anna C, Groot, Colin, Barkhof, Frederik, Strandberg, Olof, Smith, Ruben, Weiner, Michael W, 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 C, Perrin, Richard J, Shaw, Leslie M, Khachaturian, Zaven, Carrillo, Maria, Potter, William, Barnes, Lisa, Bernard, Marie, González, Hector, Ho, Carole, Hsiao, John K, Jackson, Jonathan, Masliah, Eliezer, Masterman, Donna, Okonkwo, Ozioma, 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, Kormo, Adrienne, Montine, Tom, Conti, Cat B, 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, 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, and Crawfor, Karen

Subjects
Health Sciences, Neurosciences, Alzheimer's Disease Related Dementias (ADRD), Clinical Research, Acquired Cognitive Impairment, Vascular Cognitive Impairment/Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Biomedical Imaging, Behavioral and Social Science, Alzheimer's Disease, Aging, Neurodegenerative, Brain Disorders, Cerebrovascular, Dementia, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Neurological, Mental health, Humans, Alzheimer Disease, Longitudinal Studies, tau Proteins, Cross-Sectional Studies, Cerebral Cortical Thinning, Positron-Emission Tomography, Brain, Cognition, Apolipoproteins E, Alzheimer's disease, tau, resilience, cognition, PET, MRI, Alzheimer’s Disease Neuroimaging Initiative, Alzheimer’s disease, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

Mechanisms of resilience against tau pathology in individuals across the Alzheimer's disease spectrum are insufficiently understood. Longitudinal data are necessary to reveal which factors relate to preserved cognition (i.e. cognitive resilience) and brain structure (i.e. brain resilience) despite abundant tau pathology, and to clarify whether these associations are cross-sectional or longitudinal. We used a longitudinal study design to investigate the role of several demographic, biological and brain structural factors in yielding cognitive and brain resilience to tau pathology as measured with PET. In this multicentre study, we included 366 amyloid-β-positive individuals with mild cognitive impairment or Alzheimer's disease dementia with baseline 18F-flortaucipir-PET and longitudinal cognitive assessments. A subset (n = 200) additionally underwent longitudinal structural MRI. We used linear mixed-effects models with global cognition and cortical thickness as dependent variables to investigate determinants of cognitive resilience and brain resilience, respectively. Models assessed whether age, sex, years of education, APOE-ε4 status, intracranial volume (and cortical thickness for cognitive resilience models) modified the association of tau pathology with cognitive decline or cortical thinning. We found that the association between higher baseline tau-PET levels (quantified in a temporal meta-region of interest) and rate of cognitive decline (measured with repeated Mini-Mental State Examination) was adversely modified by older age (Stβinteraction = -0.062, P = 0.032), higher education level (Stβinteraction = -0.072, P = 0.011) and higher intracranial volume (Stβinteraction = -0.07, P = 0.016). Younger age, higher education and greater cortical thickness were associated with better cognitive performance at baseline. Greater cortical thickness was furthermore associated with slower cognitive decline independent of tau burden. Higher education also modified the negative impact of tau-PET on cortical thinning, while older age was associated with higher baseline cortical thickness and slower rate of cortical thinning independent of tau. Our analyses revealed no (cross-sectional or longitudinal) associations for sex and APOE-ε4 status on cognition and cortical thickness. In this longitudinal study of clinically impaired individuals with underlying Alzheimer's disease neuropathological changes, we identified education as the most robust determinant of both cognitive and brain resilience against tau pathology. The observed interaction with tau burden on cognitive decline suggests that education may be protective against cognitive decline and brain atrophy at lower levels of tau pathology, with a potential depletion of resilience resources with advancing pathology. Finally, we did not find major contributions of sex to brain nor cognitive resilience, suggesting that previous links between sex and resilience might be mainly driven by cross-sectional differences.

Published
2023

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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5. 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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6. Staging tau pathology with tau PET in Alzheimer’s disease: a longitudinal study

Author

Chen, Shi Dong, Lu, Jia Ying, Li, Hong Qi, Yang, Yu Xiang, Jiang, Jie Hui, Cui, Mei, Zuo, Chuan Tao, Tan, Lan, Dong, Qiang, Yu, Jin Tai, Weiner, Michael W., 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 C., Perrin, Richard J., Shaw, Leslie M., Carrillo, Maria, Potter, William, Barnes, Lisa, Bernard, Marie, González, Hector, Ho, Carole, Hsiao, John K., Jackson, Jonathan, and Masliah, Eliezer

Subjects
Oncology, Male, medicine.medical_specialty, Longitudinal study, tau Proteins, Neurosciences. Biological psychiatry. Neuropsychiatry, Disease, Article, Cellular and Molecular Neuroscience, Alzheimer Disease, Internal medicine, medicine, Humans, Cognitive Dysfunction, Longitudinal Studies, Stage (cooking), Cognitive decline, Biological Psychiatry, Aged, Aged, 80 and over, Amyloid beta-Peptides, medicine.diagnostic_test, business.industry, Cognition, medicine.disease, Psychiatry and Mental health, Positron emission tomography, Positron-Emission Tomography, Biomarker (medicine), Female, Alzheimer's disease, business, Biomarkers, Neuroscience, RC321-571
Abstract

A biological research framework to define Alzheimer’ disease with dichotomized biomarker measurement was proposed by National Institute on Aging–Alzheimer’s Association (NIA–AA). However, it cannot characterize the hierarchy spreading pattern of tau pathology. To reflect in vivo tau progression using biomarker, we constructed a refined topographic 18F-AV-1451 tau PET staging scheme with longitudinal clinical validation. Seven hundred and thirty-four participants with baseline 18F-AV-1451 tau PET (baseline age 73.9 ± 7.7 years, 375 female) were stratified into five stages by a topographic PET staging scheme. Cognitive trajectories and clinical progression were compared across stages with or without further dichotomy of amyloid status, using linear mixed-effect models and Cox proportional hazard models. Significant cognitive decline was first observed in stage 1 when tau levels only increased in transentorhinal regions. Rates of cognitive decline and clinical progression accelerated from stage 2 to stage 3 and stage 4. Higher stages were also associated with greater CSF phosphorylated tau and total tau concentrations from stage 1. Abnormal tau accumulation did not appear with normal β-amyloid in neocortical regions but prompt cognitive decline by interacting with β-amyloid in temporal regions. Highly accumulated tau in temporal regions independently led to cognitive deterioration. Topographic PET staging scheme have potentials in early diagnosis, predicting disease progression, and studying disease mechanism. Characteristic tau spreading pattern in Alzheimer’s disease could be illustrated with biomarker measurement under NIA–AA framework. Clinical–neuroimaging–neuropathological studies in other cohorts are needed to validate these findings.

Published
2021

8. Plasma phosphorylated-tau181 as a predictive biomarker for Alzheimer's amyloid, tau and FDG PET status

Author

Shen, Xue Ning, Huang, Yu Yuan, Chen, Shi Dong, Guo, Yu, Tan, Lan, Dong, Qiang, Yu, Jin Tai, Weiner, Michael W., 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 C., Perrin, Richard J., Shaw, Leslie M., Carrillo, Maria, Potter, William, Barnes, Lisa, Bernard, Marie, González, Hector, Ho, Carole, Hsiao, John K., Jackson, Jonathan, Masliah, Eliezer, Masterman, Donna, and Okonkwo, Ozioma

Subjects
Pathology, medicine.medical_specialty, Aging, Screening test, Amyloid, Clinical Sciences, S amyloid, Neurosciences. Biological psychiatry. Neuropsychiatry, tau Proteins, Neurodegenerative, Predictive markers, Alzheimer's Disease, Article, Cellular and Molecular Neuroscience, Alzheimer Disease, Fluorodeoxyglucose F18, Clinical Research, Acquired Cognitive Impairment, Medicine, Humans, Psychology, Pathological, Biological Psychiatry, Predictive biomarker, screening and diagnosis, Amyloid beta-Peptides, business.industry, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Diagnostic markers, Alzheimer’s Disease Neuroimaging Initiative, Brain pathologies, Pathophysiology, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, Psychiatry and Mental health, Detection, Neurological, Public Health and Health Services, Phosphorylation, Biomedical Imaging, Dementia, business, Biomarkers, RC321-571, 4.2 Evaluation of markers and technologies
Abstract

Plasma phosphorylated-tau181 (p-tau181) showed the potential for Alzheimer’s diagnosis and prognosis, but its role in detecting cerebral pathologies is unclear. We aimed to evaluate whether it could serve as a marker for Alzheimer’s pathology in the brain. A total of 1189 participants with plasma p-tau181 and PET data of amyloid, tau or FDG PET were included from ADNI. Cross-sectional relationships of plasma p-tau181 with PET biomarkers were tested. Longitudinally, we further investigated whether different p-tau181 levels at baseline predicted different progression of Alzheimer’s pathological changes in the brain. We found plasma p-tau181 significantly correlated with brain amyloid (Spearman ρ = 0.45, P P = 0.0003), and FDG PET uptakes (−0.37, P 18.85 pg/ml) at baseline had a higher risk of pathological progression in brain amyloid (HR: 2.32, 95%CI 1.32–4.08) and FDG PET (3.21, 95%CI 2.06–5.01) status. Plasma p-tau181 may be a sensitive screening test for detecting brain pathologies, and serve as a predictive biomarker for Alzheimer’s pathophysiology.

Published
2021

12. Cost-benefit analysis of second-generation antipsychotics and placebo in a randomized trial of the treatment of psychosis and aggression in Alzheimer disease

Author

Rosenheck, Robert A., Leslie, Douglas L., Sindelar, Jody L., Miller, Edward A., Tariot, Peter N., Dagerman, Karen S., Davis, Sonia M., Lebowitz, Barry D., Rabins, Peter, Hsiao, John K., Lieberman, Jeffery A., and Schneider, Lon S.

Subjects
Alzheimer's disease -- Drug therapy, Antipsychotic drugs -- Usage, Psychoses -- Drug therapy, Aggressiveness (Psychology) -- Drug therapy, Drug therapy -- Research, Drug therapy -- Patient outcomes, Health, Psychology and mental health
Published
2007

13. Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial

Author

Keefe, Richard S.E., Bilder, Robert M., Davis, Sonia M., Harvey, Philip D., Palmer, Barton W., Gold, James M., Meltzer, Herbert Y., Green, Michael F., Capuano, George, Stroup, T. Scott, McEvoy, Joseph P., Swartz, Marvin S., Rosenheck, Robert A., Perkins, Dian O., Davis, Clarence E., Hsiao, John K., and Lieberman, Jeffrey A.

Subjects
Schizophrenia -- Drug therapy, Drug therapy -- Patient outcomes, Drug therapy -- Research, Antipsychotic drugs -- Dosage and administration, Antipsychotic drugs -- Research, Neurologic manifestations of general diseases -- Evaluation, Cognition -- Evaluation, Health, Psychology and mental health
Published
2007

14. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease

Author

Schneider, Lon S., Tariot, Pierre N., Dagerman, Karen S., Davis, Sonia M., Hsiao, John K., Ismail, Saleem M., Lebowitz, Barry D., Lyketsos, Constantine G., Ryan, Michael J., Stroup, T. Scott, Sultzer, David L., Weintraub, Daniel, and Lieberman, Jeffrey A.

Subjects
Alzheimer's disease -- Drug therapy, Antipsychotic drugs -- Dosage and administration, Psychoses -- Drug therapy
Abstract

The effectiveness of atypical antipsychotic drugs in outpatients with Alzheimer's disease is assessed. Adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis, aggression, or agitation in patients with Alzheimer's disease.

Published
2006

15. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia

Author

Liberman, Jeffrey A., McEvoy, Joseph P., Rosenheck, Robert A., Keefe, Richard S.E., Davis, Clarence E., Stroup, T. Scott, Swartz, Marvin S., Perkins, Diana O., Davis, Sonia M., Lebowitz, Barry D., Severe, Joanne, and Hsiao, John K.

Subjects
Antipsychotic drugs -- Dosage and administration, Antipsychotic drugs -- Research, Schizophrenia -- Drug therapy
Abstract

A double-blind study was undertaken to compare the effects of a first-generation antipsychotic, perphenazine with four other new drugs on patients suffering from acute schizophrenia. Observations reveal that in the final outcome all five drugs were discontinued by most of the patients due to their ineffectiveness, unbearable side effects, and similar other reasons.

Published
2005

32. Quantitative microdialysis

Author

Morrison, Paul F., primary, Bungay, Peter M., additional, Hsiao, John K., additional, Mefford, Ivan N., additional, Dykstra, Kevin H., additional, and Dedrick, Robert L., additional

Published
1991
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40. Inflammatory Markers in Schizophrenia: Comparing Antipsychotic Effects in Phase 1 of the CATIE Schizophrenia Trial

Author

McEvoy, Joseph P., Davis, Sonia M., Nasrallah, Henry A., Goff, Donald C., Lieberman, Jeffrey A., Hsiao, John K., Swartz, Marvin S., Meyer, Jonathan M., Stroup, T. Scott, and Davis, Vicki G.

Abstract

C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin are systemic inflammatory markers (IM) that positively correlate with cardiovascular (CV) risk. Despite the known CV effects of atypical antipsychotics, there is limited prospective data on IM changes during treatment.

Published
2009
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41. Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia

Author

Rosenheck, Robert A., McEvoy, Joseph P., Severe, Joanne, Lebowitz, Barry D., Scott Stroup, T., Lieberman, Jeffrey A., Keefe, Richard S.E., Davis, Clarence E., Hsiao, John K., Davis, Sonia M., Swartz, Marvin S., and Perkins, Diana O.

Abstract

BACKGROUND The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, perphenazine, with several newer drugs in a double-blind study. METHODS A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments. RESULTS Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P

Published
2005
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42. Cognitive Effects of Atypical Antipsychotic Medications in Patients With Alzheimer's Disease: Outcomes From CATIE-AD

Author

Vigen, Cheryl L.P., primary, Mack, Wendy J., additional, Keefe, Richard S.E., additional, Sano, Mary, additional, Sultzer, David L., additional, Stroup, T. Scott, additional, Dagerman, Karen S., additional, Hsiao, John K., additional, Lebowitz, Barry D., additional, Lyketsos, Constantine G., additional, Tariot, Pierre N., additional, Zheng, Ling, additional, and Schneider, Lon S., additional

Published
2011
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43. Inflammatory Markers in Schizophrenia: Comparing Antipsychotic Effects in Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness Study

Author

Meyer, Jonathan M., primary, McEvoy, Joseph P., additional, Davis, Vicki G., additional, Goff, Donald C., additional, Nasrallah, Henry A., additional, Davis, Sonia M., additional, Hsiao, John K., additional, Swartz, Marvin S., additional, Stroup, T. Scott, additional, and Lieberman, Jeffrey A., additional

Published
2009
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44. O4-04-01: Citalopram compared to atypical antipsychotics for Alzheimer patients who did not previously benefit from treatment: The catie-AD study

Author

Schneider, Lon S., primary, Vigen, Cheryl L.P., additional, Mack, Wendy J., additional, Sultzer, David L., additional, Davis, Sonia M., additional, Weintraub, Daniel, additional, Lyketsos, Constantine G., additional, Zheng, Ling, additional, Dagerman, Karen S., additional, Stroup, T. Scott, additional, Hsiao, John K., additional, Lebowitz, Barry D., additional, and Tariot, Pierre N., additional

Published
2009
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46. Dr. Rosenheck and Colleagues Reply

Author

ROSENHECK, ROBERT, primary, STROUP, T. SCOTT, additional, SWARTZ, M., additional, McEVOY, JOSEPH, additional, DAVIS, SONIA M., additional, KEEFE, RICHARD S.E., additional, HSIAO, JOHN K., additional, and LIEBERMAN, J., additional

Published
2007
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