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22. Building transparency and trust in industry-sponsored clinical research through open access publishing

Author

Barbara DeCastro, Anna Geraci, Jayme Trott, G. Peter Snyder, and Yaswant Dayaram

Subjects
Industry-sponsored research, MPIP, Open Access, Tr, Academies and learned societies, AS1-945, Bibliography. Library science. Information resources
Abstract

A desire for both transparency in research and widespread access to the results of research has led to activism in support of open access publishing. Open access publishing, particularly publishing industry-sponsored research, can be complex. The overarching benefits of, and challenges to, open access are described, illustrated with the initiatives related to Medical Publishing Insights and Practices to help promote a better understanding of open access and its importance in ensuring transparency in industry-sponsored research.

Published
2020
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27. Clearance of interstitial fluid (ISF) and CSF (CLIC) group—part of Vascular Professional Interest Area (PIA)

Author

Roxana O. Carare, Roxana Aldea, Nivedita Agarwal, Brian J. Bacskai, Ingo Bechman, Delphine Boche, Guojun Bu, Diederik Bulters, Alt Clemens, Scott E. Counts, Mony deLeon, Per K. Eide, Silvia Fossati, Steven M. Greenberg, Edith Hamel, Cheryl A. Hawkes, Maya Koronyo‐Hamaoui, Atticus H. Hainsworth, David Holtzman, Masafumi Ihara, Angela Jefferson, Raj N. Kalaria, Christopher M. Kipps, Katja M. Kanninen, Ville Leinonen, JoAnne McLaurin, Scott Miners, Tarja Malm, James A. R. Nicoll, Fabrizio Piazza, Gesine Paul, Steven M. Rich, Satoshi Saito, Andy Shih, Henrieta Scholtzova, Heather Snyder, Peter Snyder, Finnbogi Rutur Thormodsson, Susanne J. vanVeluw, Roy O. Weller, David J. Werring, Donna Wilcock, Mark R. Wilson, Berislav V. Zlokovic, and Ajay Verma

Subjects
cerebrospinal fluid, clearance, interstitial fluid, IPAD, ISTAART, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract

Abstract Two of the key functions of arteries in the brain are (1) the well‐recognized supply of blood via the vascular lumen and (2) the emerging role for the arterial walls as routes for the elimination of interstitial fluid (ISF) and soluble metabolites, such as amyloid beta (Aβ), from the brain and retina. As the brain and retina possess no conventional lymphatic vessels, fluid drainage toward peripheral lymph nodes is mediated via transport along basement membranes in the walls of capillaries and arteries that form the intramural peri‐arterial drainage (IPAD) system. IPAD tends to fail as arteries age but the mechanisms underlying the failure are unclear. In some people this is reflected in the accumulation of Aβ plaques in the brain in Alzheimer's disease (AD) and deposition of Aβ within artery walls as cerebral amyloid angiopathy (CAA). Knowledge of the dynamics of IPAD and why it fails with age is essential for establishing diagnostic tests for the early stages of the disease and for devising therapies that promote the clearance of Aβ in the prevention and treatment of AD and CAA. This editorial is intended to introduce the rationale that has led to the establishment of the Clearance of Interstitial Fluid (ISF) and CSF (CLIC) group, within the Vascular Professional Interest Area of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment.

Published
2020
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28. Prediction and Classification of Alzheimer’s Disease Based on Combined Features From Apolipoprotein-E Genotype, Cerebrospinal Fluid, MR, and FDG-PET Imaging Biomarkers

Author

Yubraj Gupta, Ramesh Kumar Lama, Goo-Rak Kwon, Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, Steven Chao, Scott Mackin, Rema Raman, Erin Drake, Mike Donohue, Gustavo Jimenez, Kelly Harless, Jennifer Salazar, Yuliana Cabrera, Lindsey Hergesheimer, Elizabeth Shaffer, Craig Nelson, David Bickford, Meryl Butters, Michelle Zmuda, Denise Reyes, Kelley M. Faber, Kelly N. Nudelman, Yiu Ho Au, Kelly Scherer, Daniel Catalinotto, Samuel Stark, Elise Ong, and Dariella Fernandez

Subjects
Alzheimer's disease, MCIs (MCI stable), MCIc (MCI converted), sMRI, FDG-PET, CSF, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Alzheimer's disease (AD), including its mild cognitive impairment (MCI) phase that may or may not progress into the AD, is the most ordinary form of dementia. It is extremely important to correctly identify patients during the MCI stage because this is the phase where AD may or may not develop. Thus, it is crucial to predict outcomes during this phase. Thus far, many researchers have worked on only using a single modality of a biomarker for the diagnosis of AD or MCI. Although recent studies show that a combination of one or more different biomarkers may provide complementary information for the diagnosis, it also increases the classification accuracy distinguishing between different groups. In this paper, we propose a novel machine learning-based framework to discriminate subjects with AD or MCI utilizing a combination of four different biomarkers: fluorodeoxyglucose positron emission tomography (FDG-PET), structural magnetic resonance imaging (sMRI), cerebrospinal fluid (CSF) protein levels, and Apolipoprotein-E (APOE) genotype. The Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline dataset was used in this study. In total, there were 158 subjects for whom all four modalities of biomarker were available. Of the 158 subjects, 38 subjects were in the AD group, 82 subjects were in MCI groups (including 46 in MCIc [MCI converted; conversion to AD within 24 months of time period], and 36 in MCIs [MCI stable; no conversion to AD within 24 months of time period]), and the remaining 38 subjects were in the healthy control (HC) group. For each image, we extracted 246 regions of interest (as features) using the Brainnetome template image and NiftyReg toolbox, and later we combined these features with three CSF and two APOE genotype features obtained from the ADNI website for each subject using early fusion technique. Here, a different kernel-based multiclass support vector machine (SVM) classifier with a grid-search method was applied. Before passing the obtained features to the classifier, we have used truncated singular value decomposition (Truncated SVD) dimensionality reduction technique to reduce high dimensional features into a lower-dimensional feature. As a result, our combined method achieved an area under the receiver operating characteristic (AU-ROC) curve of 98.33, 93.59, 96.83, 94.64, 96.43, and 95.24% for AD vs. HC, MCIs vs. MCIc, AD vs. MCIs, AD vs. MCIc, HC vs. MCIc, and HC vs. MCIs subjects which are high relative to single modality results and other state-of-the-art approaches. Moreover, combined multimodal methods have improved the classification performance over the unimodal classification.

Published
2019
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35. Testosterone treatment of late-onset hypogonadism – benefits and risks

Author

Peter Snyder

Subjects
Male, Endocrinology, Bone Density, Hypogonadism, Endocrinology, Diabetes and Metabolism, Humans, Testosterone, Risk Assessment, Aged
Abstract

As men age, their serum testosterone concentration falls, the total testosterone concentration barely but the free testosterone concentration more so. Testosterone treatment of older men who have low testosterone concentrations can ameliorate several consequences of this fall, including libido and sexual activity, distance walked, hemoglobin and volumetric bone mineral density and strength, but not vitality and cognitive function. The possibility that testosterone treatment of late-onset hypogonadism increases the risks of benign prostatic hyperplasia, prostate cancer or heart disease has been suggested but will not be determined until larger and longer trials are conducted.

Published
2022

36. The Influence of Cerebrospinal Fluid Abnormalities and APOE 4 on PHF-Tau Protein: Evidence From Voxel Analysis and Graph Theory

Author

Yuan Li, Zhijun Yao, Yue Yu, Yu Fu, Ying Zou, Bin Hu, for the Alzheimer’s Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Tom Montine, Gustavo Jimenez, Michael Donohue, Devon Gessert, Kelly Harless, Jennifer Salazar, Yuliana Cabrera, Sarah Walter, Lindsey Hergesheimer, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Joseph Quinn, Lisa C. Silbert, Betty Lind, Jeffrey A. Kaye, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Jaimie Ziolkowski, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Javier Villanueva-Meyer, Valory Pavlik, Nathaniel Pacini, Ashley Lamb, Joseph S. Kass, Rachelle S. Doody, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Randy Yeh, Beau Ances, David Winkfield, Maria Carroll, Angela Oliver, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Hillel Grossman, Effie Mitsis, Raj C. Shah, Melissa Lamar, Patricia Samuels, Ranjan Duara, Maria T. Greig-Custo, Rosemarie Rodriguez, Chiadi Onyike, Daniel D’Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Jamika Singleton-Garvin, Anaztasia Ulysse, Mrunalini Gaikwad, P. Murali Doraiswamy, Jeffrey R. Petrella, Olga James, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Jason H. Karlawish, David A. Wolk, Sanjeev Vaishnavi, Christopher M. Clark, Steven E. Arnold, Charles D. Smith, Greg Jicha, Peter Hardy, Riham El Khouli, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Kim Martin, Nancy Kowalksi, Melanie Keltz, Bonnie S. Goldstein, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Gaby Thai, Aimee Pierce, Beatriz Yanez, Elizabeth Sosa, Megan Witbracht, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Ellen Woo, Daniel H.S. Silverman, Edmond Teng, Sarah Kremen, Liana Apostolova, Kathleen Tingus, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Chris (Chinthaka) Heyn, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, William Pavlosky, Irina Rachinsky, Dick Drost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad A. Marshall, Jerome Yesavage, Joy L. Taylor, Steven Chao, Barton Lane, Allyson Rosen, Jared Tinklenberg, Edward Zamrini, Christine M. Belden, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Ntekim E. Oyonumo, Joanne Allard, Olu Ogunlana, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Joel Hetelle, Kathryn DeMarco, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Rawan Tarawneh, Earl A. Zimmerman, Dzintra Celmins, David Hart, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Mia Yang, Akiva Mintz, Rhode Island, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Courtney Bodge, Stephen Salloway, Paul Malloy, Stephen Correia, Athena Lee, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, John Rogers, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Delwyn D. Miller, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Susan K. Schultz, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Christi Leach, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Lindsey Hergesheimen, Jacqueline Hayes, Shannon Finley, Susan Landau, Erin Householder, Karl Friedl, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Bonnie Goldstein, Kimberly S. Martin, Steven G. Potkin, Adrian Preda, Dana Nguyen, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Gad Marshall, Marwan N. Sabbagh, Sandra A. Jacobson, Saba Wolday, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, Scott Mackin, Rema Raman, Erin Drake, Mike Donohue, Elizabeth Shaffer, Craig Nelson, David Bickford, Meryl Butters, Michelle Zmuda, Denise Reyes, Kelley M. Faber, Kelly N. Nudelman, Yiu Ho Au, Kelly Scherer, Daniel Catalinotto, Samuel Stark, Elise Ong, and Dariella Fernandez

Subjects
PHF-Tau, graph theory, network properties, APOE 4, CSF-Tau, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Mild cognitive impairment (MCI) is a transitional state between the cognitive changes in normal aging and Alzheimer’s disease (AD), which induces abnormalities in specific brain regions. Previous studies showed that paired helical filaments Tau (PHF-Tau) protein is a potential pathogenic protein which may cause abnormal brain function and structure in MCI and AD patients. However, the understanding of the PHF-Tau protein network in MCI patients is limited. In this study, 225 subjects with PHF-Tau Positron Emission Tomography (PET) images were divided into four groups based on whether they carried Apolipoprotein E ε4 (APOE 4) or abnormal cerebrospinal fluid Total-Tau (CSF T-Tau). They are two important pathogenic factors that might cause cognitive function impairment. The four groups were: individuals harboring CSF T-Tau pathology but no APOE 4 (APOE 4−T+); APOE 4 carriers with normal CSF T-Tau (APOE 4+T−); APOE 4 carriers with abnormal CSF T-Tau (APOE 4+T+); and APOE 4 noncarriers with abnormal CSF T-Tau (APOE 4−T−). We explored the topological organization of PHF-Tau networks in these four groups and calculated five kinds of network properties: clustering coefficient, shortest path length, Q value of modularity, nodal centrality and degree. Our findings showed that compared with APOE 4−T− group, the other three groups showed different alterations in the clustering coefficient, shortest path length, Q value of modularity, nodal centrality and degree. Simultaneously, voxel-level analysis was conducted and the results showed that compared with APOE 4−T− group, the other three groups were found increased PHF-Tau distribution in some brain regions. For APOE 4+T+ group, positive correlation was found between the value of PHF-Tau distribution in altered regions and Functional Assessment Questionnaire (FAQ) score. Our results indicated that the effects of APOE 4 and abnormal CSF T-Tau may induce abnormalities of PHF-Tau protein and APOE 4 has a greater impact on PHF-Tau than abnormal CSF T-Tau. Our results may be particularly helpful in uncovering the pathophysiology underlying the cognitive dysfunction in MCI patients.

Published
2019
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37. New Perspective for Non-invasive Brain Stimulation Site Selection in Mild Cognitive Impairment: Based on Meta- and Functional Connectivity Analyses

Author

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

Subjects
mild cognitive impairment, non-invasive brain stimulation, stimulation site, meta-analysis, resting state functional connectivity, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

BackgroundNon-invasive brain stimulation (NIBS) has been widely used to treat mild cognitive impairment (MCI). However, there exists no consensus on the best stimulation sites.ObjectiveTo explore potential stimulation locations for NIBS treatment in patients with MCI, combining meta- and resting state functional connectivity (rsFC) analyses.MethodsThe meta-analysis was conducted to identify brain regions associated with MCI. Regions of interest (ROIs) were extracted based on this meta-analysis. The rsFC analysis was applied to 45 MCI patients to determine brain surface regions that are functionally connected with the above ROIs.ResultsWe found that the dorsolateral prefrontal cortex (DLPFC) and inferior frontal gyrus (IFG) were the overlapping brain regions between our results and those of previous studies. In addition, we recommend that the temporoparietal junction (including the angular gyrus), which was found in both the meta- and rsFC analysis, should be considered in NIBS treatment of MCI. Furthermore, the bilateral orbital prefrontal gyrus, inferior temporal gyrus, medial superior frontal gyrus, and right inferior occipital gyrus may be potential brain stimulation sites for NIBS treatment of MCI.ConclusionOur results provide several potential sites for NIBS, such as the DLFPC and IFG, and may shed light on the locations of NIBS sites in the treatment of patients with MCI.

Published
2019
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38. Performing Sparse Regularization and Dimension Reduction Simultaneously in Multimodal Data Fusion

Author

Zhengshi Yang, Xiaowei Zhuang, Christopher Bird, Karthik Sreenivasan, Virendra Mishra, Sarah Banks, Dietmar Cordes, the Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, Steven Chao, Scott Mackin, Rema Raman, Erin Drake, Mike Donohue, Gustavo Jimenez, Kelly Harless, Jennifer Salazar, Yuliana Cabrera, Lindsey Hergesheimer, Elizabeth Shaffer, Craig Nelson, David Bickford, Meryl Butters, Michelle Zmuda, Denise Reyes, Kelley M. Faber, Kelly N. Nudelman, Yiu Ho Au, Kelly Scherer, Daniel Catalinotto, Samuel Stark, Elise Ong, and Dariella Fernandez

Subjects
sparse principal component analysis, PCA, canonical correlation analysis, CCA, data fusion, mild cognitive impairment, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Collecting multiple modalities of neuroimaging data on the same subject is increasingly becoming the norm in clinical practice and research. Fusing multiple modalities to find related patterns is a challenge in neuroimaging analysis. Canonical correlation analysis (CCA) is commonly used as a symmetric data fusion technique to find related patterns among multiple modalities. In CCA-based data fusion, principal component analysis (PCA) is frequently applied as a preprocessing step to reduce data dimension followed by CCA on dimension-reduced data. PCA, however, does not differentiate between informative voxels from non-informative voxels in the dimension reduction step. Sparse PCA (sPCA) extends traditional PCA by adding sparse regularization that assigns zero weights to non-informative voxels. In this study, sPCA is incorporated into CCA-based fusion analysis and applied on neuroimaging data. A cross-validation method is developed and validated to optimize the parameters in sPCA. Different simulations are carried out to evaluate the improvement by introducing sparsity constraint to PCA. Four fusion methods including sPCA+CCA, PCA+CCA, parallel ICA and sparse CCA were applied on structural and functional magnetic resonance imaging data of mild cognitive impairment subjects and normal controls. Our results indicate that sPCA significantly can reduce the impact of non-informative voxels and lead to improved statistical power in uncovering disease-related patterns by a fusion analysis.

Published
2019
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39. Quantitative 18F-AV1451 Brain Tau PET Imaging in Cognitively Normal Older Adults, Mild Cognitive Impairment, and Alzheimer's Disease Patients

Author

Qian Zhao, Min Liu, Lingxia Ha, Yun Zhou, Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, Steven Chao, Scott Mackin, Rema Raman, Erin Drake, Mike Donohue, Gustavo Jimenez, Kelly Harless, Jennifer Salazar, Yuliana Cabrera, Lindsey Hergesheimer, Elizabeth Shaffer, Craig Nelson, David Bickford, Meryl Butters, Michelle Zmuda, Denise Reyes, Kelley M. Faber, Kelly N. Nudelman, Yiu Ho Au, Kelly Scherer, Daniel Catalinotto, Samuel Stark, Elise Ong, and Dariella Fernandez

Subjects
18F-AV1451, Tau PET, cognitively normal, mild cognition impairment, Alzheimer's disease, Neurology. Diseases of the nervous system, RC346-429
Abstract

Recent developments of tau Positron Emission Tomography (PET) allows assessment of regional neurofibrillary tangles (NFTs) deposition in human brain. Among the tau PET molecular probes, 18F-AV1451 is characterized by high selectivity for pathologic tau aggregates over amyloid plaques, limited non-specific binding in white and gray matter, and confined off-target binding. The objectives of the study are (1) to quantitatively characterize regional brain tau deposition measured by 18F-AV1451 PET in cognitively normal older adults (CN), mild cognitive impairment (MCI), and AD participants; (2) to evaluate the correlations between cerebrospinal fluid (CSF) biomarkers or Mini-Mental State Examination (MMSE) and 18F-AV1451 PET standardized uptake value ratio (SUVR); and (3) to evaluate the partial volume effects on 18F-AV1451 brain uptake.Methods: The study included total 115 participants (CN = 49, MCI = 58, and AD = 8) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed 18F-AV1451 PET images, structural MRIs, and demographic and clinical assessments were downloaded from the ADNI database. A reblurred Van Cittertiteration method was used for voxelwise partial volume correction (PVC) on PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. The parametric images of 18F-AV1451 SUVR relative to cerebellum were calculated. The ROI SUVR measurements from PVC and non-PVC SUVR images were compared. The correlation between ROI 18F-AV1451 SUVR and the measurements of MMSE, CSF total tau (t-tau), and phosphorylated tau (p-tau) were also assessed.Results:18F-AV1451 prominently specific binding was found in the amygdala, entorhinal cortex, parahippocampus, fusiform, posterior cingulate, temporal, parietal, and frontal brain regions. Most regional SUVRs showed significantly higher uptake of 18F-AV1451 in AD than MCI and CN participants. SUVRs of small regions like amygdala, entorhinal cortex and parahippocampus were statistically improved by PVC in all groups (p < 0.01). Although there was an increasing tendency of 18F-AV-1451 SUVRs in MCI group compared with CN group, no significant difference of 18F-AV1451 deposition was found between CN and MCI brains with or without PVC (p > 0.05). Declined MMSE score was observed with increasing 18F-AV1451 binding in amygdala, entorhinal cortex, parahippocampus, and fusiform. CSF p-tau was positively correlated with 18F-AV1451 deposition. PVC improved the results of 18F-AV-1451 tau deposition and correlation studies in small brain regions.Conclusion: The typical deposition of 18F-AV1451 tau PET imaging in AD brain was found in amygdala, entorhinal cortex, fusiform and parahippocampus, and these regions were strongly associated with cognitive impairment and CSF biomarkers. Although more deposition was observed in MCI group, the 18F-AV-1451 PET imaging could not differentiate the MCI patients from CN population. More tau deposition related to decreased MMSE score and increased level of CSF p-tau, especially in ROIs of amygdala, entorhinal cortex and parahippocampus. PVC did improve the results of tau deposition and correlation studies in small brain regions and suggest to be routinely used in 18F-AV1451 tau PET quantification.

Published
2019
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46. Corrigendum: Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images

Author

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

Subjects
mild cognitive impairment, conversion, cortical feature, sparse-constrained regression, feature reduction, classification, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Published
2017
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48. Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images

Author

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

Subjects
mild cognitive impairment, conversion, cortical feature, sparse-constrained regression, feature reduction, classification, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI). Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions, and further differentiate MCI patients from normal states. Four cortical features, namely, gray matter volume, cortical thickness, surface area, and mean curvature, were explored for discriminative analysis among three groups including the stable MCI (sMCI), the converted MCI (cMCI), and the normal control (NC) groups. In this study, 158 subjects (72 NC, 46 sMCI, and 40 cMCI) were selected from the Alzheimer's Disease Neuroimaging Initiative. A sparse-constrained regression model based on the l2-1-norm was introduced to reduce the feature dimensionality and retrieve essential features for the discrimination of the three groups by using a support vector machine (SVM). An optimized strategy of feature addition based on the weight of each feature was adopted for the SVM classifier in order to achieve the best classification performance. The baseline cortical features combined with the longitudinal measurements for 2 years of follow-up data yielded prominent classification results. In particular, the cortical thickness produced a classification with 98.84% accuracy, 97.5% sensitivity, and 100% specificity for the sMCI–cMCI comparison; 92.37% accuracy, 84.78% sensitivity, and 97.22% specificity for the cMCI–NC comparison; and 93.75% accuracy, 92.5% sensitivity, and 94.44% specificity for the sMCI–NC comparison. The best performances obtained by the SVM classifier using the essential features were 5–40% more than those using all of the retained features. The feasibility of the cortical features for the recognition of anatomical patterns was certified; thus, the proposed method has the potential to improve the clinical diagnosis of sub-types of MCI and predict the risk of its conversion to Alzheimer's disease.

Published
2017
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49. OR25-5 Adverse Cardiovascular Events and Cause Mortality in Men During Testosterone Treatment: Individual Patient and Aggregate Data Meta-Analyses

Author

Marianne Andersen, Kristina Antonic, Lorna Aucott, Shalender Bhasin, Siladitya Bhattacharya, Miriam Brazzelli, Moira Cruickshank, Waljit Dhillo, Susan Ellenberg, Marielle Emmelot-Vonk, Emily Gianatti, Erik Giltay, Mathis Grossmann, Geoff Hackett, Kerry Hildreth, Jemma Hudson, Leonard Marks, Richard Quinton, Peter Snyder, Johan Svartberg, Hui Tan, Lisa Tenover, Thomas Travison, Frederick Wu, and Channa Jayasena

Subjects
Endocrinology, Diabetes and Metabolism
Abstract

Background The cardiovascular safety of testosterone treatment in low testosterone is widely acknowledged to be unclear. Testosterone increases haematocrit, thereby potentially increasing venous thromboembolism risk. The FDA lists cardiovascular risk and stroke as adverse effects of testosterone. Systematic reviews and meta-analyses of published data have limited ability to confirm source data quality and categorisation. Some published meta-analyses have included participants with distinct risk profiles (e.g. cancer, HIV), with serum testosterone atypical for hypogonadism (>12nmol/L), short durations of testosterone treatment, and studies without placebo treatment. Furthermore, subtypes of cardiovascular or cerebrovascular events (e.g. stable angina) during testosterone treatment are seldom published, so have not been analysed previously. Objective Evaluate frequencies of all-cause mortality, and all cardiovascular or cerebrovascular event subtypes, and analyse efficacy of testosterone monotherapy compared to placebo for men with low testosterone, using individual patient data (IPD) and aggregate data meta-analyses. Methods MEDLINE, EMBASE, Science Citation Index, CENTRAL and clinical trial registries (PROSPERO CRD42018111005) were searched for placebo-controlled RCTs including men with serum testosterone Results IPD were obtained from 17 of 35 eligible RCTs (3431/5601 participants) in men with low testosterone. Most participants had functional hypogonadism. Risks of cardiovascular and/or cerebrovascular events were similar between the testosterone and placebo arms (testosterone 120/1601, 7.5%; placebo, 110/1519, 7.2% OR 1.07, 95% CI 0.81-1.42 p=0.62). Frequencies of all cardiovascular or cerebrovascular event subtypes were also similar between testosterone and placebo arms, but testosterone increased risks of oedema and erythrocytosis. No subgroups at higher cardiovascular and/or cerebrovascular event risk were identified. Fewer deaths were recorded in the testosterone arm, but this difference was non-significant (testosterone, 6/1621, 0.4%; placebo, 12/1537, 0.8% OR 0.46, 95% CI 0.17-1.24 p=0.13). Testosterone significantly reduced serum total cholesterol, high-density lipoprotein (HDL), and triglycerides versus placebo. No significant differences in serum low-density lipoprotein (LDL), blood pressure, glycaemic parameters, diabetes incidence or prostate outcomes were observed between groups. Testosterone had positive, albeit varied, effects on quality of life and sexual function. Conclusions This is the most comprehensive study to date interrogating the safety of testosterone treatment in men with low testosterone. We were unable to find evidence from our IPD meta-analyses that testosterone increases risks of mortality or cardiovascular and/or cerebrovascular events in the short- to medium-term in men with low testosterone, most of whom have various forms of functional hypogonadism. These data provide some reassurance to men with low testosterone and their clinicians about the safety of testosterone in the short-to-medium term although more long-term data are required.Acknowledgement: NIHR TestES Consortium. Presentation: Monday, June 13, 2022 12:00 p.m. - 12:15 p.m.

Published
2022

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