Search

Your search keyword '"Hillel Grossman"' showing total 89 results
Start Over Author "Hillel Grossman"
89 results on '"Hillel Grossman"'

1. Sex Modulates the Pathological Aging Effect on Caudate Functional Connectivity in Mild Cognitive Impairment

Author

Zhengshi Yang, Jessica Z. K. Caldwell, Jeffrey L. Cummings, Aaron Ritter, Jefferson W. Kinney, Dietmar Cordes, The Alzheimer's Disease Neuroimaging Initiative (ADNI), Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Enchi Liu, Tom Montine, Anthony Gamst, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Danielle Harvey, John Kornak, Anders Dale, Matthew Bernstein, Joel Felmlee, Nick Fox, Paul Thompson, Norbert Schuff, Gene Alexander, Charles DeCArli, Dan Bandy, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Nigel J. Cairns, Lisa Taylor-Reinwald, J. Q. Trojanowki, Les Shaw, Virginia M.Y. Lee, Magdalena Korecka, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Zaven Khachaturian, Richard Frank, Peter J. Snyder, Susan Molchan, Jeffrey Kaye, Joseph Quinn, Betty Lind, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Bryan M. Spann, James Brewer, Helen Vanderswag, Judith L. Heidebrink, Joanne L. Lord, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Munir Chowdhury, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, John C. Morris, Beau Ances, Maria Carroll, Sue Leon, Mark A. Mintun, Stacy Schneider, Daniel Marson, Randall Griffith, David Clark, Hillel Grossman, Effie Mitsis, Aliza Romirowsky, Leyla deToledo-Morrell, Raj C. Shah, Ranjan Duara, Daniel Varon, Peggy Roberts, Marilyn Albert, Chiadi Onyike, Stephanie Kielb, Henry Rusinek, Mony J de Leon, Lidia Glodzik, P. Murali Doraiswamy, Jeffrey R. Petrella, Edward R. Coleman, Steven E. Arnold, Jason H. Karlawish, David Wolk, Charles D. Smith, Greg Jicha, Peter Hardy, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Ruth A. Mulnard, Gaby Thai, Catherine Mc-Adams-Ortiz, Ramon Diaz-Arrastia, Kristen Martin-Cook, Michael DeVous, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Heather S Anderson, Russell H. Swerdlow, Liana Apostolova, Po H. Lu, George Bartzokis, Daniel H.S. Silverman, Neill R Graff-Radford, Francine Parfitt, Heather Johnson, Martin Farlow, Scott Herring, Ann M. Hake, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Howard Feldman, Michele Assaly, Andrew KertesZ, John Rogers, Dick Trost, Charles Bernick, Donna Munic, Diana Kerwin, Marek-Marsel Mesulam, Kristine Lipowski, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Walter Martinez, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Meghan Frey, Allyson Rosen, Jared Tinklenberg, Marwan Sabbagh, Christine Belden, Sandra Jacobson, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Salome K. Bwayo, Alan Lerner, Leon Hudson, Paula Ogrocki, Evan Fletcher, Owen Carmichael, John Olichney, Charles DeCarli, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Steven G. Potkin, Adrian Preda, Dana Nguyen, Pierre Tariot, Adam Fleisher, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Barry A. Hendin, Douglas W. Scharre, Maria Kataki, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Robert B. Santulli, Eben S. Schwartz, Kaycee M. Sink, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Henry Querfurth, Geoffrey Tremont, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, Jacobo Mintzer, Crystal Flynn Longmire, and Kenneth Spicer

Subjects
aging effect, caudate, mild cognitive impairment, functional connectivity, Alzheimer's Disease, sex difference, Psychiatry, RC435-571
Abstract

PurposeTo assess the pathological aging effect on caudate functional connectivity among mild cognitive impairment (MCI) participants and examine whether and how sex and amyloid contribute to this process.Materials and MethodsTwo hundred and seventy-seven functional magnetic resonance imaging (fMRI) sessions from 163 cognitive normal (CN) older adults and 309 sessions from 139 participants with MCI were included as the main sample in our analysis. Pearson's correlation was used to characterize the functional connectivity (FC) between caudate nuclei and each brain region, then caudate nodal strength was computed to quantify the overall caudate FC strength. Association analysis between caudate nodal strength and age was carried out in MCI and CN separately using linear mixed effect (LME) model with covariates (education, handedness, sex, Apolipoprotein E4, and intra-subject effect). Analysis of covariance was conducted to investigate sex, amyloid status, and their interaction effects on aging with the fMRI data subset having amyloid status available. LME model was applied to women and men separately within MCI group to evaluate aging effects on caudate nodal strength and each region's connectivity with caudate nuclei. We then evaluated the roles of sex and amyloid status in the associations of neuropsychological scores with age or caudate nodal strength. An independent cohort was used to validate the sex-dependent aging effects in MCI.ResultsThe MCI group had significantly stronger age-related increase of caudate nodal strength compared to the CN group. Analyzing women and men separately revealed that the aging effect on caudate nodal strength among MCI participants was significant only for women (left: P = 6.23 × 10−7, right: P = 3.37 × 10−8), but not for men (P > 0.3 for bilateral caudate nuclei). The aging effects on caudate nodal strength were not significantly mediated by brain amyloid burden. Caudate connectivity with ventral prefrontal cortex substantially contributed to the aging effect on caudate nodal strength in women with MCI. Higher caudate nodal strength is significantly related to worse cognitive performance in women but not in men with MCI.ConclusionSex modulates the pathological aging effects on caudate nodal strength in MCI regardless of amyloid status. Caudate nodal strength may be a sensitive biomarker of pathological aging in women with MCI.

Published
2022
Full Text
View/download PDF

2. 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
Full Text
View/download PDF

3. 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
Full Text
View/download PDF

4. 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
Full Text
View/download PDF

5. 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
Full Text
View/download PDF

6. 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
Full Text
View/download PDF

7. 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
Full Text
View/download PDF

8. 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
Full Text
View/download PDF

11. Cross‐ancestry effect of APOE on cognitive performance

Author

Nadia V. Harerimana, Clara Li, Carolyn W Zhu, Mary Sano, Hillel Grossman, Alison Goate, and Shea J Andrews

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2022

12. Adapting Alzheimer Disease and Related Dementias Clinical Research Evaluations in the Age of COVID-19

Author

Margaret Sewell, Jane Martin, Mary Sano, Corbett Schimming, Carolyn W. Zhu, Amy S. Aloysi, Judith Neugroschl, Clara Li, Hillel Grossman, Michael T Kinsella, and Maria Loizos

Subjects
Gerontology, MEDLINE, Telehealth, Article, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Pandemic, Humans, Medicine, Dementia, 030212 general & internal medicine, Data collection, SARS-CoV-2, business.industry, Data Collection, COVID-19, medicine.disease, Psychiatry and Mental health, Clinical Psychology, Cohort, Observational study, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Research center
Abstract

In March 2020, the novel coronavirus (COVID-19) became a global pandemic that would cause most in-person visits for clinical studies to be put on pause. Coupled with protective stay at home guidelines, clinical research at the Icahn School of Medicine at Mount Sinai Alzheimer's Disease Research Center (ISMMS ADRC) needed to quickly adapt to remain operational and maintain our cohort of research participants. Data collected by the ISMMS ADRC as well as from other National Institute on Aging (NIA) Alzheimer Disease centers, follows the guidance of the National Alzheimer Coordinating Center (NACC). However, at the start of this pandemic, NACC had no alternative data collection mechanisms that could accommodate these safety guidelines. To stay in touch with our cohort and to ensure continued data collection under different stages of quarantine, the ISMMS ADRC redeployed their work force to continue their observational study via telehealth assessment. On the basis of this experience and that of other centers, NACC was able to create a data collection process to accommodate remote assessment in mid-August. Here we review our experience in filling the gap during this period of isolation and describe the adaptations for clinical research, which informed the national dialog for conducting dementia research in the age of COVID-19 and beyond.

Published
2021

13. Specific depression dimensions are associated with a faster rate of cognitive decline in older adults

Author

Laili, Soleimani, Michal, Schnaider Beeri, Hillel, Grossman, Mary, Sano, and Carolyn W, Zhu

Subjects
Psychiatry and Mental health, Neurology (clinical)
Abstract

Understanding the relationship between different depression presentations and cognitive outcome may elucidate high-risk sub-groups for cognitive decline.In this study we utilized longitudinal data from the National Alzheimer's Coordinating Center (NACC) on 16,743 initially not demented older adults followed every 12 months for an average of 5 years. Depression dimensions were defined based on the 15-item Geriatric Depression Scale (GDS-15), that is, dysphoric mood, Withdrawal-Apathy-Vigor (WAV), anxiety, hopelessness, and subjective memory complaint (SMC).After adjustment for sociodemographic and clinical covariates, SMC and hopelessness were associated with faster decline in global cognition and all cognitive domains and WAV with decline executive function. Dysphoric mood and anxiety were not associated with a faster cognitive decline in any of the cognitive domains.Different depression dimensions had different associations with the rate of cognitive decline, suggesting distinct pathophysiology and the need for more targeted interventions.

Published
2022

15. Socio‐psychological impact of COVID‐19 on a diverse cohort of older adult research participants in New York

Author

Maria Loizos, Margaret Sewell, Judith A Neugroschl, Carolyn W Zhu, Clara Li, Xiaoyi Zeng, Kelly Pun, Nelly Velasco, Carly Tocco, Faye Sheppard, Allison Ardolino, Caroline Meuser, Jonathan Greenberg, Kirsten Evans, Michael T Kinsella, Amy Aloysi, Hillel Grossman, and Mary Sano

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published
2021

16. The 32-Item Multilingual Naming Test: Cultural and Linguistic Biases in Monolingual Chinese-Speaking Older Adults

Author

Maria Loizos, Margaret Sewell, Jane Martin, Mary Sano, Mengfei Xu, Dongming Cai, Jeanne A Teresi, Amy S. Aloysi, Xiaoyi Zeng, Hillel Grossman, Katja Ocepek-Welikson, Andrew Joseph, Carolyn W. Zhu, Judith Neugroschl, Clara Li, and Mildred Ramirez

Subjects
biology, General Neuroscience, Witch, Linguistics, Neuropsychological Tests, medicine.disease, biology.organism_classification, Test (assessment), Psychiatry and Mental health, Clinical Psychology, Word lists by frequency, Bias, Alzheimer Disease, Gauge (instrument), medicine, Dementia, Humans, Neurology (clinical), China, Psychology, Inclusion (education), Chinese americans, Aged, Language
Abstract

Objectives:This study describes the performance of the Multilingual Naming Test (MINT) by Chinese American older adults who are monolingual Chinese speakers. An attempt was also made to identify items that could introduce bias and warrant attention in future investigation.Methods:The MINT was administered to 67 monolingual Chinese older adults as part of the standard dementia evaluation at the Alzheimer’s Disease Research Center (ADRC) at the Icahn School of Medicine at Mount Sinai (ISMMS), New York, USA. A diagnosis of normal cognition (n = 38), mild cognitive impairment (n = 12), and dementia (n = 17) was assigned to all participants at clinical consensus conferences using criterion sheets developed at the ADRC at ISMMS.Results:MINT scores were negatively correlated with age and positively correlated with education, showing sensitivity to demographic factors. One item, butterfly, showed no variations in responses across diagnostic groups. Inclusion of responses from different regions of China changed the answers from “incorrect” to “correct” on 20 items. The last five items, porthole, anvil, mortar, pestle, and axle, yielded a high nonresponse rate, with more than 70% of participants responding with “I don’t know.” Four items, funnel, witch, seesaw, and wig, were not ordered with respect to item difficulty in the Chinese language. Two items, gauge and witch, were identified as culturally biased for the monolingual group.Conclusions:Our study highlights the cultural and linguistic differences that might influence the test performance. Future studies are needed to revise the MINT using more universally recognized items of similar word frequency across different cultural and linguistic groups.

Published
2021

17. Mail and Telephone Outreach from Electronic Health Records for Research Participation on Cognitive Health and Aging

Author

Margaret Sewell, Nelly Velasco, Carolyn W. Zhu, Mary Sano, A. Ardolino, K. Pun, Hillel Grossman, Judith Neugroschl, Clara Li, and Michael T Kinsella

Subjects
Gerontology, Response rate (survey), Aging, Geriatrics gerontology, business.industry, Patient Selection, Health records, Healthy Volunteers, Article, Cognitive health, Telephone, Outreach, Cognition, Medicine, Electronic Health Records, Humans, Cognitive Dysfunction, Postal Service, Clinical care, Recruitment methods, Cognitive impairment, business, Aged
Abstract

Objectives: This report describes the efficacy and utility of recruiting older individuals by mail to participate in research on cognitive health and aging using Electronic Health Records (EHR). Methods: Individuals age 65 or older identified by EHR in the Mount Sinai Health System as likely to have Mild Cognitive Impairment (MCI) were sent a general recruitment letter (N=12,951). A comparison group of individuals with comparable age and matched for gender also received the letter (N=3,001). Results: Of the 15,952 individuals who received the mailing, 953 (6.0%) responded. 215 (1.3%) declined further contact. Overall rate of expression of interest was 4.6%. Of the 738 individuals who responded positively to further contact, 321 indicated preference for further contact by telephone. Follow-up of these individuals yielded 30 enrollments (0.2% of 15,952). No differences in response rate were noted between MCI and comparison groups, but the comparison group yielded higher enrollment. 6 individuals who were not the intended recipients of mailing but nevertheless contacted our study were also enrolled. Conclusions: Mailings to individuals identified through a trusted source, such as a medical center from which they have received clinical care, may be a viable means of reaching individuals within this age group as this effort yielded a low rejection rate. However, EHR information did not enhance study enrollment. Implications for improving recruitment are discussed.

Published
2021

18. Why Do They Just Sit? Apathy as a Core Symptom of Alzheimer Disease

Author

Carolyn W. Zhu, Mary Sano, and Hillel Grossman

Subjects
Male, medicine.medical_specialty, Clinical Dementia Rating, Apathy, Neuropsychological Tests, Alzheimer Disease, Activities of Daily Living, Humans, Medicine, Dementia, Cognitive decline, Psychiatry, Depression (differential diagnoses), Aged, Core (anatomy), Depression, business.industry, medicine.disease, Psychiatry and Mental health, Cross-Sectional Studies, Female, Functional status, Geriatrics and Gerontology, medicine.symptom, Alzheimer's disease, business
Abstract

Objective Apathy is common in Alzheimer disease (AD) and has a far-reaching impact on patients’ clinical course and management needs. However, it is unclear if apathy is an integral component of AD or a manifestation of depression in cognitive decline. This study aims to examine interrelationships between apathy, depression, and function. Methods This was a cross-sectional study of well-characterized AD patients in the National Alzheimer's Coordinating Center Uniform Data Set with a Clinical Dementia Rating (CDR) between 0.5 and 2. Participants’ function was measured using the Functional Assessment Questionnaire. Apathy and depression were measured using clinician judgment and informant-reported Neuropsychiatric Inventory–Questionnaire. Dementia severity was categorized by CDR. Results Sample included 7,679 participants (55.7% men) with a mean (standard deviation) age of 74.9 (9.7) years; 3,197 (41.6%) had apathy based on clinician judgment. Among those with apathy, approximately half had no depression. Presence of apathy was associated with 21%, 10%, and 3% worsening in function compared with those without apathy in CDR 0.5, 1, and 2 groups, respectively. Depression was not independently associated with functional status. Results revealed no interaction between apathy and depression. Conclusion Apathy, but not depression, was significantly associated with worse function, with the strongest effects in mild dementia. Results emphasize the need for separate assessments of apathy and depression in the evaluation and treatment of patients with dementia. Understanding their independent effects on function will help identify patients who may benefit from more targeted management strategies.

Published
2019

19. Amyloid imaging for cognitive studies in cohorts with racial and ethnic diversity

Author

Trey Hedden, Hillel Grossman, Amy S. Aloysi, Maria Loizos, Carolyn W. Zhu, Michael T Kinsella, Judith Neugroschl, and Mary Sano

Subjects
Amyloid, Epidemiology, business.industry, Health Policy, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Neuroimaging, Cultural diversity, Medicine, Neurology (clinical), Geriatrics and Gerontology, business, Neuroscience
Published
2020

20. Natural history of apathy in Alzheimer’s disease

Author

Hillel Grossman, Carolyn W. Zhu, and Mary Sano

Subjects
medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Disease, Natural history, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, Apathy, Neurology (clinical), Geriatrics and Gerontology, medicine.symptom, Psychiatry, business
Published
2020

21. Clinical versus neuropathological diagnosis in an ADRC sample: Factors impacting diagnostic concordance rates

Author

Hillel Grossman, Carolyn W. Zhu, Keith H. Radler, Mikayla Haas, Dushyant P. Purohit, Judith Neugroschl, Mary Sano, and Margaret Sewell

Subjects
Pathology, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Diagnostic concordance, Sample (statistics), Neuropathology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Medicine, Neurology (clinical), Geriatrics and Gerontology, business
Published
2020

22. Design Considerations for Mobile Health Applications Targeting Older Adults

Author

Carolyn W. Zhu, Mary Sano, Judith Neugroschl, Clara Li, Maria Loizos, Xiaoyi Zeng, Corbett Schimming, Jane Martin, Margaret Sewell, Dongming Cai, Amy S. Aloysi, and Hillel Grossman

Subjects
020205 medical informatics, Internet privacy, 02 engineering and technology, Patient care, Article, 03 medical and health sciences, 0302 clinical medicine, Software Design, 0202 electrical engineering, electronic engineering, information engineering, Humans, Mobile technology, 030212 general & internal medicine, mHealth, Aged, Health management system, business.industry, General Neuroscience, Usability, General Medicine, Mobile Applications, Telemedicine, Psychiatry and Mental health, Clinical Psychology, Disease prevention, Geriatrics and Gerontology, business, Delivery of Health Care, User-Centered Design
Abstract

Mobile technologies are becoming ubiquitous in the world, changing the way we communicate and provide patient care and services. Some of the most compelling benefits of mobile technologies are in the areas of disease prevention, health management, and care delivery. For all the advances that are occurring in mobile health, its full potential for older adults is only starting to emerge. Yet, existing mobile health applications have design flaws that may limit usability by older adults. The aim of this paper is to review barriers and identify knowledge gaps where more research is needed to improve the accessibility of mobile health use in aging populations. The same observations might apply to those who are not elderly, including individuals suffering from severe mental or medical illnesses.

Published
2020

23. A randomized, double-blind, placebo-controlled trial of resveratrol with glucose and malate (RGM) to slow the progression of Alzheimer's disease: A pilot study

Author

Hillel Grossman, Xiaodong Luo, Amanda Burden, Carolyn W. Zhu, Judith Neugroschl, Susan Parker, and Mary Sano

Subjects
0301 basic medicine, medicine.medical_specialty, Efficacy, Placebo-controlled study, Disease, Resveratrol, Placebo, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pharmacotherapy, Statistical significance, Internal medicine, Medicine, Double-blind methods, Generalized estimating equation, business.industry, Featured Article, 3. Good health, Psychiatry and Mental health, 030104 developmental biology, Tolerability, chemistry, Neurology (clinical), Drug therapy, Safety, business, 030217 neurology & neurosurgery
Abstract

Introduction Human studies on low-dose resveratrol are scarce. This study aims to evaluate the safety, tolerability, and efficacy of an oral preparation of resveratrol, glucose, and malate (RGM) in slowing the progression of Alzheimer's disease (AD). Methods Thirty-nine subjects with mild to moderate AD who were free of life-threatening disease and who did not have contraindications to the use of the study product were screened. Progression of AD was measured by change in the cognitive portion of the Alzheimer's Disease Assessment Scale–cognitive subscale. Secondary outcomes included Clinician's Global Impression of Change, Mini–Mental State Examination, Alzheimer's Disease Cooperative Study–Activities of Daily Living Scale, and Neuropsychiatric Inventory. 15 mL of the following preparation per dose, i.e., 5 g dextrose, 5 g malate, and 5 mg resveratrol, or matching placebo was ingested with an 8 oz glass of commercial unsweetened grape juice twice a day for 1 year. Group differences in the rate of change in the outcome measures were examined using generalized estimating equations. Results The treatment and control groups were similar on all of the screening variables. At 12 months, change scores on Alzheimer's Disease Assessment Scale–cognitive subscale, Mini–Mental State Examination, Alzheimer's Disease Cooperative Study–Activities of Daily Living Scale, or Neuropsychiatric Inventory all showed less deterioration in the treatment than the control group; however, none of the change scores reached statistical significance. The most common AE were falls, all in the control group. None of the falls were deemed to be study related. Conclusion Low-dose oral resveratrol is safe and well tolerated. Interpretation of the effects on clinical outcomes trajectories remains uncertain. A larger study is required to determine whether low-dose resveratrol may be beneficial. Trial Registration ClinicalTrials.gov ( NCT00678431 ), Registered 05/15/2008.

Published
2018

24. Cognitive test battery for evaluating elderly Chinese Americans

Author

Dongming Cai, Jane Martin, Mari Umpierre, Mary Sano, Xiaoyi Zeng, QiYing Huang, Carolyn W. Zhu, Hillel Grossman, Judith Neugroschl, and Clara Li

Subjects
Male, First language, Pilot Projects, Disease, Neuropsychological Tests, Logistic regression, Article, Executive Function, 03 medical and health sciences, Cognition, 0302 clinical medicine, Alzheimer Disease, Memory, Statistical significance, Humans, Cognitive Dysfunction, Aged, Demography, Language, Chinese americans, Asian, 030214 geriatrics, United States, Cognitive test, Psychiatry and Mental health, Clinical Psychology, Female, Cognitive Assessment System, Geriatrics and Gerontology, Psychology, Gerontology, 030217 neurology & neurosurgery, Clinical psychology
Abstract

Objectives:This study aimed to determine the diagnostic utility of a Chinese test battery for evaluating cognitive loss in elderly Chinese Americans.Methods:Data from a pilot study at the Mount Sinai Alzheimer’s Disease Research Center was examined. All participants were > 65 years old, primarily Chinese speaking, with adequate sensorimotor capacity to complete cognitive tests. A research diagnosis of normal mild cognitive impairment (MCI) or Alzheimer’s disease (AD) was assigned to each participant in consensus conference. Composite scores were created to summarize test performance on overall cognition, memory, attention executive function, and language. Multivariable logistic regression models were used to assess the sensitivity of each cognitive domain for discriminating three diagnostic categories. Adjustment was made for demographic variables (i. e., age, gender, education, primary language, and years living in the USA).Results:The sample included 67 normal, 37 MCI, and 12 AD participants. Performance in overall cognition, memory, and attention executive function was significantly worse in AD than in MCI, and performance in MCI was worse than in normal controls. Language performance followed a similar pattern, but differences did not achieve statistical significance among the three diagnostic groups.Conclusions:This study highlights the need for cognitive assessment in elderly Chinese immigrants.

Published
2018

25. Longitudinal Cognitive Profiles in Diabetes: Results From the National Alzheimer's Coordinating Center's Uniform Data

Author

Carolyn W. Zhu, Mary Sano, Corbett Schimming, and Hillel Grossman

Subjects
Male, medicine.medical_specialty, Time Factors, 030209 endocrinology & metabolism, Audiology, Article, Diabetes Complications, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Memory, Risk Factors, Normal cognition, Diabetes mellitus, medicine, Humans, Dementia, Cognitive Dysfunction, Longitudinal Studies, Effects of sleep deprivation on cognitive performance, Cognitive decline, Risk factor, Psychiatry, Aged, Aged, 80 and over, Memory Disorders, business.industry, Cognition, medicine.disease, United States, Disease Progression, Female, Geriatrics and Gerontology, Alzheimer's disease, business, 030217 neurology & neurosurgery
Abstract

Background Diabetes is a risk factor for the development of cognitive impairment and possibly for accelerated progression to Alzheimer disease (AD) and other dementias, though the trajectory of cognitive decline in general and in specfic cognitive domains by diabetes is unclear. Methods Using the National Alzheimer's Coordinating Center's Uniform Data Det (NACC-UDS) to identify cohorts of elders with normal cognition (N = 7,663) and mild cognitive impairment (MCI, N = 4,114), we compared overall cognitive composite and domain specific sub-scores and their progression over time between diabetic and non-diabetic subjects. Results Diabetes was more common among those with MCI (14.7%) than among subjects who were cognitively normal (11.7%). In subjects who were cognitively normal, baseline cognitive composite scores, attention, and executive function sub-scores were lower in diabetics than non-diabetics (by 0.098, 0.066, and 0.015 points, respectively). Over time, cognitive composite score showed subtle worsening in non-diabetics (0.025 points every 6 months), with an additional worsening of 0.01 points every 6 months in diabetics compared to non-diabetics. In the MCI groups, baseline cognitive composite as well as attention and executive domain sub-scores were lower in diabetics than non-diabetics (by 0.078, 0.092, and 0.032 points, respectively). Over time, cognitive composite (by 0.103 points every 6 months) and all domain specific sub-scores showed subtle worsening in non-diabetics, but diabetics had significantly slower worsening than non-diabetics on both cognitive composite (by 0.028 points) and domain specific sub-scores. Discussion Among elders, diabetes may be associated with lower cognitive performance, primarily in non-memory domains. However it is not associated with continued worsening, suggesting a static deficit with minimal memory involvement. This data suggest that diabetes may contribute more to a vascular profile of cognitive impairment than a profile more typical of AD.

Published
2017

26. Cascaded Multi-view Canonical Correlation (CaMCCo) for Early Diagnosis of Alzheimer’s Disease via Fusion of Clinical, Imaging and Omic Features

Author

Sterling C. Johnson, Paul Malloy, Joy L. Taylor, Alan J. Lerner, Pradeep Garg, Pierre N. Tariot, David G. Clark, Steven G. Potkin, Franklin Watkins, Howard Bergman, Dana M. Pogorelec, Charles D. Smith, Pradeep Varma, Stephen Pasternack, Betty Lind, Saba Wolday, Douglas W. Scharre, Donna Munic, Marwan N. Sabbagh, Adam S. Fleisher, Joanne S. Allard, Cynthia Hunt, Lidia Glodzik, Charles Bernick, Daniel D'Agostino, Owen T. Carmichael, Geoffrey Tremont, Christopher H. van Dyck, Maria Carroll, Po Lu, Leslie Gordineer, Catherine Mc-Adams-Ortiz, Irina Rachisky, Antero Sarrael, Clifford R. Jack, David Bachman, Dick Trost, Scott Herring, Arthur W. Toga, Evan Fletcher, Christina A. Michel, Lon S. Schneider, Francine Parfitt, Kelly M. Makino, Anahita Adeli, Daniel Varon, Christine M. Belden, Nunzio Pomara, Thomas O. Obisesan, Howard Feldman, Howard Chertkow, Sandra W. Jacobson, Haibo Wang, Greg Jicha, Laura A. Flashman, George Bartzokis, Beau M. Ances, Stacy Schneider, Earl A. Zimmerman, Munir Chowdhury, Bruce L. Miller, Javier Villanueva-Meyer, Kristin Fargher, Michael W. Weiner, Dana Nguyen, Ranjan Duara, T. Y. Lee, Lisa C. Silbert, Benita Mudge, Marilyn S. Albert, James J. Lah, Janet S. Cellar, Gad A. Marshall, Michael Lin, Marc Seltzer, Leslie Shaw, Bojana Stefanovic, Daniel C. Marson, Kyle B. Womack, Liberty Teodoro, Connie Brand, Nadira Trncic, Maria Kataki, Russell H. Swerdlow, Paul S. Aisen, Brigid Reynolds, Mony J. de Leon, Sandra E. Black, Rachelle S. Doody, Paula Ogrocki, Andrew J. Saykin, Raymundo Hernando, Leyla deToledo-Morrell, Anna Burke, Sherye A. Sirrel, Henry W. Querfurth, Jeffrey R. Petrella, Norman R. Relkin, Judith L. Heidebrink, Vernice Bates, Mary L. Creech, David C. Perry, Curtis Caldwell, Sara Dolen, Anton P. Porsteinsson, Patricia Lynn Johnson, Erik D. Roberson, Effie M. Mitsis, Kathleen Johnson, John Q. Trojanowki, Raina Carter, James E. Galvin, Karen Blank, John C. Morris, Bryan M. Spann, Keith A. Johnson, Jared R. Tinklenberg, Stephen Salloway, Ronald J. Killiany, Mimi Dang, Smita Kittur, Mary Quiceno, Kaycee M. Sink, Helen Vanderswag, Erin E. Franklin, Robbartha, Kim Martin, Gaby Thai, Allyson C. Rosen, Karen L. Bell, Tracy Kendall, P. M. Doraiswamy, Kathleen Tingus, Angela Oliver, Adrian Preda, Mary L. Hynes, Laurel A. Beckett, William J. Jagust, Jeffrey M. Burns, Ronald C. Petersen, Allan I. Levey, Balebail Ashok Raj, Lawrence S. Honig, Martin R. Farlow, Richard E. Carson, Dana Mathews, David S. Knopman, Robert C. Green, Jerome A. Yesavage, Elizabeth Finger, Ann Marie Hake, David S. Geldmacher, Yaakov Stern, Raj C. Shah, M.-Marsel Mesulam, Ruth A. Mulnard, Jacobo Mintzer, Howard J. Rosen, Peggy Roberts, Joseph F. Quinn, Raymond Scott Turner, Maria T. Greig, Salvador Borges-Neto, Jeffrey Kaye, Randall Griffith, Diana R. Kerwin, Neill R. Graff-Radford, James B. Brewer, John C. Brockington, Ging-Yuek Robin Hsiung, Anant Madabhushi, Andrew E. Budson, Martha G. MacAvoy, Stephen Correia, Terence Z. Wong, Michelle Rainka, Elizabeth Oates, Alexander Norbash, Chiadi U. Onyike, Gloria Chaing, Kris Johnson, Hillel Grossman, Gary R. Conrad, Nancy Johnson, Lisa D. Ravdin, Mauricio Beccera, Reisa A. Sperling, Heather Johnson, Kristine Lipowski, Charles DeCarli, Barton Lane, Joanne L. Lord, Carl H. Sadowsky, Chris Hosein, Marissa Natelson Love, M. Ismail, Liana G. Apostolova, Dzintra Celmins, Brian R. Ott, Brittany Cerbone, Sanjay Asthana, Alice D. Brown, Neil W. Kowall, Peter A. Hardy, Andrew Kertesz, Sara S. Mason, Horacio Capote, Pauline Maillard, Stephanie Kielb, Henry Rusinek, Ellen Woo, Jeff D. Williamson, Susan De Santi, Amanda Smith, John M Olichney, Michele Assaly, Karen S. Anderson, Parianne Fatica, Brandy R. Matthews, Michael Borrie, Susan Rountree, Chuang Kuo Wu, Curtis Tatsuoka, Teresa Villena, Asha Singanamalli, Borna Bonakdarpour, Colleen S. Albers, Cynthia M. Carlsson, Bonnie S. Goldstein, Sonia Pawluczyk, Edward Coleman, Kenneth M. Spicer, Jared R. Brosch, William Brooks, Partha Sinha, Stephanie Reeder, Daniel Silverman, Robert B. Santulli, Godfrey D. Pearlson, Mark A. Mintun, and Sandra Weintraub

Subjects
0301 basic medicine, Male, Proteomics, Science, Neuroimaging, Disease, Sensitivity and Specificity, Article, 03 medical and health sciences, 0302 clinical medicine, Text mining, Alzheimer Disease, medicine, Humans, Cognitive Dysfunction, Set (psychology), Aged, Aged, 80 and over, Multidisciplinary, Modalities, business.industry, Pattern recognition, Alzheimer’s Disease Neuroimaging Initiative, Genomics, Models, Theoretical, medicine.disease, 030104 developmental biology, Categorization, Case-Control Studies, Medicine, Female, Artificial intelligence, Alzheimer's disease, business, Canonical correlation, 030217 neurology & neurosurgery, Algorithms, Biomarkers
Abstract

The introduction of mild cognitive impairment (MCI) as a diagnostic category adds to the challenges of diagnosing Alzheimer’s Disease (AD). No single marker has been proven to accurately categorize patients into their respective diagnostic groups. Thus, previous studies have attempted to develop fused predictors of AD and MCI. These studies have two main limitations. Most do not simultaneously consider all diagnostic categories and provide suboptimal fused representations using the same set of modalities for prediction of all classes. In this work, we present a combined framework, cascaded multiview canonical correlation (CaMCCo), for fusion and cascaded classification that incorporates all diagnostic categories and optimizes classification by selectively combining a subset of modalities at each level of the cascade. CaMCCo is evaluated on a data cohort comprising 149 patients for whom neurophysiological, neuroimaging, proteomic and genomic data were available. Results suggest that fusion of select modalities for each classification task outperforms (mean AUC = 0.92) fusion of all modalities (mean AUC = 0.54) and individual modalities (mean AUC = 0.90, 0.53, 0.71, 0.73, 0.62, 0.68). In addition, CaMCCo outperforms all other multi-class classification methods for MCI prediction (PPV: 0.80 vs. 0.67, 0.63).

Published
2017

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

Author

Paul S. Aisen, Sarah Walter, Kenneth M. Spicer, Stephanie Reeder, Nick C. Fox, Heather Anderson, Chuang Kuo Wu, Teresa Villena, Cynthia M. Carlsson, Paul Malloy, Bonnie S. Goldstein, Stacy Schneider, Po H. Lu, Jeffrey M. Burns, Balebail Ashok Raj, Stephanie Kielb, Adrian Preda, Pierre N. Tariot, Chet Mathis, Christopher H. van Dyck, Maria Carroll, Karen E. Smith, Lon S. Schneider, Velandai Srikanth, Daniel Varon, Nunzio Pomara, Michael Borrie, Eben S. Schwartz, Gaby Thai, Susan De Santi, Dana Nguyen, Daniel C. Marson, Gene E. Alexander, Thomas O. Obisesan, Steven Potkin, Kris A. Johnson, Henry Rusinek, Nigel J. Cairns, Gad A. Marshall, Scott C. Neu, Benita Mudge, Leyla deToledo-Morrell, Jeff D. Williamson, Helen Vanderswag, Howard Chertkow, Sandra W. Jacobson, Dana Mathews, Arthur W. Toga, Saba Wolday, Douglas W. Scharre, Lidia Glodzik, Rob Bartha, Anders M. Dale, Norbert Schuff, Ging-Yuek Robin Hsiung, Rachelle S. Doody, Richard D. King, Vernice Bates, Li Shen, Barton Lane, Kristin Fargher, Chris Moran, Greg Jicha, Dan Bandy, Sara Dolen, Andrew E. Budson, Martha G. MacAvoy, Daniel H.S. Silverman, Anton P. Porsteinsson, Kathleen R. Johnson, Michele L. Callisaya, Betty Lind, Michael D. Devous, Robert C. Green, P. Murali Doraiswamy, Andrew J. Saykin, Joseph F. Quinn, Kristina Lipowski, Raymundo Hernando, Catherine Mc-Adams-Ortiz, Ronald G. Thomas, Jeffrey Kaye, Irina Rachinsky, Donna Munic, Munir Chowdhury, Bruce L. Miller, Les Shaw, Brian R. Ott, Randall Griffith, Kristen Martin-Cook, Marwan N. Sabbagh, Crystal V. Flynn Longmire, Raymond Scott Turner, Karen Blank, Effie M. Mitsis, Charles Bernick, Marilyn S. Albert, John M Olichney, Earl A. Zimmerman, Jared R. Tinklenberg, Robert A. Koeppe, Dick Trost, Howard Feldman, Laura L. Boles Ponto, M. Saleem Ismail, Alan J. Lerner, Kelly M. Makino, Pradeep Garg, Jeffrey R. Petrella, Peter J. Snyder, Norman R. Relkin, Laurel A. Beckett, Allyson C. Rosen, Devon Gessert, MaryAnn Oakley, J. Q. Trojanowki, Lisa Raudin, Stephen Salloway, Paula Ogrocki, Bryan M. Spann, Susan K. Schultz, Adam S. Fleisher, Brigid Reynolds, Jason Karlawish, Michele Assaly, John Q. Trojanowki, Kewei Chen, Enchi Liu, Mary Quiceno, Kaycee M. Sink, Jerome A. Yesavage, Sterling C. Johnson, Curtis B. Caldwell, Heather E. Johnson, Neill R. Graff-Radford, Karen S. Anderson, Richard Frank, John C. Morris, Donna M. Simpson, Tatiana Foroud, Joel P. Felmlee, Zaven Kachaturian, Magdalena Korecka, George Bartzokis, Francine Parfitt, Henry W. Querfurth, Patricia Lynn Johnson, Raj C. Shah, M.-Marsel Mesulam, Howard J. Rosen, Ann Marie Hake, Danielle J Harvey, Hyungsub Shim, Dick J. Drost, Yaakov Stern, Charles DeCarli, Brandy R. Matthews, Geoffrey Tremont, Kim Martin, Robert B. Santulli, Aliza Romirowsky, Joy L. Taylor, Ramon Diaz-Arrastia, Godfrey D. Pearlson, Mark A. Mintun, James J. Lah, Norm Foster, Matt A. Bernstein, Diana R. Kerwin, Virginia M.-Y. Lee, Bojana Stefanovic, Joanne L. Lord, Chris Hosein, Susan E. Molchan, David J. Clark, Leon Hudson, Janet S. Cellar, Karen Crawford, Richard Beare, Franklin Watkins, T. J. Montine, Ronald C. Petersen, Carl H. Sadowsky, David A. Wolk, Steven E. Arnold, Nancy Collins Johnson, Ruth A. Mulnard, Antero Sarrael, John Kornak, Amanda Smith, Owen Carmichael, Beau M. Ances, Clifford R. Jack, Meghan Frey, Martin R. Farlow, William J. Jagust, Ronald J. Killiany, Mony J. de Leon, Sandra E. Black, Javier Villanueva-Meyer, Smita Kittur, Walter Martinez, Sue Leon, Anthony Gamst, James B. Brewer, Hillel Grossman, Eric M. Reiman, Jacobo Mintzer, Stephen Correia, Kyle B. Womack, Maria Kataki, Lawrence S. Honig, Liana G. Apostolova, Peggy Roberts, Christine Belden, Michelle Rainka, Alexander Norbash, R. Edward Coleman, Richard E. Carson, Dzintra Celmins, Lisa Taylor-Reinwald, Scott Herring, Oscar L. Lopez, Michael W. Weiner, Ranjan Duara, Elizabether Finger, Peter A. Hardy, Myron F. Weiner, Horacio Capote, Keith A. Johnson, Karen L. Bell, Allan I. Levey, Steven G. Potkin, Howard Bergman, John A. Rogers, Wei Wang, Connie Brand, Chiadi U. Onyike, Paul M. Thompson, Russell H. Swerdlow, Gloria Chaing, Judith L. Heidebrink, Salome K. Bwayo, Reisa A. Sperling, Michael C. Donohue, Sanjay Asthana, Alice D. Brown, Charles D. Smith, Neil W. Kowall, Andrew Kertesz, Tamie Sather, Evan Fletcher, and Sonia Pawluczyk

Subjects
Blood Glucose, Male, Pediatrics, medicine.medical_specialty, endocrine system diseases, Article, Alzheimer Disease, medicine, Dementia, Humans, Cognitive Dysfunction, Longitudinal Studies, Cognitive decline, Cognitive reserve, Aged, Aged, 80 and over, Cerebral Cortex, business.industry, Type 2 Diabetes Mellitus, nutritional and metabolic diseases, Brain, Cognition, Organ Size, medicine.disease, Magnetic Resonance Imaging, Cognitive test, Diabetes Mellitus, Type 2, Cohort, Female, Neurology (clinical), Alzheimer's disease, Atrophy, business, Factor Analysis, Statistical
Abstract

ObjectiveTo study longitudinal relationships between type 2 diabetes mellitus (T2DM), cortical thickness, and cognitive function in older people with normal cognition, mild cognitive impairment, and Alzheimer disease (AD).MethodsThe sample was derived from the Alzheimer's Disease Neuroimaging Initiative cohort who underwent brain MRI and cognitive tests annually for 5 years. Presence of T2DM was based on fasting blood glucose ≥7.0mml/L or the use of glucose-lowering agents. We used latent growth curve modeling to explore longitudinal relationships between T2DM, cortical thickness, and cognitive function, adjusting for relevant covariates and testing for interactions.ResultsThere were 124 people with T2DM (mean age 75.5 years, SD 6.2) and 693 without T2DM (mean age 75.1 years, SD 6.9) with at least 1 MRI available. AD and lower cortical thickness at study entry was associated with a lower chance of having a MRI available at each follow-up phase (all p < 0.001). T2DM was associated with lower baseline cortical thickness (p = 0.01). We found no direct effect of T2DM on decline in cortical thickness or cognitive function, but there was an indirect pathway linking T2DM and cognitive decline via baseline cortical thickness (β = −0.17, p = 0.022). There was an interaction between T2DM and education whereby the negative effect of T2DM on baseline cortical thickness was reduced in those with greater education (β = 0.34, p = 0.037). These associations changed minimally when adjusted for baseline cognitive diagnosis.ConclusionsIn an older cohort with low cerebrovascular disease burden, T2DM contributes to cognitive decline via neurodegeneration. Prior brain and cognitive reserve may protect against this effect.

Published
2018

28. Brain multiplexes reveal morphological connectional biomarkers fingerprinting late brain dementia states

Author

Jerome A. Yesavage, Thomas O. Obisesan, Ann Marie Hake, Yaakov Stern, Betty Lind, Daniel D'Agostino, Daniel Varon, Christine M. Belden, Evan Fletcher, Jef Williamson, Howard Feldman, Pauline Maillard, Stephanie Kielb, Dana Mathews, Henry Rusinek, Sonia Pawluczyk, Donna Munic, Michele Assaly, Ines Mahjoub, Barton Lane, Andrew J. Saykin, Raymundo Hernando, Randall Grifth, Paul S. Aisen, Brittany Cerbone, Saba Wolday, Douglas W. Scharre, Karen S. Anderson, Sara S. Mason, Marwan N. Sabbagh, Geofrey Tremont, Stacy Schneider, Marilyn S. Albert, Tracy Kendall, P. M. Doraiswamy, Antero Sarrael, Kenneth M. Spicer, George Bartzokis, Parianne Fatica, Christopher H. van Dyck, Maria Carroll, Benita Mudge, Beau M. Ances, Brandy R. Matthews, Allyson C. Rosen, Chiadi U. Onyike, Gloria Chaing, Helen Vanderswag, Javier Villanueva-Meyer, Stephanie Reeder, Erin E. Franklin, Sandra Weintraub, Liberty Teodoro, Connie Brand, Arthur W. Toga, Mony J. de Leon, Sandra E. Black, Robert C. Green, Russell H. Swerdlow, Leyla deToledo-Morrell, Bryan M. Spann, Judith L. Heidebrink, Leslie Shaw, Ruth A. Mulnard, Rob Bartha, Sterling C. Johnson, Kristin Fargher, Susan De Santi, Curtis Caldwell, Rachelle S. Doody, Erik D. Roberson, Norman R. Relkin, Kathleen Johnson, Raj C. Shah, Kris Johnson, Diana Kerwin, M.-Marsel Mesulam, Howard J. Rosen, Peggy Roberts, Michael Borrie, Martin R. Farlow, Steven G. Potkin, Reisa A. Sperling, John Q. Trojanowki, Amanda Smith, James J. Lah, Mary L. Creech, Janet S. Cellar, Michael Lin, Terence Z. Wong, Howard Bergman, Dana M. Pogorelec, Gaby Thai, Jacobo Mintzer, Raina Carter, Heather Johnson, Francine Parftt, Karen Blank, Daniel C. Marson, Nancy Johnson, Susan Rountree, Michelle Rainka, Elizabeth Oates, Stephen Correia, John C. Morris, Alan J. Lerner, Pradeep Garg, Mauricio Beccera, Mary L. Hynes, Chuang Kuo Wu, Curtis Tatsuoka, Brian R. Ott, Joy L. Taylor, Mohamed Ali Mahjoub, Adrian Preda, Islem Rekik, Ronald C. Petersen, Kathleen Tingus, Vernice Bates, Irina Rachisky, Neill Graf-Radford, Alexander Norbash, Teresa Villena, Paul Malloy, Cliford Jack, Pierre N. Tariot, Anton P. Porsteinsson, Jefrey Burns, Owen Carmichael, Maria T. Greig, Marc Seltzer, Pradeep Varma, Jefrey Petrella, James E. Galvin, Joseph F. Quinn, Franklin Watkins, John M Olichney, Joanne L. Lord, Raymond Scott Turner, Adam S. Fleisher, Salvador Borges-Neto, James B. Brewer, Carl H. Sadowsky, Andrew E. Budson, Martha G. MacAvoy, Joanne S. Allard, L. Schneider, Stephen Salloway, Kim Martin, Mary Quiceno, Kaycee M. Sink, Sanjay Asthana, Laurel A. Beckett, Alice D. Brown, David S. Knopman, Neil W. Kowall, Efe Mitsis, Elizabeth Finger, David C. Perry, Bojana Stefanovic, David S. Geldmacher, Andrew Kertesz, Cynthia M. Carlsson, Charles Bernick, Earl A. Zimmerman, Bonnie S. Goldstein, Dzintra Celmins, Paula Ogrocki, Daniel H.S. Silverman, David G. Clark, Charles D. Smith, Nunzio Pomara, Stephen Pasternack, Howard Chertkow, Christina A. Michel, Sandra W. Jacobson, Po Lu, Peter A. Hardy, Greg Jicha, David Bachman, Laura A. Flashman, Munir Chowdhury, Bruce L. Miller, Ging Yuek Robin Hsiung, Horacio Capote, Gad A. Marshall, Brigid Reynolds, Jefrey Kaye, Patricia Lynn Johnson, Ronald J. Killiany, Mimi Dang, Smita Kittur, Lawrence S. Honig, Ranjan Duara, T. Y. Lee, Keith A. Johnson, Karen L. Bell, Allan I. Levey, Scott Herring, Michael W. Weiner, Ellen Woo, Dana Nguyen, Robert B. Santulli, Godfrey D. Pearlson, Mark A. Mintun, Sara Dolen, Jared R. Tinklenberg, Edward Coleman, Jared R. Brosch, John C. Brockington, William Brooks, Partha Sinha, M. Ismail, Balebail Ashok Raj, Lisa D. Ravdin, Kristine Lipowski, Charles DeCarli, Borna Bonakdarpour, Colleen S. Albers, Chris Hosein, Marissa Natelson Love, Kyle B. Womack, Maria Kataki, Nadira Trncic, Anna Burke, Sherye A. Sirrel, Henry W. Querfurth, Liana G. Apostolova, Angela Oliver, William J. Jagust, Richard E. Carson, Cynthia Hunt, Lidia Glodzik, Hillel Grossman, Gary R. Conrad, Leslie Gordineer, Catherine Mc-Adams-Ortiz, Dick Trost, Kelly M. Makino, Anahita Adeli, and Lisa C. Silbert

Subjects
Right entorhinal cortex, Models, Neurological, lcsh:Medicine, Biology, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, medicine, Humans, Middle frontal gyrus, Dementia, Patient treatment, lcsh:Science, Cognitive impairment, Multidisciplinary, Extramural, lcsh:R, Brain, Diagnostic marker, Alzheimer’s Disease Neuroimaging Initiative, medicine.disease, Magnetic Resonance Imaging, Brain region, lcsh:Q, Cognition Disorders, Neuroscience, Biomarkers, 030217 neurology & neurosurgery
Abstract

Accurate diagnosis of mild cognitive impairment (MCI) before conversion to Alzheimer’s disease (AD) is invaluable for patient treatment. Many works showed that MCI and AD affect functional and structural connections between brain regions as well as the shape of cortical regions. However, ‘shape connections’ between brain regions are rarely investigated -e.g., how morphological attributes such as cortical thickness and sulcal depth of a specific brain region change in relation to morphological attributes in other regions. To fill this gap, we unprecedentedly design morphological brain multiplexes for late MCI/AD classification. Specifically, we use structural T1-w MRI to define morphological brain networks, each quantifying similarity in morphology between different cortical regions for a specific cortical attribute. Then, we define a brain multiplex where each intra-layer represents the morphological connectivity network of a specific cortical attribute, and each inter-layer encodes the similarity between two consecutive intra-layers. A significant performance gain is achieved when using the multiplex architecture in comparison to other conventional network analysis architectures. We also leverage this architecture to discover morphological connectional biomarkers fingerprinting the difference between late MCI and AD stages, which included the right entorhinal cortex and right caudal middle frontal gyrus.

Published
2018

29. P1-547: MAILING OUTREACH FOR PARTICIPATION IN COGNITIVE IMPAIRMENT AND ALZHEIMER'S DISEASE RESEARCH

Author

Michael T Kinsella, Margaret Sewell, Nelly Velasco, Hillel Grossman, Judith Neugroschl, Clara Li, Jason Bayus, Carolyn W. Zhu, Mary Sano, and Kelly Pun

Subjects
Gerontology, Epidemiology, business.industry, Health Policy, Outreach, Alzheimer's disease research, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Medicine, Neurology (clinical), Geriatrics and Gerontology, business, Cognitive impairment
Published
2019

30. [P1–502]: NON‐AMNESTIC DEFICIT CHARACTERIZES THE COGNITIVE PROFILE IN DIABETES: RESULTS FROM NATIONAL ALZHEIMER'S COORDINATING CENTER'S UNIFORM DATA SET (NACC UDS)

Author

Hillel Grossman, Corbett Schimming, Mary Sano, and Carolyn W. Zhu

Subjects
030214 geriatrics, Epidemiology, Health Policy, 030508 substance abuse, Cognition, medicine.disease, Data set, 03 medical and health sciences, Psychiatry and Mental health, Cellular and Molecular Neuroscience, 0302 clinical medicine, Developmental Neuroscience, Diabetes mellitus, medicine, Center (algebra and category theory), Neurology (clinical), Geriatrics and Gerontology, 0305 other medical science, Psychology, Cognitive psychology
Published
2017

31. Pattern Discovery in Brain Imaging Genetics via SCCA Modeling with a Generic Non-convex Penalty

Author

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

Subjects
0301 basic medicine, Male, lcsh:Medicine, Feature selection, Neuroimaging, Biology, Polymorphism, Single Nucleotide, Article, Pattern Recognition, Automated, Correlation, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Feature (machine learning), Image Processing, Computer-Assisted, Humans, lcsh:Science, Aged, Genetics, Computational model, Multidisciplinary, Models, Statistical, lcsh:R, Alzheimer’s Disease Neuroimaging Initiative, Regression, body regions, 030104 developmental biology, Phenotype, Pattern recognition (psychology), Multivariate Analysis, lcsh:Q, Female, Canonical correlation, 030217 neurology & neurosurgery, Algorithms, Alzheimer's Disease Neuroimaging Initiative
Abstract

Brain imaging genetics intends to uncover associations between genetic markers and neuroimaging quantitative traits. Sparse canonical correlation analysis (SCCA) can discover bi-multivariate associations and select relevant features, and is becoming popular in imaging genetic studies. The L1-norm function is not only convex, but also singular at the origin, which is a necessary condition for sparsity. Thus most SCCA methods impose $${\ell }_{{\bf{1}}}$$ ℓ 1 -norm onto the individual feature or the structure level of features to pursuit corresponding sparsity. However, the $${\ell }_{{\bf{1}}}$$ ℓ 1 -norm penalty over-penalizes large coefficients and may incurs estimation bias. A number of non-convex penalties are proposed to reduce the estimation bias in regression tasks. But using them in SCCA remains largely unexplored. In this paper, we design a unified non-convex SCCA model, based on seven non-convex functions, for unbiased estimation and stable feature selection simultaneously. We also propose an efficient optimization algorithm. The proposed method obtains both higher correlation coefficients and better canonical loading patterns. Specifically, these SCCA methods with non-convex penalties discover a strong association between the APOE e4 rs429358 SNP and the hippocampus region of the brain. They both are Alzheimer’s disease related biomarkers, indicating the potential and power of the non-convex methods in brain imaging genetics.

Published
2017

32. Longitudinal measurement and hierarchical classification framework for the prediction of Alzheimer's disease

Author

Mary L. Hynes, Liberty Teodoro, John C. Brockington, Connie Brand, Paul Malloy, Russell H. Swerdlow, Ronald C. Petersen, Judith L. Heidebrink, Pierre N. Tariot, Curtis Caldwell, Clifford R. Jack, David G. Clark, Neill R. Graff-Radford, Charles D. Smith, Geoffrey Tremont, Ranjan Duara, Stephen Pasternack, T. Y. Lee, Owen Carmichael, Nadira Trncic, Irina Rachisky, Daniel D'Agostino, James J. Lah, Steven G. Potkin, Howard Bergman, Dana M. Pogorelec, Lon S. Schneider, Anna Burke, Sherye A. Sirrel, Henry W. Querfurth, Michael Lin, David Bachman, Edward Coleman, Michele Assaly, Allyson C. Rosen, Jeffrey M. Burns, Balebail Ashok Raj, Jared R. Brosch, Joanne L. Lord, William Brooks, Brigid Reynolds, Karen S. Anderson, Sandra Jacobson, Nunzio Pomara, Patricia Lynn Johnson, George Bartzokis, Parianne Fatica, Benita Mudge, Dana Nguyen, Carl H. Sadowsky, Michael Borrie, Qianjin Feng, Chiadi U. Onyike, Partha Sinha, Gloria Chaing, Howard Chertkow, Leyla deToledo-Morrell, Bojana Stefanovic, Richard E. Carson, Wufan Chen, Ronald J. Killiany, Mimi Dang, Thomas O. Obisesan, Christopher H. van Dyck, Maria Carroll, Gaby Thai, Arthur W. Toga, Chuang Kuo Wu, Erik D. Roberson, Effie M. Mitsis, Smita Kittur, Keith A. Johnson, Dana Mathews, Sara Dolen, Raj C. Shah, M.-Marsel Mesulam, Howard J. Rosen, Karen L. Bell, Ging-Yuek Robin Hsiung, Teresa Villena, Kris Johnson, Saba Wolday, Douglas W. Scharre, Kyle B. Womack, Maria Kataki, Barton Lane, Angela Oliver, Greg Jicha, Reisa A. Sperling, Wei Yang, David S. Geldmacher, Lawrence S. Honig, Sanjay Asthana, Janet S. Cellar, William J. Jagust, Dzintra Celmins, Susan Rountree, Christina A. Michel, Allan I. Levey, Tracy Kendall, Lisa D. Ravdin, Jared R. Tinklenberg, Brittany Cerbone, Alice D. Brown, Marilyn S. Albert, Andrew J. Saykin, Raymundo Hernando, Sandra Weintraub, John Q. Trojanowki, Raina Carter, Betty Lind, Kristin Fargher, Sterling C. Johnson, P. Murali Doraiswamy, Jeffrey R. Petrella, Neil W. Kowall, Sara S. Mason, Heather Johnson, Mary L. Creech, Stacy Schneider, Donna Munic, Liana G. Apostolova, Peter A. Hardy, Munir Chowdhury, Bruce L. Miller, Ruth A. Mulnard, Curtis Tatsuoka, Po H. Lu, Daniel C. Marson, Pauline Maillard, John C. Morris, Marwan N. Sabbagh, Jeffrey Kaye, Hillel Grossman, Gary R. Conrad, Karen Blank, Meiyan Huang, Stephanie Kielb, Andrew Kertesz, Jerome A. Yesavage, Leslie Shaw, Martin R. Farlow, Maria T. Greig, Jacobo Mintzer, Susan De Santi, David S. Knopman, Marc Seltzer, Scott Herring, Joy L. Taylor, Vernice Bates, Rob Bartha, Cynthia Hunt, Henry Rusinek, Randall Griffith, Cynthia M. Carlsson, Charles Bernick, Bonnie S. Goldstein, Rachelle S. Doody, Leslie Gordineer, Catherine Mc-Adams-Ortiz, Kim Martin, Howard Feldman, David C. Perry, Horacio Capote, Lidia Glodzik, Stephen Correia, James B. Brewer, Elizabeth Finger, Jeff D. Williamson, Franklin Watkins, Borna Bonakdarpour, Colleen S. Albers, M. Saleem Ismail, Alan J. Lerner, Daniel Varon, Christine M. Belden, Sonia Pawluczyk, Paul S. Aisen, Pradeep Garg, Kelly M. Makino, Laurel A. Beckett, Peggy Roberts, Nancy Johnson, Anahita Adeli, Terence Z. Wong, Michelle Rainka, Elizabeth Oates, Amanda Smith, Kenneth M. Spicer, Laura A. Flashman, Kristine Lipowski, Charles DeCarli, Stephanie Reeder, Mauricio Beccera, Dick Trost, Alexander Norbash, Lisa C. Silbert, Michael W. Weiner, Gad A. Marshall, Ann Marie Hake, Pradeep Varma, Francine Parfitt, Chris Hosein, Adam S. Fleisher, Marissa Natelson Love, Joanne S. Allard, Earl A. Zimmerman, Kathleen Tingus, Brian R. Ott, Joseph F. Quinn, Anton P. Porsteinsson, Paula Ogrocki, Raymond Scott Turner, Salvador Borges-Neto, James E. Galvin, Yaakov Stern, Andrew E. Budson, Martha G. MacAvoy, Daniel H.S. Silverman, Robert B. Santulli, Adrian Preda, Godfrey D. Pearlson, Mark A. Mintun, Stephen Salloway, Mary Quiceno, Kaycee M. Sink, John M Olichney, Antero Sarrael, Beau M. Ances, Javier Villanueva-Meyer, Mony J. de Leon, Sandra E. Black, Bryan M. Spann, Diana R. Kerwin, Ellen Woo, Helen Vanderswag, Erin E. Franklin, Robert C. Green, and Norman R. Relkin

Subjects
Male, Computer science, Neuroimaging, Disease, computer.software_genre, Sensitivity and Specificity, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Predictive Value of Tests, mental disorders, medicine, Dementia, Humans, Cognitive Dysfunction, Longitudinal Studies, Cognitive impairment, Aged, Aged, 80 and over, Multidisciplinary, medicine.diagnostic_test, business.industry, Brain, Pattern recognition, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Early Diagnosis, Disease Progression, Female, Data mining, Artificial intelligence, business, computer, 030217 neurology & neurosurgery, Alzheimer's Disease Neuroimaging Initiative, Follow-Up Studies
Abstract

Accurate prediction of Alzheimer’s disease (AD) is important for the early diagnosis and treatment of this condition. Mild cognitive impairment (MCI) is an early stage of AD. Therefore, patients with MCI who are at high risk of fully developing AD should be identified to accurately predict AD. However, the relationship between brain images and AD is difficult to construct because of the complex characteristics of neuroimaging data. To address this problem, we present a longitudinal measurement of MCI brain images and a hierarchical classification method for AD prediction. Longitudinal images obtained from individuals with MCI were investigated to acquire important information on the longitudinal changes, which can be used to classify MCI subjects as either MCI conversion (MCIc) or MCI non-conversion (MCInc) individuals. Moreover, a hierarchical framework was introduced to the classifier to manage high feature dimensionality issues and incorporate spatial information for improving the prediction accuracy. The proposed method was evaluated using 131 patients with MCI (70 MCIc and 61 MCInc) based on MRI scans taken at different time points. Results showed that the proposed method achieved 79.4% accuracy for the classification of MCIc versus MCInc, thereby demonstrating very promising performance for AD prediction.

Published
2017

33. Palliative Care as a Primary Therapeutic Approach in Advanced Dementia: A Narrative Review

Author

Hillel Grossman and Erin K. Zahradnik

Subjects
Pharmacology, Geriatrics, medicine.medical_specialty, Palliative care, business.industry, Palliative Care, Cognition, medicine.disease, Therapeutic approach, Nursing, Quality of life, mental disorders, Quality of Life, medicine, Humans, Dementia, Pharmacology (medical), Intensive care medicine, business, Curative care, Geriatric psychiatry
Abstract

Purpose The goal of this narrative review was to identify and summarize the ways in which palliative care could benefit patients who have advanced dementia. Methods This case-based discussion article examines current literature on palliative care for dementia. Findings Dementia is an incurable, progressive disease that affects millions of subjects. The prevalence has grown in the last decade and is projected to continue on this trajectory. In the later stages of dementia, subjects require increasing levels of care due to severe cognitive and functional impairment. Although the field of palliative medicine focuses on improving the quality of life of patients with life-limiting illnesses, many patients with advanced dementia do not receive palliative care services. Implications Palliative care has been shown to improve patient and caregiver satisfaction, quality of life, and symptom burden at the end of life. Patients with advanced dementia would benefit from increased access to palliative care.

Published
2014

34. P1-471: THE UTILITY OF VERBAL MEMORY TESTS AS SENSITIVE MARKERS FOR EARLY-STAGE ALZHEIMER'S DISEASE IN ELDERLY CHINESE AMERICANS

Author

Margaret Sewell, Hillel Grossman, Mari Umpierre, Mary Sano, QiYing Huang, Judith Neugroschl, Clara Li, Xiaoyi Zeng, Jane Martin, Dongming Cai, and Carolyn W. Zhu

Subjects
Epidemiology, business.industry, Health Policy, Disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Medicine, Neurology (clinical), Geriatrics and Gerontology, Stage (cooking), Verbal memory, business, Clinical psychology, Chinese americans
Published
2019

35. Basal forebrain degeneration precedes and predicts the cortical spread of Alzheimer's pathology

Author

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

Subjects
0301 basic medicine, Male, Pathology, medicine.medical_specialty, Amyloid, Basal Forebrain, Science, General Physics and Astronomy, Degeneration (medical), Grey matter, General Biochemistry, Genetics and Molecular Biology, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, medicine, Entorhinal Cortex, Humans, Aged, Aged, 80 and over, Basal forebrain, Multidisciplinary, Amyloid beta-Peptides, business.industry, General Chemistry, medicine.disease, Entorhinal cortex, Prognosis, Magnetic Resonance Imaging, 030104 developmental biology, medicine.anatomical_structure, Biomarker (medicine), Female, Alzheimer's disease, business, 030217 neurology & neurosurgery, Biomarkers, Alzheimer's Disease Neuroimaging Initiative
Abstract

There is considerable debate whether Alzheimer's disease (AD) originates in basal forebrain or entorhinal cortex. Here we examined whether longitudinal decreases in basal forebrain and entorhinal cortex grey matter volume were interdependent and sequential. In a large cohort of age-matched older adults ranging from cognitively normal to AD, we demonstrate that basal forebrain volume predicts longitudinal entorhinal degeneration. Models of parallel degeneration or entorhinal origin received negligible support. We then integrated volumetric measures with an amyloid biomarker sensitive to pre-symptomatic AD pathology. Comparison between cognitively matched normal adult subgroups, delineated according to the amyloid biomarker, revealed abnormal degeneration in basal forebrain, but not entorhinal cortex. Abnormal degeneration in both basal forebrain and entorhinal cortex was only observed among prodromal (mildly amnestic) individuals. We provide evidence that basal forebrain pathology precedes and predicts both entorhinal pathology and memory impairment, challenging the widely held belief that AD has a cortical origin., Whether Alzheimer's disease originates in basal forebrain or entorhinal cortex remains highly debated. Here the authors use structural magnetic resonance data from a longitudinal sample of participants stratified by cerebrospinal biomarker and clinical diagnosis to show that tissue volume changes appear earlier in the basal forebrain than in the entorhinal cortex.

Published
2016

36. Cognition in Non-Demented Diabetic Older Adults

Author

Xiaodong Luo, Mary Sano, Hillel Grossman, Sirisha Nandipati, and Corbett Schimming

Subjects
Male, Pulmonary and Respiratory Medicine, Gerontology, Aging, Longitudinal study, medicine.medical_specialty, Disease, Neuropsychological Tests, Risk Assessment, Article, Executive Function, Cognition, Memory, Risk Factors, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, Cognitive decline, Psychiatry, Aged, Language, Retrospective Studies, Aged, 80 and over, Psychomotor function, Chi-Square Distribution, Age Factors, Neuropsychology, Middle Aged, medicine.disease, United States, Diabetes Mellitus, Type 1, Pediatrics, Perinatology and Child Health, Linear Models, Female, Cognition Disorders, Psychology, Chi-squared distribution, Psychomotor Performance
Abstract

Evidence links diabetes mellitus to cognitive impairment and increased risk of Alzheimer's disease (AD) and suggests that insulin therapy improves cognition. With an increasing percentage of the US elderly population at high risk for diabetes and AD, the evidence of an association between diabetes and poor cognition in non-demented elderly may have implications for diagnosis, prevention and treatment of cognitive decline including AD. In our study, we hypothesized that diabetic elders with normal cognition would demonstrate poorer cognitive outcomes than non-diabetic elders and that diabetic elders receiving diabetes treatment would demonstrate better outcomes than those not receiving treatment. Data were evaluated from the National Alzheimer's Coordinating Center's Uniform Data Set (UDS). The UDS consists of clinical and neuropsychological assessments of a sample of elderly research subjects recruited from thirty-one Alzheimer's Disease Centers nationwide. The UDS provides a unique opportunity to study cognition in a nationally recruited sample with structured neuropsychological tests. We examined the impact of diabetes and diabetes treatment on cognitive measures in 3421 elderly research subjects from 2005-2007 with normal cognition. We performed linear regression analyses to compare cognitive scores between diabetic subjects and non-diabetic subjects. Diabetic subjects had lower scores than non-diabetic subjects including attention, psychomotor function and executive function, but no differences in memory or semantic memory language. There was no association between diabetes treatment and cognitive scores. These subtle but significant cognitive deficits in diabetic subjects compared to non-diabetic subjects may contribute to difficulty with compliance with complex diabetes medication regimens. A specific role of diabetes as a risk for cognitive impairment will require longitudinal study.

Published
2012

37. Hypertension is Associated With Cognitive Decline in Elderly People at High Risk for Dementia

Author

Michael Wysocki, Michal Schnaider Beeri, Vahram Haroutunian, James Schmeidler, Xiaodong Luo, Gerson T. Lesser, Karen Dahlman, and Hillel Grossman

Subjects
Male, Gerontology, medicine.medical_specialty, Cardiovascular risk factors, Article, Cohort Studies, Alzheimer Disease, Risk Factors, mental disorders, medicine, Humans, Dementia, Elderly people, Cognitive Dysfunction, Cognitive decline, Psychiatry, Aged, Aged, 80 and over, Cognition, Prognosis, medicine.disease, Psychiatry and Mental health, Increased risk, Hypertension, Female, Geriatrics and Gerontology, Alzheimer's disease, Cognition Disorders, Psychology, Cohort study
Abstract

Cardiovascular risk factors including hypertension (HTN) have been shown to increase the risk of Alzheimer disease. The current study investigated whether individuals with HTN are more susceptible to increased cognitive decline and whether the influence of HTN on cognitive decline varied as a function of dementia severity. A total of 224 nursing home and assisted living residents, with a mean age of 84.9 (±7.6) years, were assessed longitudinally with Mini Mental State Exams (MMSEs) and Clinical Dementia Ratings (CDR). Baseline dementia status was defined by the CDR score. As described in Table 2, MMSE scores in persons with HTN and questionable dementia (CDR = 0.5) declined significantly faster than nonhypertensive questionably demented persons. Hypertensive participants did not decline significantly faster than nonhypertensive participants in persons with intact cognition (CDR = 0) or frank dementia (CDR ≥ 1). These results suggest an increased risk of subsequent cognitive decline in hypertensive individuals who are especially vulnerable to developing dementia and raises the possibility that avoiding or controlling HTN might reduce the rate of cognitive decline in cognitively vulnerable individuals, potentially delaying their conversion to full-fledged dementia.

Published
2012

38. The MMSE orientation for time domain is a strong predictor of subsequent cognitive decline in the elderly

Author

Elizabeth Guerrero-Berroa, Michael A. Rapp, Vahram Haroutunian, Michal Schnaider Beeri, Karen Dahlman, James Schmeidler, Xiaodong Luo, and Hillel Grossman

Subjects
Male, Gerontology, Aging, medicine.medical_specialty, Psychometrics, Neuropsychological Tests, Audiology, Article, Predictive Value of Tests, Orientation (mental), mental disorders, medicine, Humans, Dementia, Cognitive decline, Geriatric Assessment, Aged, Aged, 80 and over, medicine.diagnostic_test, Cognitive disorder, Cognition, Neuropsychological test, Middle Aged, medicine.disease, Nursing Homes, Psychiatry and Mental health, Mental Recall, Disease Progression, Linear Models, Female, Geriatrics and Gerontology, Alzheimer's disease, Cognition Disorders, Psychology
Abstract

Background The mini-mental state exam (MMSE) has been used to address questions such as determination of appropriate cutoff scores for differentiation of individuals with intact cognitive function from patients with dementia and rate of cognitive decline. However, little is known about the relationship of performance in specific cognitive domains to subsequent overall decline. Objective To examine the specific and/or combined contribution of four MMSE domains (orientation for time, orientation for place, delayed recall, and attention) to prediction of overall cognitive decline on the MMSE. Methods Linear mixed models were applied to 505 elderly nursing home residents (mean age = 85, > 12 years education = 27%; 79% F, mean follow-up = 3.20 years) to examine the relationship between baseline scores of these domains and total MMSE scores over time. Results Orientation for time was the only domain significantly associated with MMSE decline over time. Combination of poor delayed recall with either attention or orientation for place was associated with significantly increased decline on the MMSE. Conclusions The MMSE orientation for time predicts overall decline on MMSE scores over time. A good functioning domain added to good functioning delayed recall was associated with slower rate of decline. Copyright © 2009 John Wiley & Sons, Ltd.

Published
2009

39. C-reactive protein and memory function suggest antagonistic pleiotropy in very old nondemented subjects

Author

Jeremy M. Silverman, Gregory A. Elder, Hillel Grossman, Michal Schnaider Beeri, James Schmeidler, Clive Rosendorff, Rizalina Mavris, Gary Angelo, Rebecca K. West, and José R. Carrión-Baralt

Subjects
Male, Gerontology, Aging, medicine.medical_specialty, Cross-sectional study, Inflammation, Cognition, Memory, Pleiotropy, Internal medicine, medicine, Humans, Dementia, Cognitive skill, Aged, Aged, 80 and over, Psychiatric Status Rating Scales, biology, business.industry, C-reactive protein, Healthy subjects, General Medicine, medicine.disease, Research Letters, C-Reactive Protein, Cross-Sectional Studies, Endocrinology, biology.protein, Female, Geriatrics and Gerontology, medicine.symptom, business
Abstract

SIR—A possible role of inflammation in the development of dementia [1] has led to investigations examining whether C-reactive protein (CRP), a systemic marker of inflammation, is associated with worse cognitive function and decline in old age. Elevated CRP has been associated with worse global and specific cognitive functioning [2–7], although other studies have found no relationship between CRP and cognition [8–10]. Most studies have examined samples averaging

Published
2008

40. Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathology

Author

Jeremy M. Silverman, Dushyant P. Purohit, Christine Hannigan, Sam Gandy, Michael Wysocki, Michal Schnaider Beeri, James Schmeidler, Hillel Grossman, Vahram Haroutunian, and Gerson T. Lesser

Subjects
Male, medicine.medical_specialty, Postmortem studies, Clinical Dementia Rating, medicine.medical_treatment, Plaque, Amyloid, Neuropathology, Severity of Illness Index, Internal medicine, Diabetes mellitus, Diabetes Mellitus, medicine, Humans, Hypoglycemic Agents, Insulin, Dementia, Aged, Aged, 80 and over, Psychiatric Status Rating Scales, Analysis of Variance, business.industry, Brain, Neurofibrillary Tangles, Articles, medicine.disease, Entorhinal cortex, Endocrinology, Case-Control Studies, Postmortem Changes, Drug Therapy, Combination, Female, Neurology (clinical), Alzheimer's disease, business
Abstract

Objective: To examine the association between treatment for diabetes and Alzheimer disease (AD) neuropathology. Methods: This postmortem study matched 124 subjects with diabetes to 124 without diabetes from the Mount Sinai School of Medicine Brain Bank, on age (mean = 81.2 + 9.3), sex (57.3% F), and severity of dementia (Clinical Dementia Rating [CDR] 2.4 + 1.7). Densities of neuritic plaques (NPs) and of neurofibrillary tangles (NFTs) were assessed in several neocortical regions and in the hippocampus, entorhinal cortex, and amygdala. Diabetic subjects were classified according to their recorded lifetime antidiabetic medications: none (n = 29), insulin only (n = 49), diabetes medications other than insulin only (n = 28), or concomitant use of both insulin and any oral antidiabetic medications (n = 18). For each dependent variable, analysis of covariance controlling for age at death, sex, and CDR distinguished among the nondiabetic patients and four diabetic subgroups. Results: There were differences among the five groups for NP ratings in the entorhinal cortex ( p = 0.003), amygdala ( p = 0.009), and overall NP ( p = 0.014) as well as counts of NPs in all regions examined ( p values ranging from 0.009 to 0.04). NP ratings in the hippocampus ( p = 0.057) and the combined neocortical measure ( p = 0.052) approached significance. In each analysis, the concomitant medication group had significantly fewer NPs (∼20%) than any of the other groups, which were relatively similar. No significant NFT differences were found. Conclusion: The results of this study suggest that the combination of insulin with other diabetes medication is associated with substantially lower neuritic plaque density consistent with the effects of both on the neurobiology of insulin.

Published
2008

41. A phenotype for genetic studies of successful cognitive aging

Author

Jeremy M. Silverman, Hillel Grossman, Michal Schnaider-Beeri, Joy Wang, James Schmeidler, and Rachel Lally

Subjects
Male, Proband, Aging, Pediatrics, medicine.medical_specialty, Lower risk, Cellular and Molecular Neuroscience, Cognition, Alzheimer Disease, Risk Factors, Epidemiology, medicine, Humans, Dementia, Genetic Predisposition to Disease, Family history, Genetics (clinical), Aged, Aged, 80 and over, Successful aging, business.industry, Middle Aged, medicine.disease, Psychiatry and Mental health, Phenotype, Genetic epidemiology, Female, Alzheimer's disease, business
Abstract

Survival from Alzheimer's disease (AD) and other dementias into late old age may be a useful phenotype for genetic studies of successful cognitive aging. To support molecular genetics studies for successful cognitive aging, we conducted a two-stage study to determine an optimal age phenotype for successful cognitive aging. First, risk of AD was evaluated, through informant interviews, in 4,794 parents and siblings of 976 elderly nondemented probands who were divided into three different proband age groups: those aged 60-74, 75-89, and 90+. Relatives of probands aged 90+ had a significantly lower risk than the relatives of the other two proband groups. Second, this sample was combined with an earlier sample (combined nondemented elderly probands: n = 2,025; relatives: n = 10,506), and a series of proband age groups (i.e., 75-79, 80-84, 85-89, 90+) were used to determine which optimally identifies a group of relatives with low AD risk. Using the relatives of the nondemented proband aged 60-74 as the reference group, there were reductions in cumulative risk among relatives of probands aged 85-89 and 90+, but only the latter group also showed significant reductions to the relatives of probands aged 75-79, 80-84, and 85-89. This pattern of results varied little by sex. Finally, cumulative AD risk curves were similar between relatives of probands aged 90-94 and 95+. These results suggest that age 90 is an optimal age threshold to use for both men and women in genetic studies seeking to identify genes associated with successful cognitive aging.

Published
2008

42. Increased longevity in offspring of mothers with alzheimer's disease

Author

Hillel Grossman, James Schmeidler, Rachel Lally, Rebecca K. West, Michal Schnaider-Beeri, Xiaodong Luo, Joy Wang, and Jeremy M. Silverman

Subjects
Male, Offspring, media_common.quotation_subject, Longevity, Disease, Neuropathology, Article, Cellular and Molecular Neuroscience, Alzheimer Disease, Humans, Medicine, Genetics (clinical), Aged, media_common, Aged, 80 and over, Sex Characteristics, business.industry, Proportional hazards model, Age Factors, Family aggregation, medicine.disease, Survival Analysis, Psychiatry and Mental health, Life expectancy, Adult Children, Female, Alzheimer's disease, business, Demography
Abstract

Life expectancy is a familial trait. However, the effectiveness of using the age at death of a deceased parent to estimate life expectancy in their offspring can vary depending on whether death in the parent was due to extrinsic versus intrinsic causes, as well as demographic characteristics such as sex. While Alzheimer’s disease (AD) risk increases with increased age, mortality for individuals with AD is increased in contrast to comparably aged individuals without AD. Yet in most cases it is not the defining neuropathology of AD that directly terminates life but instead conditions and illnesses extrinsic to AD pathology that nevertheless have increased likelihood in its presence. For this reason, we hypothesized that offspring of AD mothers would have greater longevity than offspring of mothers without AD (insufficient numbers prevented a comparable analysis using fathers with AD). The longevity of 345 offspring of 100 deceased 60+ year old AD mothers was compared with 5,465 offspring in 1,312 deceased 60+ year old non-AD mothers. We used a proportional hazards model that accounted for clustered (nonindependent) observations due to the inclusion of several offspring from the same family. In both an unadjusted model and one that adjusted for the age at death in the mother, and the sex and birth year in the offspring we found evidence for increased longevity in the offspring of AD mothers. The results suggest that, in addition to genes that might directly affect pathways leading to AD, there may be familial/genetic factors not connected to specific pathophysiological processes in AD but instead associated with increased longevity that contribute to the familial aggregation observed in AD.

Published
2007

43. P3‐122: The challenges of recruiting individuals with mild cognitive impairment (MCI) for biomarker studies in a veteran population

Author

Hillel Grossman, Mary Sano, Dongming Cai, Xiaodong Luo, Christopher Van Hise, Sam Gandy, Lara Akinleye, and Gregory A. Elder

Subjects
Gerontology, education.field_of_study, Epidemiology, Health Policy, Population, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, Biomarker (medicine), Neurology (clinical), Geriatrics and Gerontology, Mild cognitive impairment (MCI), Psychology, education, Clinical psychology
Published
2015

44. Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis

Author

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

Subjects
0301 basic medicine, Male, Aging, General Physics and Astronomy, Disease, Neurodegenerative, Alzheimer's Disease, Brain mapping, Diagnostic Radiology, Computer-Assisted, 0302 clinical medicine, Models, 2.1 Biological and endogenous factors, Alzheimer's Disease including Alzheimer's Disease Related Dementias, Aetiology, Cognitive decline, Brain Mapping, Multidisciplinary, Brain, Cognition, Blood Proteins, Statistical, Middle Aged, Magnetic Resonance Imaging, Cerebrovascular Circulation, Neurological, Disease Progression, Biomedical Imaging, Female, Alzheimer's disease, Alzheimer's Disease Neuroimaging Initiative, Science, Neuroimaging, tau Proteins, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Alzheimer Disease, Image Interpretation, Computer-Assisted, Acquired Cognitive Impairment, medicine, Humans, Cognitive Dysfunction, Image Interpretation, Pathological, Aged, Amyloid beta-Peptides, Models, Statistical, business.industry, Prevention, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer’s Disease Neuroimaging Initiative, General Chemistry, medicine.disease, Brain Disorders, 030104 developmental biology, Glucose, Positron-Emission Tomography, Multivariate Analysis, Dementia, business, Neuroscience, 030217 neurology & neurosurgery, Biomarkers
Abstract

Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD–abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions., Late-onset Alzheimer's disease (LOAD) is a complex multi-factorial disorder. Here, the authors perform a data-driven analysis of LOAD progression, including multimodal brain imaging, plasma and CSF biomarkers, and find vascular dysfunction is among the earliest and strongest altered events.

Published
2015

45. Coronary artery disease is associated with Alzheimer disease neuropathology in APOE4 carriers

Author

Abdul Majeed Siddiqui, Daniel P. Perl, Michael A. Rapp, Gerson T. Lesser, Clive Rosendorff, Dushyant P. Purohit, Michal Schnaider Beeri, John T. Fallon, James Schmeidler, Vahram Haroutunian, Hillel Grossman, and Jeremy M. Silverman

Subjects
Male, medicine.medical_specialty, Pathology, Genotype, Heart Ventricles, Apolipoprotein E4, Aortic Diseases, Cardiomegaly, Coronary Disease, Plaque, Amyloid, Late onset, Autopsy, Comorbidity, Neuropathology, Severity of Illness Index, Article, Coronary artery disease, Apolipoproteins E, Degenerative disease, Alzheimer Disease, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Alleles, Coronary atherosclerosis, Aged, 80 and over, business.industry, Brain, Neurofibrillary Tangles, Organ Size, Atherosclerosis, medicine.disease, Cardiology, Female, Neurology (clinical), Alzheimer's disease, business
Abstract

To examine the associations between postmortem Alzheimer disease (AD) neuropathology and autopsy-verified cardiovascular disease.The authors examined 99 subjects (mean age at death = 87.6; SD = 8.7) from the Mount Sinai School of Medicine Department of Psychiatry Brain Bank who were devoid of cerebrovascular disease-associated lesions or of non-AD-related neuropathology. Density of neuritic plaques (NPs) and neurofibrillary tangles (NFTs) as well as coronary artery and aortic atherosclerosis, left ventricular wall thickness, and heart weight were measured. Partial correlations were used to assess the associations of the four cardiovascular variables with NPs and NFTs in the hippocampus, entorhinal cortex, and multiple regions of the cerebral cortex after controlling for age at death, sex, dementia severity, body mass index, and ApoE genotype. These analyses were also repeated separately for ApoE4 carriers and noncarriers.The extent of coronary artery disease and to a lesser extent atherosclerosis were significantly associated with the density of cardinal neuropathologic lesions of AD in this autopsy sample (significant correlations between 0.22 and 0.29). These associations were more pronounced for the ApoE4 allele carriers (n = 42; significant correlations between 0.34 and 0.47).The degree of coronary artery disease is independently associated with the cardinal neuropathological lesions of Alzheimer disease. These associations are primarily attributable to individuals with the ApoE4 allele.

Published
2006

46. Emerging Therapeutics for Alzheimer's Disease: An Avenue of Hope

Author

Steven C. Samuels and Hillel Grossman

Subjects
N-Methylaspartate, Amyloid, Disease, Bioinformatics, Antioxidants, Pharmacotherapy, Alzheimer Disease, Neurotrophic factors, Humans, Medicine, Nootropic Agents, Chelating Agents, Clinical Trials as Topic, Vaccines, business.industry, Brain, Cardiovascular Agents, medicine.disease, Clinical trial, Psychiatry and Mental health, Cardiovascular agent, Drug Therapy, Combination, Cholinesterase Inhibitors, Neurology (clinical), Alzheimer's disease, business
Abstract

Emerging therapies for Alzheimer's disease offer hope to patients and their caregivers. Future treatments will probably include combination approaches with agents that modify amyloid processing, deposition, and clearance. One example, the AD vaccine, reduced amyloid burden and changed behavior in animal models of AD, but the human trial was halted when several subjects developed brain inflammation. Anti-inflammatory agents have epidemiologic support, but clinical trials have been disappointing, possibly related to inadequate study with anti-inflammatory agents that modify amyloid processing. Agents that target known cardiovascular risk factors, such as hypercholesterolemia, hypertension, and insulin resistance, have epidemiologic, preclinical, and clinical evidence to warrant further investigation. Heavymetal chelators, antioxidants, neurotrophic factors, glutaminergic modulators, and agents that modify hyper-phosphorylation of Tau are other approaches in research and development.

Published
2003

47. NORMAL HOMOCYSTEINE LEVELS IN WELL-FUNCTIONING OLDEST-OLD INDIVIDUALS DESPITE LOW KIDNEY FUNCTION

Author

Erik Langhoff, Hillel Grossman, Clive Rosendorff, Joy Wang, Jaime Uribarri, Michal Schnaider Beeri, James Schmeidler, Jeremy M. Silverman, and Rachel Lally

Subjects
medicine.medical_specialty, Creatinine, Homocysteine, business.industry, Confounding, Renal function, chemistry.chemical_compound, Endocrinology, chemistry, Internal medicine, Cohort, medicine, Vitamin B12, Geriatrics and Gerontology, Risk factor, business, Body mass index
Abstract

To the Editor: Homocysteine is a sulfur-containing metabolite of methionine that is emerging as an independent risk factor for atherosclerosis,1 arterial and venous thrombosis,2 and mortality.3 Previous studies, focusing on relatively young older people, have shown that homocysteine is higher in men and increases with age, smoking, lower vitamin B12, folate, and renal function levels.4 Recently, we studied the relationships between homocysteine levels and the clinical and laboratory measures that have been typically associated with them in younger cohorts, using a sample of 117 well-functioning, cognitively intact community-dwelling oldest-old (aged ≥ 85). The relationship between change in homocysteine over time and these same factors was also examined in the subsample for whom follow-up data were available. Nonfasting plasma homocysteine levels were measured according to a method previously described with minor modifications.5 Vitamin B12, serum folate, serum creatinine, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and albumin were collected using standard techniques. Glomerular filtration rate (GFR), was estimated using the Cockroft-Gault formula.6 Age, education, body mass index, and smoking information were also collected. Data on homocysteine, vitamin B12, folate, and creatinine levels were transformed using natural logarithms, to make the distributions approximately normal for statistical analysis purposes. The means and standard deviations were 12.4 ± 3.4 µmol/L for homocysteine, 1.0 ± 0.35 mg/dL for creatinine, and 45.1 ± 12.7 mL/min for GFR. Mean age was 89.2 ± 2.8; 70.5% were female. Approximately one-third of the sample had homocysteinemia (≥ 13 µmol/L7). GFR was impaired ( 1.4 mg/dL in 29.7% of men and >1.1 mg/dL in 22.4% of women). None of the subjects had low folate levels, and only 1.7% had low vitamin B12 levels (

Published
2006

48. Early-onset substance abuse and community violence by outpatients with chronic mental illness

Author

Robin Ruthazer, Hillel Grossman, Carl E. Fulwiler, and Catherine Forbes

Subjects
Adult, Male, Risk, medicine.medical_specialty, Adolescent, Substance-Related Disorders, Assertive community treatment, Poison control, Alcohol abuse, Comorbidity, Violence, Suicide prevention, Activities of Daily Living, Outpatients, Injury prevention, Ambulatory Care, Humans, Medicine, Child, Psychiatry, business.industry, Mental Disorders, Middle Aged, medicine.disease, Mental illness, Causality, Substance abuse, Alcoholism, Psychiatry and Mental health, Massachusetts, Chronic Disease, Female, business, Clinical psychology
Abstract

OBJECTIVE: This study examined the relationship between violence and substance abuse among patients with chronic mental illness living in the community. METHODS: All referrals over a one-year period to an urban assertive community treatment team were evaluated systematically with a standardized intake protocol. Thirty-seven patients with a history of violence in the community were compared with 27 patients without such a history on a variety of clinical and demographic variables. RESULTS: More than half of the patients (58 percent) had a history of violence in the community. The only significant differences between those with a history of violence and those without involved alcohol or drug use. The single best predictor of violence was the onset of alcohol or drug abuse in late childhood or early adolescence. CONCLUSIONS: In this sample, very early onset of substance abuse among people who developed mental illness was associated with the greatest risk of community violence. Thus at least some of the causal determinants of violence in this sample may precede the onset of adult mental illness. Language: en

Published
1997

49. Cognitive Performance and Regional Brain Volume in Human Immunodeficiency Virus Type 1 Infection

Author

Charlyne Hickey, Christopher Cox, Andrew Feigin, Robert G. Holloway, Hillel Grossman, Eric D. Caine, Leena Ketonen, Heather Booth, and Karl Kieburtz

Subjects
Adult, Male, medicine.medical_specialty, Pathology, medicine.medical_treatment, HIV Infections, Neuropsychological Tests, Hippocampus, Central nervous system disease, Cognition, Atrophy, Arts and Humanities (miscellaneous), Acquired immunodeficiency syndrome (AIDS), Internal medicine, medicine, Humans, Dementia, Effects of sleep deprivation on cognitive performance, medicine.diagnostic_test, business.industry, Brain, Immunosuppression, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Brain size, HIV-1, Female, Neurology (clinical), Caudate Nucleus, business
Abstract

Background: Brain atrophy has been reported to occur in advancing human immunodeficiency virus (HIV) infection, particularly in patients with HIV-related dementia. Atrophy of the caudate region, as assessed by magnetic resonance imaging measures, has been reported to correlate with cognitive impairment in patients with HIV infection; however, differences in the severity of HIV-induced immunosuppression may have contributed to these findings. Objective: To determine the relationship between regional brain volumes and cognitive performance in individuals with HIV infection. Patients and Methods: We evaluated 11 patients with advanced HIV disease by using neuropsychologic tests and quantitative magnetic resonance imaging volume analysis. Setting: University hospital, involving patients from a clinical trial. Results: Caudate volume, expressed as a ratio of total intracranial volume, correlated with performance on the Trails A and Grooved Pegboard tests, but not with other tests of memory, motor speed, or mood (adjusted for age and education). Hippocampal volume did not correlate with any of the neuropsychologic tests. Conclusions: Caudate volume in patients with advanced HIV disease is associated with poor performance on neuropsychologic tests of complex motor and sequencing skills. Hippocampal volume does not appear to be related to impairment on neuropsychologic tests. These findings are independent of the degree of immunosuppression and the overall extent of brain atrophy; however, these results must be interpreted with some caution, given the limited sample size.

Published
1996

50. C-reactive protein and familial risk for dementia: a phenotype for successful cognitive aging

Author

Mary Sano, Irina N. Bespalova, Michal Schnaider Beeri, James Schmeidler, Clive Rosendorff, Vahram Haroutunian, José R. Carrión-Baralt, Rebecca K. West, Hillel Grossman, and Jeremy M. Silverman

Subjects
Gerontology, Proband, Male, Risk, medicine.medical_specialty, Aging, Health Status, Lower risk, Cognition, Internal medicine, Surveys and Questionnaires, medicine, Dementia, Humans, Family, Genetic Predisposition to Disease, Family history, Aged, Aged, 80 and over, biology, Proportional hazards model, Hazard ratio, C-reactive protein, Age Factors, Articles, medicine.disease, C-Reactive Protein, Phenotype, biology.protein, Neurology (clinical), Psychology
Abstract

Identifying phenotypes for successful cognitive aging, intact cognition into late-old age (age 75), can help identify genes and neurobiological systems that may lead to interventions against and prevention of late-life cognitive impairment. The association of C-reactive protein (CRP) with cognitive impairment and dementia, observed primarily in young-elderly samples, appears diminished or reversed in late-old age (75+ years). A family history study determined if high CRP levels in late-old aged cognitively intact probands are associated with a reduced risk of dementia in their first-degree family members, suggesting a familial successful cognitive aging phenotype.The primary sample was 1,329 parents and siblings of 277 cognitively intact male veteran probands at least 75 years old. The replication sample was 202 relatives of 51 cognitively intact community-ascertained probands at least 85 years old. Relatives were assessed for dementia by proband informant interview. Their hazard ratio (HR) for dementia as a function of the proband's log-transformed CRP was calculated using the proportional hazards model.Covarying for key demographics, higher CRP in probands was strongly associated with lower risk of dementia in relatives (HR = 0.55 [95% confidence interval (CI) 0.41, 0.74], p0.02). The replication sample relationship was in the same direction, stronger in magnitude, and also significant (HR = 0.15 [95% CI 0.06, 0.37], p0.0001).Relatives of successful cognitive aging individuals with high levels of CRP are relatively likely to remain free of dementia. High CRP in successful cognitive aging individuals may constitute a phenotype for familial-and thus possibly genetic-successful cognitive aging.

Published
2012

Catalog

Books, media, physical & digital resources
See catalog results