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1. The genetic architecture of Alzheimer disease risk in the Ohio and Indiana Amish

Author: Michael D. Osterman, Yeunjoo E. Song, Larry D. Adams, Renee A. Laux, Laura J. Caywood, Michael B. Prough, Jason E. Clouse, Sharlene D. Herington, Susan H. Slifer, Audrey Lynn, M. Denise Fuzzell, Sarada L. Fuzzell, Sherri D. Hochstetler, Kristy Miskimen, Leighanne R. Main, Daniel A. Dorfsman, Paula Ogrocki, Alan J. Lerner, Jairo Ramos, Jeffery M. Vance, Michael L. Cuccaro, William K. Scott, Margaret A. Pericak-Vance, and Jonathan L. Haines
Subjects: Alzheimer disease, polygenic risk score, PRS, genetic risk score, GRS, Amish, Genetics, QH426-470
Abstract: Summary: Alzheimer disease (AD) is the most common type of dementia and is currently estimated to affect 6.2 million Americans. It ranks as the sixth leading cause of death in the United States, and the proportion of deaths due to AD has been increasing since 2000, while the proportion of many other leading causes of deaths have decreased or remained constant. The risk for AD is multifactorial, including genetic and environmental risk factors. Although APOE ε4 remains the largest genetic risk factor for AD, more than 26 other loci have been associated with AD risk. Here, we recruited Amish adults from Ohio and Indiana to investigate AD risk and protective genetic effects. As a founder population that typically practices endogamy, variants that are rare in the general population may be of a higher frequency in the Amish population. Since the Amish have a slightly lower incidence and later age of onset of disease, they represent an excellent and unique population for research on protective genetic variants. We compared AD risk in the Amish and to a non-Amish population through APOE genotype, a non-APOE genetic risk score of genome-wide significant variants, and a non-APOE polygenic risk score considering all of the variants. Our results highlight the lesser relative impact of APOE and differing genetic architecture of AD risk in the Amish compared to a non-Amish, general European ancestry population.
Published: 2022
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2. 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
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3. Prediction and Classification of Alzheimer’s Disease Based on Combined Features From Apolipoprotein-E Genotype, Cerebrospinal Fluid, MR, and FDG-PET Imaging Biomarkers

Author: Yubraj Gupta, Ramesh Kumar Lama, Goo-Rak Kwon, Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, Steven Chao, Scott Mackin, Rema Raman, Erin Drake, Mike Donohue, Gustavo Jimenez, Kelly Harless, Jennifer Salazar, Yuliana Cabrera, Lindsey Hergesheimer, Elizabeth Shaffer, Craig Nelson, David Bickford, Meryl Butters, Michelle Zmuda, Denise Reyes, Kelley M. Faber, Kelly N. Nudelman, Yiu Ho Au, Kelly Scherer, Daniel Catalinotto, Samuel Stark, Elise Ong, and Dariella Fernandez
Subjects: Alzheimer's disease, MCIs (MCI stable), MCIc (MCI converted), sMRI, FDG-PET, CSF, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Alzheimer's disease (AD), including its mild cognitive impairment (MCI) phase that may or may not progress into the AD, is the most ordinary form of dementia. It is extremely important to correctly identify patients during the MCI stage because this is the phase where AD may or may not develop. Thus, it is crucial to predict outcomes during this phase. Thus far, many researchers have worked on only using a single modality of a biomarker for the diagnosis of AD or MCI. Although recent studies show that a combination of one or more different biomarkers may provide complementary information for the diagnosis, it also increases the classification accuracy distinguishing between different groups. In this paper, we propose a novel machine learning-based framework to discriminate subjects with AD or MCI utilizing a combination of four different biomarkers: fluorodeoxyglucose positron emission tomography (FDG-PET), structural magnetic resonance imaging (sMRI), cerebrospinal fluid (CSF) protein levels, and Apolipoprotein-E (APOE) genotype. The Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline dataset was used in this study. In total, there were 158 subjects for whom all four modalities of biomarker were available. Of the 158 subjects, 38 subjects were in the AD group, 82 subjects were in MCI groups (including 46 in MCIc [MCI converted; conversion to AD within 24 months of time period], and 36 in MCIs [MCI stable; no conversion to AD within 24 months of time period]), and the remaining 38 subjects were in the healthy control (HC) group. For each image, we extracted 246 regions of interest (as features) using the Brainnetome template image and NiftyReg toolbox, and later we combined these features with three CSF and two APOE genotype features obtained from the ADNI website for each subject using early fusion technique. Here, a different kernel-based multiclass support vector machine (SVM) classifier with a grid-search method was applied. Before passing the obtained features to the classifier, we have used truncated singular value decomposition (Truncated SVD) dimensionality reduction technique to reduce high dimensional features into a lower-dimensional feature. As a result, our combined method achieved an area under the receiver operating characteristic (AU-ROC) curve of 98.33, 93.59, 96.83, 94.64, 96.43, and 95.24% for AD vs. HC, MCIs vs. MCIc, AD vs. MCIs, AD vs. MCIc, HC vs. MCIc, and HC vs. MCIs subjects which are high relative to single modality results and other state-of-the-art approaches. Moreover, combined multimodal methods have improved the classification performance over the unimodal classification.
Published: 2019
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4. The Influence of Cerebrospinal Fluid Abnormalities and APOE 4 on PHF-Tau Protein: Evidence From Voxel Analysis and Graph Theory

Author: Yuan Li, Zhijun Yao, Yue Yu, Yu Fu, Ying Zou, Bin Hu, for the Alzheimer’s Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Tom Montine, Gustavo Jimenez, Michael Donohue, Devon Gessert, Kelly Harless, Jennifer Salazar, Yuliana Cabrera, Sarah Walter, Lindsey Hergesheimer, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Joseph Quinn, Lisa C. Silbert, Betty Lind, Jeffrey A. Kaye, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Jaimie Ziolkowski, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Javier Villanueva-Meyer, Valory Pavlik, Nathaniel Pacini, Ashley Lamb, Joseph S. Kass, Rachelle S. Doody, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Randy Yeh, Beau Ances, David Winkfield, Maria Carroll, Angela Oliver, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Hillel Grossman, Effie Mitsis, Raj C. Shah, Melissa Lamar, Patricia Samuels, Ranjan Duara, Maria T. Greig-Custo, Rosemarie Rodriguez, Chiadi Onyike, Daniel D’Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Jamika Singleton-Garvin, Anaztasia Ulysse, Mrunalini Gaikwad, P. Murali Doraiswamy, Jeffrey R. Petrella, Olga James, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Jason H. Karlawish, David A. Wolk, Sanjeev Vaishnavi, Christopher M. Clark, Steven E. Arnold, Charles D. Smith, Greg Jicha, Peter Hardy, Riham El Khouli, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Kim Martin, Nancy Kowalksi, Melanie Keltz, Bonnie S. Goldstein, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Gaby Thai, Aimee Pierce, Beatriz Yanez, Elizabeth Sosa, Megan Witbracht, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Ellen Woo, Daniel H.S. Silverman, Edmond Teng, Sarah Kremen, Liana Apostolova, Kathleen Tingus, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Chris (Chinthaka) Heyn, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, William Pavlosky, Irina Rachinsky, Dick Drost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad A. Marshall, Jerome Yesavage, Joy L. Taylor, Steven Chao, Barton Lane, Allyson Rosen, Jared Tinklenberg, Edward Zamrini, Christine M. Belden, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Ntekim E. Oyonumo, Joanne Allard, Olu Ogunlana, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Joel Hetelle, Kathryn DeMarco, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Rawan Tarawneh, Earl A. Zimmerman, Dzintra Celmins, David Hart, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Mia Yang, Akiva Mintz, Rhode Island, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Courtney Bodge, Stephen Salloway, Paul Malloy, Stephen Correia, Athena Lee, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, John Rogers, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Delwyn D. Miller, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Susan K. Schultz, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Christi Leach, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Lindsey Hergesheimen, Jacqueline Hayes, Shannon Finley, Susan Landau, Erin Householder, Karl Friedl, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Bonnie Goldstein, Kimberly S. Martin, Steven G. Potkin, Adrian Preda, Dana Nguyen, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Gad Marshall, Marwan N. Sabbagh, Sandra A. Jacobson, Saba Wolday, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, Scott Mackin, Rema Raman, Erin Drake, Mike Donohue, Elizabeth Shaffer, Craig Nelson, David Bickford, Meryl Butters, Michelle Zmuda, Denise Reyes, Kelley M. Faber, Kelly N. Nudelman, Yiu Ho Au, Kelly Scherer, Daniel Catalinotto, Samuel Stark, Elise Ong, and Dariella Fernandez
Subjects: PHF-Tau, graph theory, network properties, APOE 4, CSF-Tau, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Mild cognitive impairment (MCI) is a transitional state between the cognitive changes in normal aging and Alzheimer’s disease (AD), which induces abnormalities in specific brain regions. Previous studies showed that paired helical filaments Tau (PHF-Tau) protein is a potential pathogenic protein which may cause abnormal brain function and structure in MCI and AD patients. However, the understanding of the PHF-Tau protein network in MCI patients is limited. In this study, 225 subjects with PHF-Tau Positron Emission Tomography (PET) images were divided into four groups based on whether they carried Apolipoprotein E ε4 (APOE 4) or abnormal cerebrospinal fluid Total-Tau (CSF T-Tau). They are two important pathogenic factors that might cause cognitive function impairment. The four groups were: individuals harboring CSF T-Tau pathology but no APOE 4 (APOE 4−T+); APOE 4 carriers with normal CSF T-Tau (APOE 4+T−); APOE 4 carriers with abnormal CSF T-Tau (APOE 4+T+); and APOE 4 noncarriers with abnormal CSF T-Tau (APOE 4−T−). We explored the topological organization of PHF-Tau networks in these four groups and calculated five kinds of network properties: clustering coefficient, shortest path length, Q value of modularity, nodal centrality and degree. Our findings showed that compared with APOE 4−T− group, the other three groups showed different alterations in the clustering coefficient, shortest path length, Q value of modularity, nodal centrality and degree. Simultaneously, voxel-level analysis was conducted and the results showed that compared with APOE 4−T− group, the other three groups were found increased PHF-Tau distribution in some brain regions. For APOE 4+T+ group, positive correlation was found between the value of PHF-Tau distribution in altered regions and Functional Assessment Questionnaire (FAQ) score. Our results indicated that the effects of APOE 4 and abnormal CSF T-Tau may induce abnormalities of PHF-Tau protein and APOE 4 has a greater impact on PHF-Tau than abnormal CSF T-Tau. Our results may be particularly helpful in uncovering the pathophysiology underlying the cognitive dysfunction in MCI patients.
Published: 2019
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5. New Perspective for Non-invasive Brain Stimulation Site Selection in Mild Cognitive Impairment: Based on Meta- and Functional Connectivity Analyses

Author: Jiao Liu, Binlong Zhang, Georgia Wilson, Jian Kong, the Alzheimer’s Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, and Steven Chao
Subjects: mild cognitive impairment, non-invasive brain stimulation, stimulation site, meta-analysis, resting state functional connectivity, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: BackgroundNon-invasive brain stimulation (NIBS) has been widely used to treat mild cognitive impairment (MCI). However, there exists no consensus on the best stimulation sites.ObjectiveTo explore potential stimulation locations for NIBS treatment in patients with MCI, combining meta- and resting state functional connectivity (rsFC) analyses.MethodsThe meta-analysis was conducted to identify brain regions associated with MCI. Regions of interest (ROIs) were extracted based on this meta-analysis. The rsFC analysis was applied to 45 MCI patients to determine brain surface regions that are functionally connected with the above ROIs.ResultsWe found that the dorsolateral prefrontal cortex (DLPFC) and inferior frontal gyrus (IFG) were the overlapping brain regions between our results and those of previous studies. In addition, we recommend that the temporoparietal junction (including the angular gyrus), which was found in both the meta- and rsFC analysis, should be considered in NIBS treatment of MCI. Furthermore, the bilateral orbital prefrontal gyrus, inferior temporal gyrus, medial superior frontal gyrus, and right inferior occipital gyrus may be potential brain stimulation sites for NIBS treatment of MCI.ConclusionOur results provide several potential sites for NIBS, such as the DLFPC and IFG, and may shed light on the locations of NIBS sites in the treatment of patients with MCI.
Published: 2019
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6. Performing Sparse Regularization and Dimension Reduction Simultaneously in Multimodal Data Fusion

Author: Zhengshi Yang, Xiaowei Zhuang, Christopher Bird, Karthik Sreenivasan, Virendra Mishra, Sarah Banks, Dietmar Cordes, the Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, Steven Chao, Scott Mackin, Rema Raman, Erin Drake, Mike Donohue, Gustavo Jimenez, Kelly Harless, Jennifer Salazar, Yuliana Cabrera, Lindsey Hergesheimer, Elizabeth Shaffer, Craig Nelson, David Bickford, Meryl Butters, Michelle Zmuda, Denise Reyes, Kelley M. Faber, Kelly N. Nudelman, Yiu Ho Au, Kelly Scherer, Daniel Catalinotto, Samuel Stark, Elise Ong, and Dariella Fernandez
Subjects: sparse principal component analysis, PCA, canonical correlation analysis, CCA, data fusion, mild cognitive impairment, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Collecting multiple modalities of neuroimaging data on the same subject is increasingly becoming the norm in clinical practice and research. Fusing multiple modalities to find related patterns is a challenge in neuroimaging analysis. Canonical correlation analysis (CCA) is commonly used as a symmetric data fusion technique to find related patterns among multiple modalities. In CCA-based data fusion, principal component analysis (PCA) is frequently applied as a preprocessing step to reduce data dimension followed by CCA on dimension-reduced data. PCA, however, does not differentiate between informative voxels from non-informative voxels in the dimension reduction step. Sparse PCA (sPCA) extends traditional PCA by adding sparse regularization that assigns zero weights to non-informative voxels. In this study, sPCA is incorporated into CCA-based fusion analysis and applied on neuroimaging data. A cross-validation method is developed and validated to optimize the parameters in sPCA. Different simulations are carried out to evaluate the improvement by introducing sparsity constraint to PCA. Four fusion methods including sPCA+CCA, PCA+CCA, parallel ICA and sparse CCA were applied on structural and functional magnetic resonance imaging data of mild cognitive impairment subjects and normal controls. Our results indicate that sPCA significantly can reduce the impact of non-informative voxels and lead to improved statistical power in uncovering disease-related patterns by a fusion analysis.
Published: 2019
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7. Quantitative 18F-AV1451 Brain Tau PET Imaging in Cognitively Normal Older Adults, Mild Cognitive Impairment, and Alzheimer's Disease Patients

Author: Qian Zhao, Min Liu, Lingxia Ha, Yun Zhou, Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, Steven Chao, Scott Mackin, Rema Raman, Erin Drake, Mike Donohue, Gustavo Jimenez, Kelly Harless, Jennifer Salazar, Yuliana Cabrera, Lindsey Hergesheimer, Elizabeth Shaffer, Craig Nelson, David Bickford, Meryl Butters, Michelle Zmuda, Denise Reyes, Kelley M. Faber, Kelly N. Nudelman, Yiu Ho Au, Kelly Scherer, Daniel Catalinotto, Samuel Stark, Elise Ong, and Dariella Fernandez
Subjects: 18F-AV1451, Tau PET, cognitively normal, mild cognition impairment, Alzheimer's disease, Neurology. Diseases of the nervous system, RC346-429
Abstract: Recent developments of tau Positron Emission Tomography (PET) allows assessment of regional neurofibrillary tangles (NFTs) deposition in human brain. Among the tau PET molecular probes, 18F-AV1451 is characterized by high selectivity for pathologic tau aggregates over amyloid plaques, limited non-specific binding in white and gray matter, and confined off-target binding. The objectives of the study are (1) to quantitatively characterize regional brain tau deposition measured by 18F-AV1451 PET in cognitively normal older adults (CN), mild cognitive impairment (MCI), and AD participants; (2) to evaluate the correlations between cerebrospinal fluid (CSF) biomarkers or Mini-Mental State Examination (MMSE) and 18F-AV1451 PET standardized uptake value ratio (SUVR); and (3) to evaluate the partial volume effects on 18F-AV1451 brain uptake.Methods: The study included total 115 participants (CN = 49, MCI = 58, and AD = 8) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed 18F-AV1451 PET images, structural MRIs, and demographic and clinical assessments were downloaded from the ADNI database. A reblurred Van Cittertiteration method was used for voxelwise partial volume correction (PVC) on PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. The parametric images of 18F-AV1451 SUVR relative to cerebellum were calculated. The ROI SUVR measurements from PVC and non-PVC SUVR images were compared. The correlation between ROI 18F-AV1451 SUVR and the measurements of MMSE, CSF total tau (t-tau), and phosphorylated tau (p-tau) were also assessed.Results:18F-AV1451 prominently specific binding was found in the amygdala, entorhinal cortex, parahippocampus, fusiform, posterior cingulate, temporal, parietal, and frontal brain regions. Most regional SUVRs showed significantly higher uptake of 18F-AV1451 in AD than MCI and CN participants. SUVRs of small regions like amygdala, entorhinal cortex and parahippocampus were statistically improved by PVC in all groups (p < 0.01). Although there was an increasing tendency of 18F-AV-1451 SUVRs in MCI group compared with CN group, no significant difference of 18F-AV1451 deposition was found between CN and MCI brains with or without PVC (p > 0.05). Declined MMSE score was observed with increasing 18F-AV1451 binding in amygdala, entorhinal cortex, parahippocampus, and fusiform. CSF p-tau was positively correlated with 18F-AV1451 deposition. PVC improved the results of 18F-AV-1451 tau deposition and correlation studies in small brain regions.Conclusion: The typical deposition of 18F-AV1451 tau PET imaging in AD brain was found in amygdala, entorhinal cortex, fusiform and parahippocampus, and these regions were strongly associated with cognitive impairment and CSF biomarkers. Although more deposition was observed in MCI group, the 18F-AV-1451 PET imaging could not differentiate the MCI patients from CN population. More tau deposition related to decreased MMSE score and increased level of CSF p-tau, especially in ROIs of amygdala, entorhinal cortex and parahippocampus. PVC did improve the results of tau deposition and correlation studies in small brain regions and suggest to be routinely used in 18F-AV1451 tau PET quantification.
Published: 2019
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8. Corrigendum: Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images

Author: Shengwen Guo, Chunren Lai, Congling Wu, Guiyin Cen, The Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, and Steven Chao
Subjects: mild cognitive impairment, conversion, cortical feature, sparse-constrained regression, feature reduction, classification, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Published: 2017
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9. Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images

Author: Shengwen Guo, Chunren Lai, Congling Wu, Guiyin Cen, The Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, and Steven Chao
Subjects: mild cognitive impairment, conversion, cortical feature, sparse-constrained regression, feature reduction, classification, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI). Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions, and further differentiate MCI patients from normal states. Four cortical features, namely, gray matter volume, cortical thickness, surface area, and mean curvature, were explored for discriminative analysis among three groups including the stable MCI (sMCI), the converted MCI (cMCI), and the normal control (NC) groups. In this study, 158 subjects (72 NC, 46 sMCI, and 40 cMCI) were selected from the Alzheimer's Disease Neuroimaging Initiative. A sparse-constrained regression model based on the l2-1-norm was introduced to reduce the feature dimensionality and retrieve essential features for the discrimination of the three groups by using a support vector machine (SVM). An optimized strategy of feature addition based on the weight of each feature was adopted for the SVM classifier in order to achieve the best classification performance. The baseline cortical features combined with the longitudinal measurements for 2 years of follow-up data yielded prominent classification results. In particular, the cortical thickness produced a classification with 98.84% accuracy, 97.5% sensitivity, and 100% specificity for the sMCI–cMCI comparison; 92.37% accuracy, 84.78% sensitivity, and 97.22% specificity for the cMCI–NC comparison; and 93.75% accuracy, 92.5% sensitivity, and 94.44% specificity for the sMCI–NC comparison. The best performances obtained by the SVM classifier using the essential features were 5–40% more than those using all of the retained features. The feasibility of the cortical features for the recognition of anatomical patterns was certified; thus, the proposed method has the potential to improve the clinical diagnosis of sub-types of MCI and predict the risk of its conversion to Alzheimer's disease.
Published: 2017
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10. Early Neuropsychiatric Symptoms of Mild Cognitive Impairment Subtypes: An Analysis of the National Alzheimer’s Coordinating Center Database (P7-6.004)

Author: Joseph Malone, Mohamed Elkasaby, Brian Appleby, Charles Duffy, Lindsay Miller-Scott, Tamara Murphy, Paula Ogrocki, and Alan Lerner
Published: 2023

11. Psychometric approaches to defining cognitive phenotypes in the Old Order Amish

Author: Andrew Zaman, Laura Caywood, Michael Prough, Jason Clouse, Sharlene Harrington, Larry Adams, Denise Fuzzell, Sarada Fuzzell, Renee Laux, Sherri D. Hochstetler, Paula Ogrocki, Alan Lerner, Jeffery M. Vance, Jonathan L. Haines, William K. Scott, Margaret A. Pericak‐Vance, and Michael L. Cuccaro
Subjects: Psychiatry and Mental health, Geriatrics and Gerontology
Published: 2023

12. The genetic architecture of Alzheimer disease risk in the Ohio and Indiana Amish

Author: Sharlene D. Herington, Jonathan L. Haines, Sherri D Hochstetler, Jeffery M. Vance, Renee Laux, Yeunjoo E. Song, Jason E. Clouse, Michael D. Osterman, Leighanne R. Main, William K. Scott, Alan J. Lerner, Daniel A. Dorfsman, Sarada Fuzzell, Susan Slifer, Paula Ogrocki, Laura Caywood, Kristy Miskimen, Jairo Ramos, Audrey Lynn, Michael L. Cuccaro, Margaret A. Pericak-Vance, Michael Prough, Larry D. Adams, and M. Denise Fuzzell
Subjects: education.field_of_study, business.industry, Population, medicine.disease, Genetic architecture, Endogamy, Medicine, Dementia, Molecular Medicine, Age of onset, Alzheimer's disease, business, education, Genetics (clinical), Demography, Founder effect, Cause of death
Abstract: Alzheimer disease (AD) is the most common type of dementia and is currently estimated to affect 6.2 million Americans. It ranks as the sixth leading cause of death in the United States and the proportion of deaths due to AD has been increasing since the year 2000 while the proportion of many other leading causes of deaths have decreased or remained constant. The risk for AD is multifactorial, including genetic and environmental risk factors. Though APOE remains the largest genetic risk factor for AD, more than 26 other loci have been associated with AD risk. Here, we recruited from a population of Amish adults from Ohio and Indiana to investigate AD risk and protective genetic effects. With slightly lower incidence and later age of onset, it is thought that the Amish may hold protective genetic variants for AD. As a founder population that typically practices endogamy, variants that are rare in the general population may be at higher frequency in the Amish population. We characterized the genetic architecture of AD risk in the Amish and compared this to a non-Amish population, elucidating the lower relative importance of APOE and differing genetic architecture of the Amish compared to a general European ancestry population.
Published: 2021

13. Effect of Intensive Blood Pressure Control on Subtypes of Mild Cognitive Impairment and Risk of Progression from SPRINT study

Author: Michael Crowe, Virginia G. Wadley, Paula Ogrocki, Valerie M. Wilson, Sarah A. Gaussoin, Mark A. Supiano, Nicholas M. Pajewski, Clinton B. Wright, David M. Reboussin, Bonnie C. Sachs, Stephen R. Rapp, Lenore J. Launer, Alan J. Lerner, Gordon J. Chelune, Jennifer Martindale-Adams, Kaycee M Sink, Linda O. Nichols, Jeff D. Williamson, and Maryjo Cleveland
Subjects: medicine.medical_specialty, Blood Pressure, Neuropsychological Tests, Article, law.invention, Randomized controlled trial, law, Internal medicine, mental disorders, Medicine, Dementia, Humans, Cognitive Dysfunction, Survival analysis, Aged, Proportional Hazards Models, business.industry, Standard treatment, Hazard ratio, medicine.disease, Confidence interval, Clinical trial, Blood pressure, Hypertension, Disease Progression, Female, Geriatrics and Gerontology, business
Abstract: BACKGROUND: To examine the effect of intensive blood pressure control on the occurrence of subtypes of mild cognitive impairment (MCI) and determine the risk of progression to dementia or death. METHODS: Secondary analysis of a randomized trial of community-dwelling adults (≥50 years) with hypertension. Participants were randomized to a systolic blood pressure (SBP) goal of
Published: 2021

14. Genetic variants in the SHISA6 gene are associated with delayed cognitive impairment in two family datasets

Author: Jeffery M. Vance, Larry D. Adams, St.George-Hyslop Ph, Yq Song, Sharlene D. Herington, Laura Caywood, Michael L. Cuccaro, Fuzzell, Jairo Ramos, Zaman Af, Leighanne R. Main, Laframboise O, Sarada Fuzzell, Tatiana Foroud, Michael Prough, Patrice L. Whitehead, Haines Jl, Hochstetler Sd, Jason E. Clouse, Renee Laux, Osterman, Paula Ogrocki, Richard Mayeux, Susan Slifer, Margaret A. Pericak-Vance, Alan J. Lerner, William K. Scott, and Kristy Miskimen
Subjects: Chromosome 17 (human), Genetics, Minor allele frequency, Candidate gene, education.field_of_study, Population, Genotype, Locus (genetics), Genome-wide association study, Allele, Biology, education
Abstract: BackgroundStudies of cognitive impairment (CI) in Amish communities have identified sibships containing multiple CI and cognitively unimpaired (CU; unaffected after age 75) individuals. We hypothesize that these CU individuals may carry protective alleles delaying age at onset (AAO) of CI, preserving cognition in older age despite increased genetic risk. As well, the genetic and cultural isolation in the Amish since the early 1800s may have reduced the complexity of the genetic architecture of CI, increasing the power to detect protective alleles in this population. With this in mind we conducted a genome-wide study (GWAS) to identify loci associated with AAO of CI in a sample of Amish adults over age 75.Methods1,522 individuals aged 43-99 (mean age 73.1, 42% men) screened at least once for CI using the Modified Mini-Mental State exam (3MS) were genotyped using Illumina chipsets. Genotypes were imputed for 7,815,951 single nucleotide variants (SNV) with minor allele frequency (MAF) > 1%. The outcome studied was age, defined as 1) age at the first 3MS result indicating impairment (AAO; 3MS =87, 1,160 CU individuals). Cox mixed-effects models examined association between age and each SNV, adjusting for sex and familial relationships. To replicate genome-wide significant findings, SNVs in a 1 Megabase region centered on the peak SNV were examined for association with age using these same methods in the NIA-LOAD family study dataset (1,785 AD cases, 1,565 unaffected controls, mean age 73.5.ResultsThree SNV were significantly associated (pConclusionsThe replicated genome-wide significant association with AAO on chromosome 17 suggest this may be novel locus associated with delayed onset of AD. The associated SNP is located in the SHISA6 gene, which is involved in post-synaptic transmission in the hippocampus and is a biologically plausible candidate gene for AD.
Published: 2021

15. Lower Levels of Education Are Associated with Cognitive Impairment in the Old Order Amish

Author: William K. Scott, Alan J. Lerner, Paula Ogrocki, Sarada Fuzzell, Laura Caywood, Yeunjoo E. Song, Jeffery M. Vance, Patrice L. Whitehead, M. Denise Fuzzell, Jairo Ramos, Michael L. Cuccaro, Renee Laux, Kristy Miskimen, Larry D. Adams, Michael Prough, Margaret A. Pericak-Vance, Jonathan L. Haines, and Aneesa R. Chowdhury
Subjects: Male, Population, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, medicine, Dementia, Humans, Cognitive Dysfunction, 030212 general & internal medicine, Cognitive impairment, education, Socioeconomic status, Aged, Aged, 80 and over, education.field_of_study, General Neuroscience, Cognition, General Medicine, Middle Aged, medicine.disease, Educational attainment, Psychiatry and Mental health, Clinical Psychology, Logistic Models, Old Order Amish, Educational Status, Female, Geriatrics and Gerontology, Psychology, Amish, 030217 neurology & neurosurgery, Demography
Abstract: Background: Lower education has been reported to be associated with dementia. However, many studies have been done in settings where 12 years of formal education is the standard. Formal schooling in the Old Order Amish communities (OOA) ends at 8th grade which, along with their genetic homogeneity, makes it an interesting population to study the effect of education on cognitive impairment. Objective: The objective of this study was to examine the association of education with cognitive function in individuals from the OOA. We hypothesized that small differences in educational attainment at lower levels of formal education were associated with risk for cognitive impairment. Methods: Data of 2,426 individuals from the OOA aged 54–99 were analyzed. The Modified Mini-Mental State Examination (3MS-R) was used to classify participants as CI or normal. Individuals were classified into three education categories: 8 years of education. To measure the association of education with cognitive status, a logistic regression model was performed adding age and sex as covariates. Results: Our results showed that individuals who attained lowest levels of education (8 years (OR = 2.96 and 1.85). Conclusion: Even within a setting of low levels of formal education, small differences in educational attainment can still be associated with the risk of cognitive impairment. Given the homogeneity of the OOA, these results are less likely to be biased by differences in socioeconomic backgrounds.
Published: 2020

16. Search for protective genetic variants in Alzheimer disease in the U.S. Midwestern Amish

Author: M. Denise Fuzzell, Michael Prough, Renee Laux, Laura Caywood, Kristy Miskimen, Audrey Lynn, Jason E. Clouse, Alan J. Lerner, Jane L. Sewell, Sharlene D. Herington, Jonathan L. Haines, Margaret A. Pericak-Vance, Michael L. Cuccaro, Paula Ogrocki, Leighanne R. Main, Sarada Fuzzell, Jeffery M. Vance, Yeunjoo E. Song, Bill Scott, and Larry D. Adams
Subjects: Genetics, Epidemiology, Health Policy, Genetic variants, Disease, Biology, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, Neurology (clinical), Geriatrics and Gerontology, Alzheimer's disease
Published: 2020

17. Longitudinal assessment of cognitive decline in the Amish

Author: Kristy Miskimen, William K. Scott, Jeffery M. Vance, Paula Ogrocki, M. Denise Fuzzell, Margaret A. Pericak-Vance, Sarada Fuzzell, Larry D. Adams, Sharlene D. Herington, Sherri D. Miller, Jonathan L. Haines, Laura Caywood, Jason E. Close, Michael L. Cuccaro, Alan J. Lerner, Jane L. Sewell, Michael Prough, Jairo Ramos, Yeunjoo E. Song, Susan Slifer, and Renee Laux
Subjects: Epidemiology, business.industry, Health Policy, Neuropsychology, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Medicine, Dementia, Neurology (clinical), Geriatrics and Gerontology, Cognitive decline, business, Clinical psychology
Published: 2020

18. Joint linkage and association mapping of preserved cognition in the old‐order Amish

Author: Susan Slifer, Sarada Fuzzell, Jeffery M. Vance, Renee Laux, Sharlene D. Herington, Paula Ogrocki, Jonathan L. Haines, Leighanne R. Main, Jairo Ramos, Alan J. Lerner, Jane L. Sewell, Michael L. Cuccaro, James M. Jaworski, Sherri D. Miller, Larry D. Adams, Yeunjoo E. Song, William K. Scott, Kristy Miskimen, Jason E. Clouse, M. Denise Fuzzell, Laura Caywood, Margaret A. Pericak-Vance, and Michael Prough
Subjects: Linkage (software), Epidemiology, Health Policy, Cognition, Genealogy, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Old Order Amish, Neurology (clinical), Geriatrics and Gerontology, Association mapping, Psychology, Joint (geology)
Published: 2020

19. 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

20. Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial

Author: Jennifer Martindale-Adams, Alfred K. Cheung, Gordon J. Chelune, Carolyn H Still, Linda O. Nichols, Meng-Kang Hsieh, Michael Crowe, Daniel E. Weiner, Sarah A. Gaussoin, Jeff D. Williamson, Maryjo Cleveland, Clinton B. Wright, Lenore J. Launer, William C. Cushman, R. Nick Bryan, Darrin Harris, Claudia S. Moy, Manjula Kurella Tamura, Mahboob Rahman, Alan J. Lerner, Jackson T. Wright, Cora E. Lewis, Jennifer Walker, Virginia G. Wadley, Karen C. Johnson, Paul K. Whelton, Paula Ogrocki, Valerie M. Wilson, Guray Erus, Mark A. Supiano, Nancy Woolard, Alexander P. Auchus, Joni K. Snyder, Larry J. Fine, Ilya M. Nasrallah, Stephen R. Rapp, Kaycee M. Sink, Lisa Desiderio, Paul L. Kimmel, Nicholas M. Pajewski, David M. Reboussin, Christos Davatzikos, Jeffrey A. Cutler, Suzanne Oparil, Laura H. Coker, Bonnie C. Sachs, and Michael V. Rocco
Subjects: Male, medicine.medical_specialty, Randomization, Blood Pressure, 01 natural sciences, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Dementia, Humans, Cognitive Dysfunction, 030212 general & internal medicine, 0101 mathematics, Stroke, Antihypertensive Agents, Aged, Proportional Hazards Models, Aged, 80 and over, business.industry, Standard treatment, 010102 general mathematics, Hazard ratio, General Medicine, Middle Aged, medicine.disease, Blood pressure, Cardiovascular Diseases, Ambulatory, Hypertension, Female, business, Follow-Up Studies
Abstract: Importance There are currently no proven treatments to reduce the risk of mild cognitive impairment and dementia. Objective To evaluate the effect of intensive blood pressure control on risk of dementia. Design, Setting, and Participants Randomized clinical trial conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diabetes or history of stroke. Randomization began on November 8, 2010. The trial was stopped early for benefit on its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. The final date for follow-up of cognitive outcomes was July 22, 2018. Interventions Participants were randomized to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment group; n = 4678) or less than 140 mm Hg (standard treatment group; n = 4683). Main Outcomes and Measures The primary cognitive outcome was occurrence of adjudicated probable dementia. Secondary cognitive outcomes included adjudicated mild cognitive impairment and a composite outcome of mild cognitive impairment or probable dementia. Results Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 8563 (91.5%) completed at least 1 follow-up cognitive assessment. The median intervention period was 3.34 years. During a total median follow-up of 5.11 years, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1000 person-years; hazard ratio [HR], 0.83; 95% CI, 0.67-1.04). Intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97). Conclusions and Relevance Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of less than 140 mm Hg did not result in a significant reduction in the risk of probable dementia. Because of early study termination and fewer than expected cases of dementia, the study may have been underpowered for this end point. Trial Registration ClinicalTrials.gov Identifier:NCT01206062
Published: 2019

21. 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

22. 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

23. 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

24. 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

25. Association of Intensive vs Standard Blood Pressure Control With Cerebral White Matter Lesions

Author: Daniel E. Weiner, Larry J. Fine, Ilya M. Nasrallah, Jennifer Martindale-Adams, Claudia S. Moy, Manjula Kurella Tamura, Laura H. Coker, Karen C. Johnson, Virginia G. Wadley, Bonnie C. Sachs, David M. Reboussin, Christos Davatzikos, Gordon J. Chelune, Linda O. Nichols, Jeffrey A. Cutler, Sarah A. Gaussoin, Alan J. Lerner, Suzanne Oparil, Michael Crowe, Joni K. Snyder, Paula Ogrocki, Paul K. Whelton, Valerie M. Wilson, Alfred K. Cheung, Jeff D. Williamson, Guray Erus, Mark A. Supiano, Maryjo Cleveland, Nancy Woolard, Alexander P. Auchus, Michael V. Rocco, Clinton B. Wright, Cora E. Lewis, William C. Cushman, Lenore J. Launer, Jimit Doshi, Nicholas M. Pajewski, R. Nick Bryan, Mahboob Rahman, Darrin Harris, Jackson T. Wright, Jennifer Walker, Lisa Desiderio, Paul L. Kimmel, Carolyn H Still, Stephen R. Rapp, and Kaycee M. Sink
Subjects: medicine.medical_specialty, Randomization, 01 natural sciences, law.invention, Lesion, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Diabetes mellitus, medicine, 030212 general & internal medicine, 0101 mathematics, Stroke, Original Investigation, business.industry, Standard treatment, 010102 general mathematics, General Medicine, medicine.disease, Hyperintensity, Blood pressure, Cardiology, medicine.symptom, business
Abstract: IMPORTANCE: The effect of intensive blood pressure lowering on brain health remains uncertain. OBJECTIVE: To evaluate the association of intensive blood pressure treatment with cerebral white matter lesion and brain volumes. DESIGN, SETTING, AND PARTICIPANTS: A substudy of a multicenter randomized clinical trial of hypertensive adults 50 years or older without a history of diabetes or stroke at 27 sites in the United States. Randomization began on November 8, 2010. The overall trial was stopped early because of benefit for its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. Brain magnetic resonance imaging (MRI) was performed on a subset of participants at baseline (n = 670) and at 4 years of follow-up (n = 449); final follow-up date was July 1, 2016. INTERVENTIONS: Participants were randomized to a systolic blood pressure (SBP) goal of either less than 120 mm Hg (intensive treatment, n = 355) or less than 140 mm Hg (standard treatment, n = 315). MAIN OUTCOMES AND MEASURES: The primary outcome was change in total white matter lesion volume from baseline. Change in total brain volume was a secondary outcome. RESULTS: Among 670 recruited patients who had baseline MRI (mean age, 67.3 [SD, 8.2] years; 40.4% women), 449 (67.0%) completed the follow-up MRI at a median of 3.97 years after randomization, after a median intervention period of 3.40 years. In the intensive treatment group, based on a robust linear mixed model, mean white matter lesion volume increased from 4.57 to 5.49 cm(3) (difference, 0.92 cm(3) [95% CI, 0.69 to 1.14]) vs an increase from 4.40 to 5.85 cm(3) (difference, 1.45 cm(3) [95% CI, 1.21 to 1.70]) in the standard treatment group (between-group difference in change, −0.54 cm(3) [95% CI, −0.87 to −0.20]). Mean total brain volume decreased from 1134.5 to 1104.0 cm(3) (difference, −30.6 cm(3) [95% CI, −32.3 to −28.8]) in the intensive treatment group vs a decrease from 1134.0 to 1107.1 cm(3) (difference, −26.9 cm(3) [95% CI, 24.8 to 28.8]) in the standard treatment group (between-group difference in change, −3.7 cm(3) [95% CI, −6.3 to −1.1]). CONCLUSIONS AND RELEVANCE: Among hypertensive adults, targeting an SBP of less than 120 mm Hg, compared with less than 140 mm Hg, was significantly associated with a smaller increase in cerebral white matter lesion volume and a greater decrease in total brain volume, although the differences were small. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01206062
Published: 2019

26. P3-135: PROTECTIVE GENETIC VARIANTS IN THE MIDWESTERN AMISH

Author: Bill Scott, Jonathan L. Haines, Kristy Miskimen, Jeffery M. Vance, Leighanne R. Main, M. Denise Fuzzell, Michael Prough, Renee Laux, Yeunjoo E. Song, Margaret A. Pericak-Vance, Michelle C. Disher, Sarada Fuzzell, Michael L. Cuccaro, Paula Ogrocki, Alan J. Lerner, Jane L. Sewell, and Laura Caywood
Subjects: Genetics, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Genetic variants, Neurology (clinical), Geriatrics and Gerontology, Biology
Published: 2019

27. P3-140: PROTECTIVE EFFECT OF EDUCATION ON COGNITIVE FUNCTION IN THE OLD ORDER AMISH

Author: M. Denise Fuzzell, William K. Scott, Patrice L. Whitehead, Margaret A. Pericak-Vance, Yeunjoo E. Song, Michael Prough, Alan J. Lerner, Larry D. Adams, Sarada Fuzzell, Kristy Miskimen, Renee Laux, Michael L. Cuccaro, Paula Ogrocki, Jairo Ramos, Laura Caywood, and Jeffery M. Vance
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Old Order Amish, Cognition, Neurology (clinical), Geriatrics and Gerontology, Psychology, Developmental psychology
Published: 2019

28. 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

29. P1‐368: Quantitative Temporal Dynamics of Semantic Fluency in Older Adults

Author: Wojbor A. Woyczyński, Curtis Tatsuoka, Martha Sajatovic, Paula Ogrocki, Elisabeth Welter, Johnny Sams, Alan J. Lerner, Kathleen A. Smyth, Frances M. Lissemore, and Steven Lenio
Subjects: Epidemiology, Health Policy, Semantic fluency, 030227 psychiatry, 03 medical and health sciences, Psychiatry and Mental health, Cellular and Molecular Neuroscience, 0302 clinical medicine, Developmental Neuroscience, Dynamics (music), Neurology (clinical), Geriatrics and Gerontology, Psychology, 030217 neurology & neurosurgery, Cognitive psychology
Published: 2016

30. 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

31. Subjective preference for lamotrigine or topiramate in healthy volunteers: Relationship to cognitive and behavioral functioning

Author: Mike R. Schoenberg, David W. Loring, P. G. Ray, Mary Ann Werz, Rina Kaul-Gupta, Kimford J. Meador, and Paula Ogrocki
Subjects: Adult, Male, Topiramate, Fructose, Neuropsychological Tests, Lamotrigine, Profile of mood states, Behavioral Neuroscience, Epilepsy, Cognition, Double-Blind Method, Memory, medicine, Humans, Attention, Behavior, Cross-Over Studies, Triazines, Neuropsychology, Middle Aged, medicine.disease, Crossover study, Preference, Mood, Neurology, Patient Satisfaction, Quality of Life, Anticonvulsants, Female, Neurology (clinical), Psychology, medicine.drug, Clinical psychology
Abstract: Objective Outcomes research emphasizes patient self-assessment and preferences in optimizing treatment. We previously showed that lamotrigine produces significantly less cognitive and behavioral impairment compared with topiramate. In the current study we extend these observations to subject self-report of preference for lamotrigine or topiramate independent of potentially confounding effects of seizures or seizure control. Additionally, drug preference was related to effects of lamotrigine and topiramate on objective neuropsychological tests as well as self-perception on behavioral instruments. Methods Thirty-seven healthy volunteers completed a double-blind, randomized crossover design incorporating two 12-week treatment periods of lamotrigine and topiramate each titrated to a dose of 300 mg/day. Evaluation of 23 objective neuropsychological and 15 subjective behavioral measures occurred at four times: pretreatment baseline, first treatment, second treatment, and posttreatment baseline. Preference for lamotrigine or topiramate was assessed, while blinding was maintained, at the final study visit when each subject was asked which drug he or she would prefer to take. Results A large majority (70%) preferred lamotrigine, 16% stated preference for topiramate, and 14% had no preference (drugs equivalent). Consistent with preference, those preferring lamotrigine performed better on 19 of 23 objective and 13 of 15 subjective behavioral measurements while on lamotrigine. Inconsistent with preference, subjects preferring topiramate performed better on 19 of 23 objective and 9 of 15 subjective behavioral measures while on lamotrigine. Topiramate preference also did not correlate with IQ, serum concentration, body mass index, age, or gender. Topiramate preference did relate to responses on the Profile of Mood States. Conclusion Lamotrigine was preferred by the majority of subjects, congruent with objective neuropsychological and subjective behavioral measures. In contrast, for those stating a preference for topiramate the results on objective neuropsychological measures were impaired while fewer complaints were noted on the Profile of Mood States. This suggests that preference for topiramate may be determined by an effect on mood.
Published: 2006

32. Associations Between Dementia/Mild Cognitive Impairment and Cognitive Performance and Activity Levels in Youth

Author: Concepcion E. Santillan, Paula Ogrocki, Janet D. Larsen, Milton E. Strauss, Kathleen A. Smyth, Thomas Fritsch, and McKee J. McClendon
Subjects: Geriatrics, Gerontology, medicine.medical_specialty, Intelligence quotient, business.industry, Cognitive disorder, Cognition, Odds ratio, medicine.disease, Informant Questionnaire on Cognitive Decline in the Elderly, medicine, Dementia, Effects of sleep deprivation on cognitive performance, Geriatrics and Gerontology, business
Abstract: Objectives: To study the associations between dementia/mild cognitive impairment (MCI) and cognitive performance and activity levels in youth. Design: Retrospective cohort study. Setting: Research volunteers living throughout the United States. Participants: A total of 396 persons (mean age 75) who were graduates of the same high school in the mid-1940s. Measurements: Adolescent intelligence quotient (IQ) scores were gathered from archived student records, and activity levels were determined from yearbooks. A two-stage telephone screening procedure (Modified Telephone Interview for Cognitive Status or Informant Questionnaire on Cognitive Decline in the Elderly followed by Dementia Questionnaire) was used to determine adult cognitive status. Data were analyzed using logistic regression to model the risk of cognitive impairment (dementia/MCI) versus no cognitive impairment as a function of IQ and activity level, adjusting for sex and education. Results: High adolescent IQ and greater activity level were each independently associated with a lower risk for dementia/MCI (odds ratio (OR) for a 1-standard deviation increase in IQ=0.51, 95% confidence interval (CI)=0.32–0.79; OR for a unit increase in activity=0.32, 95% CI=0.12–0.84). No association was found between sex or education and adult cognitive status in this model. Conclusion: High IQ and greater activity levels in youth reduce the risk for cognitive impairments in aging. The mechanism(s) underlying these associations are unknown, but intelligence may be a marker for cognitive/neurological “reserve,” and involvement in activities may contribute to “reserve.” Early neuropathology and ascertainment bias are also possible explanations for the observed associations.
Published: 2005

33. Influence of Probable Alzheimer's Disease on Multiplication Verification and Production Abstract

Author: Sandrine Duverne, Barbara Bucur, Patrick Lemaire, Raymond E. Sanders, Paula Ogrocki, and Philip A. Allen
Subjects: Psychiatry and Mental health, medicine.medical_specialty, Neuropsychology and Physiological Psychology, Group differences, Younger adults, medicine, Experimental and Cognitive Psychology, Multiplication, Disease, Geriatrics and Gerontology, Audiology, Psychology, Developmental psychology
Abstract: We compared the multiplication verification and production performances of healthy younger (n = 20) and older (n = 20) adults to that of mildly demented (Mini Mental Status Exam range: 19–27) individuals diagnosed with probable Alzheimer's disease (n = 18). While healthy older adults and Alzheimer's patients were slower than younger adults, the older adults actually showed significantly smaller problem-size effects for verification and production reaction time (RT) tasks. These results suggest that retrieval of multiplication fact knowledge from long-term memory for multiplicands greater than zero remains largely intact in mildly demented individuals diagnosed with probable Alzheimer's discase, although these individuals may have more difficulty with volitional retrieval because group differences were larger for some production analyses (require volitional retrieval) than for verification analyses (simply requires familiarity). However, for problems involving zero multiplicands (but not 1’s), hea...
Published: 2005

34. Effects of Educational Attainment and Occupational Status on Cognitive and Functional Decline in Persons With Alzheimer-Type Dementia

Author: Kathleen A. Smyth, Paula Ogrocki, Thomas Fritsch, and McKee J. McClendon
Subjects: Male, Gerontology, Activities of daily living, Occupational prestige, Alzheimer Disease, Risk Factors, Activities of Daily Living, medicine, Humans, Functional ability, Cognitive decline, Aged, Aged, 80 and over, Career Choice, Cognitive disorder, Repeated measures design, Cognition, medicine.disease, Educational attainment, Psychiatry and Mental health, Clinical Psychology, Educational Status, Female, Geriatrics and Gerontology, Mental Status Schedule, Psychology
Abstract: Researchers have suggested that educational attainment and occupational status—indicators of cognitive and/or neurologic “reserve”—can help persons compensate for clinical manifestations of Alzheimer's disease (AD), such as the rates of cognitive and functional decline. The effects of educational attainment on rates of decline could be “direct” (independent of occupational status), “indirect” (working through occupational status), or both. We used multilevel analysis for repeated measures to study the effects of educational attainment and occupational status on rates of decline in cognition (Mini-Mental State Examination, MMSE) and function (Cleveland Scale for Activities of Daily Living). Subject included persons with “probable” or “possible” AD, drawn from our Alzheimer's Disease Research Center registry (N = 482 in the analysis of cognitive decline, and N = 450 in the analysis of functional decline). When controlling for year of birth, gender, ethinicity, and duration of illness, we found that there was an inverse relationship between number of years of education and rate of decline in MMSE, but effects of occupational status were not significant. This implies a “direct” effect of education on decline in MMSE, but no “indirect” effect through occupational status. Neither educational attainment nor occupational status affected rate of decline in functional ability. We conclude that education slows the rate of cognitive decline in persons with AD, but not through its impact on occupational status. Thus the protective effects of reserve may be established early in life, before people enter the workforce.
Published: 2002

35. Quality of Life and Deficit Identification in Dementia

Author: Paula Ogrocki, Elisabeth Koss, Kathleen A. Smyth, Peter J. Whitehouse, David S. Geldmacher, and Marcia M. Neundorfer
Subjects: Sociology and Political Science, 05 social sciences, Psychological intervention, General Social Sciences, 050109 social psychology, General Medicine, Interpersonal communication, medicine.disease, 030227 psychiatry, 03 medical and health sciences, Identification (information), 0302 clinical medicine, Quality of life (healthcare), mental disorders, medicine, Dementia, 0501 psychology and cognitive sciences, Aggregate level, Psychology, Clinical psychology
Abstract: Numerous studies have examined self-identification of deficits in persons with dementia. Few of these studies consider the influence of interpersonal and social factors on deficit identification, and most focus on whether or why deficits are ‘underreported’ by persons with dementia. In our studies, we found considerable variation in deficit identification within and among persons with dementia, and some ‘overreporting’ of deficits in comparison with caregiver reports across all of the domains studied. Thus, focusing on ‘underreporting’ and aggregate level data neglects information that could be important to measuring and understanding quality of life in dementia. Current approaches to measuring and understanding quality of life in dementia make divergent assumptions about the impact of deficit identification. Emerging phenomenological perspectives suggest that proactive interventions that treat deficit identification as an interpersonal and social challenge inherent in the experience of dementia would enhance the quality of life of caregiving dyads.
Published: 2002

36. Five-months-postoperative neuropsychological outcome from a pilot prospective randomized clinical trial of thalamic deep brain stimulation for Tourette syndrome

Author: Robert J. Maciunas, Christina M. Whitney, Paula Ogrocki, Brian N. Maddux, Mike R. Schoenberg, David E. Riley, and Deborah J. Gould
Subjects: Adult, Male, medicine.medical_specialty, Deep brain stimulation, Tics, Personality Inventory, Visual Analog Scale, medicine.medical_treatment, Deep Brain Stimulation, Pilot Projects, Audiology, Neuropsychological Tests, Tourette syndrome, Young Adult, Thalamus, medicine, Verbal fluency test, Humans, Psychomotor learning, Analysis of Variance, medicine.diagnostic_test, business.industry, General Medicine, Neuropsychological test, medicine.disease, Anesthesiology and Pain Medicine, Mood, Treatment Outcome, Neurology, Quality of Life, Anxiety, Female, Neurology (clinical), medicine.symptom, business, Cognition Disorders, Clinical psychology, Follow-Up Studies, Tourette Syndrome
Abstract: Objective Tourette syndrome (TS) is a neuropsychiatric disorder presenting with motor and/or sonic tics associated with frontostriatal dysfunction. This study provided pilot data of the neuropsychological safety of bilateral thalamic deep brain stimulation (DBS) to treat medication-refractory TS in adults. Method This study used a repeated-measures design with pretest and 3-month follow-up from start of continuous bilateral DBS. Five male patients underwent DBS surgery for medically refractory TS. Repeated-measures ANOVA was used to evaluate for any change in neuropsychological test scores, employing a false discovery rate. Outcome measures included 14 neuropsychological tests assessing psychomotor speed, attention, memory, language, visuoconstructional, and executive functions, as well as subjective mood ratings of depression and anxiety. Results Average age was 28.2 years (SD = 7.5) with 12–17 years of education. Participants were disabled by tics, with a tic frequency of 50–80 per minute before surgery. At baseline, subjects' cognitive function was generally average, although mild deficits in sequencing and verbal fluency were present, as were clinically mild obsessive–compulsive symptoms. At 3 months of continuous DBS (5 months after implantation), 3 of 5 participants had clinical reductions in motor and sonic tics. Cognitive scores generally remained stable, but declines of moderate to large effect size (Cohen's d > 0.6) in verbal fluency, visual immediate memory, and reaction time were observed. Fewer symptoms of depression and anxiety, as well as fewer obsessions and compulsions, were reported after 3 months of continuous high-frequency DBS. Conclusions Bilateral centromedian–parafascicular thalamic DBS for medically refractory TS shows promise for treatment of medically refractory TS without marked neuropsychological morbidity. Symptoms of depression and anxiety improved.
Published: 2014

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

Author: Mary M. Laubinger, Po H. Lu, M. Saleem Ismail, Alan J. Lerner, Paul Malloy, Daniel C. Marson, Pierre N. Tariot, Adam S. Fleisher, Neill R Graff-Radford Mbbch, Vernice Bates, Jeffrey M. Burns, Robert B. Santulli, Maria Kataki, Kris A. Johnson, Henry Rusinek, Nick C. Fox, Ronald C. Petersen, Matt A. Bernstein, Heather Anderson, Janet S. Cellar, Godfrey D. Pearlson, Mark A. Mintun, Karen Crawford, Stephen Salloway, Owen Carmichael, Kaycee M. Sink, Howard Chertkow, Jeff D. Williamson, Ann Marie Hake, Teresa Villena, Scott Turner, George Marzloff, Daniel Varon, Anil Nair, Martin R. Farlow, Yaakov Stern, Javier Villanueva-Meyer, Kathleen Johnson, Martha G. MacAvoy, Daniel H.S. Silverman, Marjorie E. Marenberg, Jacobo Mintzer, Ranjan Duara, Ronald A. Cohen, Munir Chowdhury, Bruce L. Miller, Charles DeCarli, Dzintra Celmins, Stephen Correia, Sonia Pawluczyk, Paul S. Aisen, Heather Johnson, Gaby Thai, Paul J. Wang, William J. Jagust, Anthony Gamst, Adrian Preda, Jaimie Toroney, Allyson C. Rosen, Chris Hosein, Michele Assaly, Neil Buckholtz, Christopher M. Clark, Hillel Grossman, Stephanie Reeder, Ging-Yuek Robin Hsiung, John A. Rogers, Wes Ashford, Scott C. Neu, Jennifer Richard, Karen S. Anderson, Michael Borrie, George Bartzokis, Marilyn S. Albert, Brian R. Ott, Barry A. Hendin, Dick Trost, Michael D. Devous, Ramon Diaz-Arrastia, Chuang-Kuo Wu, Helen Vanderswag, Jeffrey R. Petrella, Susan De Santi, Jeffrey Kaye, Randall Griffith, Howard Feldman, Catherine Mc-Adams-Ortiz, Bryan M. Spann, Donald Connor, Francine Parfitt, Ruth A. Mulnard, P. Murali Doraiswamy, Raj C. Shah, M.-Marsel Mesulam, Howard J. Rosen, Donna Munic, Marilyn Aiello, Robert C. Green, Laurel A. Beckett, Cynthia M. Carlsson, Marwan N. Sabbagh, Michael C. Donohue, John C. Morris, Donna M. Simpson, Peter A. Hardy, James B. Brewer, Charles Bernick, Cheuk Y. Tang, Leon Hudson, Sanjay Asthana, Alice D. Brown, Kristen Martin-Cook, David G. Clark, Amanda L. Benincasa, T-Y Lee, Seema Mirje, Charles D. Smith, Lon S. Schneider, Nancy Collins Johnson, Christopher H. van Dyck, Joseph F. Quinn, Steven G. Potkin, Sandra Jacobson, Ronald G. Thomas, Kelly E. Behan, Barry W. Rovner, Anders M. Dale, Norbert Schuff, Howard Bergman, Arthur W. Toga, Andrew Kertesz, Horacio Capote, Keith A. Johnson, Mony J. de Leon, Sandra E. Black, Dan Bandy, Karen L. Bell, Leylade Toledo-Morrell, Allan I. Levey, Connie Brand, Paul M. Thompson, Julia Pedroso, Scott Herring, Dana Nguyen, Oscar L. Lopez, Judith L. Heidebrink, Curtis A. Given, Reisa A. Sperling, Simon P. Graham, Danielle J Harvey, Earl A. Zimmerman, Sara Dolen, John Kornak, Walter Martinez, Ronald J. Killiany, Smita Kittur, Holly Soares, Paula Ogrocki, Joanne L. Lord, Jared R. Tinklenberg, Lawrence S. Honig, Kewei Chen, Carl H. Sadowsky, Joel P. Felmlee, Magdalena Korecka, Jessica Englert, Peggy Roberts, Michelle Rainka, Clifford R. Jack, Annapurni Jayam-Trouth, Alexander Norbash, Sterling C. Johnson, Curtis B. Caldwell, MaryAnn Oakley, Gene E. Alexander, Dorene M. Rentz, Tatiana Foroud, James J. Lah, Cassie Pham, Virginia M.-Y. Lee, Franklin Watkins, T. J. Montine, Douglas W. Scharre, Sam Gandy, Thomas O. Obisesan, Steven Potkin, Li Shen, Jessica Nunez, Andrew J. Saykin, Raymond Y. Lo, Evan Fletcher, Sarah Walter, Stacy Schneider, Rob Bartha, and Rachelle S. Doody
Subjects: Oncology, medicine.medical_specialty, Longitudinal study, Patient Dropouts, tau Proteins, Neuropsychological Tests, Logistic regression, Developmental psychology, Cohort Studies, Alzheimer Disease, Fluorodeoxyglucose F18, Risk Factors, Internal medicine, mental disorders, medicine, Dementia, Humans, Cognitive Dysfunction, Longitudinal Studies, Homocysteine, Amyloid beta-Peptides, Dementia, Vascular, medicine.disease, Missing data, Magnetic Resonance Imaging, Peptide Fragments, Logistic Models, Research Design, Positron-Emission Tomography, Biomarker (medicine), Neurology (clinical), Alzheimer's disease, Psychology, Biomarkers, Alzheimer's Disease Neuroimaging Initiative, Cohort study
Abstract: Objective: To investigate predictors of missing data in a longitudinal study of Alzheimer disease (AD). Methods: The Alzheimer9s Disease Neuroimaging Initiative (ADNI) is a clinic-based, multicenter, longitudinal study with blood, CSF, PET, and MRI scans repeatedly measured in 229 participants with normal cognition (NC), 397 with mild cognitive impairment (MCI), and 193 with mild AD during 2005–2007. We used univariate and multivariable logistic regression models to examine the associations between baseline demographic/clinical features and loss of biomarker follow-ups in ADNI. Results: CSF studies tended to recruit and retain patients with MCI with more AD-like features, including lower levels of baseline CSF Aβ 42 . Depression was the major predictor for MCI dropouts, while family history of AD kept more patients with AD enrolled in PET and MRI studies. Poor cognitive performance was associated with loss of follow-up in most biomarker studies, even among NC participants. The presence of vascular risk factors seemed more critical than cognitive function for predicting dropouts in AD. Conclusion: The missing data are not missing completely at random in ADNI and likely conditional on certain features in addition to cognitive function. Missing data predictors vary across biomarkers and even MCI and AD groups do not share the same missing data pattern. Understanding the missing data structure may help in the design of future longitudinal studies and clinical trials in AD.
Published: 2012

38. Network graph analysis of category fluency testing

Author: Peter J. Thomas, Paula Ogrocki, and Alan J. Lerner
Subjects: Power graph analysis, Male, Theoretical computer science, Cognitive Neuroscience, Word Association Tests, Neuropsychological Tests, Semantics, Interconnectedness, Fluency, Alzheimer Disease, Verbal fluency test, Cluster Analysis, Humans, Aged, Psychiatric Status Rating Scales, Communication, business.industry, Graph theory, General Medicine, Psychiatry and Mental health, Neuropsychology and Physiological Psychology, Categorization, Data Interpretation, Statistical, Female, Psychology, business, Cognition Disorders, Algorithms, Network analysis
Abstract: Category fluency is impaired early in Alzheimer disease (AD). Graph theory is a technique to analyze complex relationships in networks. Features of interest in network analysis include the number of nodes and edges, and variables related to their interconnectedness. Other properties important in network analysis are "small world properties" and "scale-free" properties. The small world property (popularized as the so-called "6 degrees of separation") arises when the majority of connections are local, but a number of connections are to distant nodes. Scale-free networks are characterized by the presence of a few nodes with many connections, and many more nodes with fewer connections.To determine if category fluency data can be analyzed using graph theory. To compare normal elderly, mild cognitive impairment (MCI) and AD network graphs, and characterize changes seen with increasing cognitive impairment.Category fluency results ("animals" recorded over 60 s) from normals (n=38), MCI (n=33), and AD (n=40) completing uniform data set evaluations were converted to network graphs of all unique cooccurring neighbors, and compared for network variables.For Normal, MCI and AD, mean clustering coefficients were 0.21, 0.22, 0.30; characteristic path lengths were 3.27, 3.17, and 2.65; small world properties decreased with increasing cognitive impairment, and all graphs showed scale-free properties. Rank correlations of the 25 commonest items ranged from 0.75 to 0.83. Filtering of low-degree nodes in normal and MCI graphs resulted in properties similar to the AD network graph.Network graph analysis is a promising technique for analyzing changes in category fluency. Our technique results in nonrandom graphs consistent with well-characterized properties for these types of graphs.
Published: 2009

39. P3‐152: Mapping of Alzheimer's disease stages using the MMSE: Effects of ehnicity and education

Author: Susie A. Sami, Alan J. Lerner, Kathleen A. Smyth, Mendel E. Singer, Zimbul Albo, Paula Ogrocki, and McKee K. McClendon
Subjects: Gerontology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, business.industry, Disease stages, Health Policy, Medicine, Neurology (clinical), Geriatrics and Gerontology, business
Published: 2008

40. Factors affecting usage patterns of memantine in Alzheimer disease

Author: McKee J. McClendon, Alan J. Lerner, Susie A. Sami, Paula Ogrocki, Kathryn Betts Adams, and Kathleen A. Smyth
Subjects: Male, medicine.medical_specialty, macromolecular substances, Bioinformatics, Severity of Illness Index, Central nervous system disease, Degenerative disease, Alzheimer Disease, Memantine, medicine, Humans, Practice Patterns, Physicians', Psychiatry, Aged, Retrospective Studies, Aged, 80 and over, Cognitive disorder, Antagonist, Glutamate receptor, Middle Aged, medicine.disease, Drug Utilization, United States, Psychiatry and Mental health, Clinical Psychology, Binomial Distribution, NMDA receptor, Female, Geriatrics and Gerontology, Alzheimer's disease, Psychology, Gerontology, Excitatory Amino Acid Antagonists, medicine.drug
Abstract: Memantine is approved by the US Food and Drug Administration for the treatment of moderate to severe Alzheimer disease (AD). We investigated the frequency and variables associated with its use in mild to moderate/severe AD as defined by criteria involving the Mini-Mental Status Examination (MMSE) and Clinical Dementia Rating (CDR) scale. Consecutive possible and probable AD patients seen at our research center from November 2003 to December 2006 were included. Individuals were classified as mild dementia either by CDR=1 or MMSEor=15, using criteria derived in part from the pivotal trials of memantine used for its approval by the Food and Drug Administration. Of 117 patients, 37% of those with mild AD by MMSE criterion (total N=94), and 38% of those with mild AD by CDR criterion (total N=86) used memantine. Logistic regression was used to simultaneously estimate the odds ratios (ORs) of the likelihood of memantine usage associated with a set of predictor variables. Lower MMSE was associated with a greater likelihood of using memantine independent of CDR [ORMMSE=7.45, 95% confidence interval (CI)=1.50-37.05]; CDR was not significantly related to memantine use. Controlling both MMSE and CDR, Whites were more likely to use memantine than African Americans (OR=6.47, 95% CI=1.25-33.39). Patients who used other antidementia medications were more likely to use memantine than those who did not (OR=3.15, 95% CI=0.995-9.97). Eight other patient characteristics were not significant predictors. Use of memantine in mild AD was common. Patterns of memantine usage are complex and deserve further study in a larger sample because of their implications for medical system cost, equitable access to care, and risk of drug interactions.
Published: 2008

41. Influence of mild cognitive impairment on visual word recognition

Author: Philip A. Allen, Kevin P. Kaut, Paula Ogrocki, and Aryn Harrison Bush
Subjects: Male, medicine.medical_specialty, Experimental and Cognitive Psychology, Normal aging, Audiology, Neuropsychological Tests, Severity of Illness Index, Vocabulary, Alzheimer Disease, Lexical decision task, medicine, Reaction Time, Humans, Cognitive impairment, Aged, Visual word recognition, Aged, 80 and over, Cognition, Recognition, Psychology, Middle Aged, Psychiatry and Mental health, Neuropsychology and Physiological Psychology, Younger adults, Visual Perception, Female, Geriatrics and Gerontology, Psychology, Cognition Disorders, Cognitive psychology
Abstract: The present study examined the effects of normal aging and mild cognitive impairment (MCI) on visual word recognition. Madden et al. (1999) reported evidence of general slowing of cognitive processes in Alzheimer's disease (AD) patients relative to younger adults and healthy older adults using a lexical decision task. It was of interest to determine whether similar effects would be observed in MCI patients relative to healthy younger and older adults. We extended the lexical decision task paradigm developed by Allen et al. (2004b) on younger adults to an examination of the effect(s) of MCI on visual word recognition. Results from the present study showed that healthy older adults and MCI patients performed similarly. That is, both groups took longer than younger adults to process words presented in mixed-case than in consistent-case letters. Mild cognitive impairment patients, however, responded significantly more slowly than healthy older adults across all lexical decision task conditions and showed a trend toward larger case-mixing effects than healthy older adults, which suggests that MCI may result in poorer analytic processing ability. Based on the current findings, evidence of a generalized slowing of cognitive processes using a standard lexical decision task can be expanded to include not only AD patients, but also the preclinical stages of the disease as well.
Published: 2007

42. The Alzheimer's Disease Centers' Neuropsychological Database Initiative: A Resource for Alzheimer's Disease Prevention Trials

Author: Leon J. Thal, Nancy Johnson, Jason Brandt, Richard C. Mohs, Paula Ogrocki, Walter A. Kukull, Joanne Green, Steven H. Ferris, Diane B. Howieson, Hyun T. Kim, Kathy Saine, Glenn E. Smith, Martha Storandt, Judith Saxton, Anthony Gamst, Michael Grundman, Frederick A. Schmitt, Michelle Papka, Rachelle S. Doody, Kathleen A. Welsh-Bohmer, and David P. Salmon
Subjects: medicine.medical_specialty, Resource (biology), business.industry, Neuropsychology, Medicine, Dementia, Disease prevention, Disease, Mild cognitive impairment (MCI), business, medicine.disease, Psychiatry
Published: 2003

43. Clinical differentiation of memory disorders in neurodegenerative disease

Author: Paula Ogrocki and Kathleen A. Welsh-Bohmer
Subjects: Parkinson's disease, Huntington's disease, medicine, Dementia, Semantic memory, Pick's disease, medicine.disease, Psychology, Vascular dementia, Neuroscience, Frontotemporal dementia, Progressive supranuclear palsy
Published: 1998

44. Marital quality, marital disruption, and immune function

Author: Janice K. Kiecolt-Glaser, Julie C. Stout, Laura D. Fisher, Carl E. Speicher, Ronald Glaser, and Paula Ogrocki
Subjects: Gerontology, Adult, Herpesvirus 4, Human, Time Factors, Separation (statistics), Marital separation, Marital relations, Immune system, Divorce, Humans, Lymphocytes, Risk factor, Marriage, Applied Psychology, Depression (differential diagnoses), Immunity, Cellular, Depression, Immunity, T-Lymphocytes, Helper-Inducer, Object Attachment, Killer Cells, Natural, Psychiatry and Mental health, Cohort, Female, Psychology, Human Females, Demography
Abstract: Marital disruption is associated with significant increases in a variety of psychologic and physical disorders. In order to examine psychologic and physiologic mediators, self-report data and blood samples were obtained from 38 married women and 38 separated/divorced women. Among married subjects, poorer marital quality was associated with greater depression and a poorer response on three qualitative measures of immune function. Women who had been separated 1 year or less had significantly poorer qualitative and quantitative immune function than their sociodemographically matched married counterparts. Among the separated/divorced cohort, shorter separation periods and greater attachment to the (ex)husband were associated with poorer immune function and greater depression. These data are consistent with epidemiologic evidence linking marital disruption with increased morbidity and mortality.
Published: 1987

45. Chronic stress and immunity in family caregivers of Alzheimer's disease victims

Author: Edwin C. Shuttleworth, Carl E. Speicher, Carol S. Dyer, Paula Ogrocki, Janice K. Kiecolt-Glaser, and Ronald Glaser
Subjects: Immunosuppression Therapy, Male, business.industry, Helper T lymphocyte, Family caregivers, Stressor, Loneliness, Disease, Middle Aged, Psychiatry and Mental health, Distress, Immune system, Alzheimer Disease, Immunology, Medicine, Humans, Chronic stress, Family, Female, medicine.symptom, business, Applied Psychology, Stress, Psychological, Clinical psychology
Abstract: Although acute stress has been associated with transient immunosuppression, little is known about the immunologic consequences of chronic stress in humans. In order to investigate possible health-related consequences of a long-term stressor, we obtained blood samples for immunologic and nutritional analyses and psychologic data from 34 family caregivers of Alzheimer's disease (AD) victims and 34 sociodemographically matched comparison subjects. Family caregivers for AD victims were more distressed than comparison subjects without similar responsibilities. Greater impairment in the AD victim was associated with greater distress and loneliness in caregivers. Caregivers had significantly lower percentages of total T lymphocytes and helper T lymphocytes than did comparison subjects, as well as significantly lower helper-suppressor cell ratios; caregivers also had significantly higher antibody titers to Epstein-Barr virus than did comparison subjects, presumably reflecting poorer cellular immune system control of the latent virus in caregivers. The percentages of natural killer cells and suppressor T lymphocytes did not differ significantly. These data suggest that chronically stressed AD family caregivers do not show immunologic or psychologic adaptation to the level of their well-matched age peers.
Published: 1987

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