Gray matter atrophy in patients with mild cognitive impairment/Alzheimer's disease over the course of developing delusions

Corinne E Fischer; Windsor Kwan-Chun Ting; Colleen P Millikin; Zahinoor Ismail; Tom A Schweizer; Alzheimer Disease Neuroimaging Initiative

doi:10.1002/gps.4291

Gray matter atrophy in patients with mild cognitive impairment/Alzheimer's disease over the course of developing delusions

Int J Geriatr Psychiatry. 2016 Jan;31(1):76-82. doi: 10.1002/gps.4291. Epub 2015 Mar 27.

Authors

Corinne E Fischer^{1

2}, Windsor Kwan-Chun Ting^{3

1}, Colleen P Millikin⁴, Zahinoor Ismail⁵, Tom A Schweizer^{3

1

6

7

8}; Alzheimer Disease Neuroimaging Initiative

Collaborators

Alzheimer Disease Neuroimaging Initiative:
Michael W Weiner, Paul Aisen, Ronald Petersen, Clifford R Jack Jr, 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, Davie Holtzman, M Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Robert C Green, Tom Montine, Ronald Petersen, Paul Aisen, Ronald G Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B Balasubramanian, Jennifer Mason, Iris Sim, Laurel Beckett, Danielle Harvey, Michael Donohue, Clifford R Jack Jr, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCarli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, William Jagust, Robert A Koeppe, Norm Foster, Eric M Reiman, Kewei Chen, Chet Mathis, Susan Landau, John Morris, Nigel J Cairns, Erin Householder, Lisa Taylor-Reinwald, Leslie M Shaw, John Q Trojanowki, Virginia Lee, Magdalena Korecka, Michal Figurski, Arthur W Toga, Karen Crawford, Scott Neu, Andrew J Saykin, Tatiana Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Michael W Weiner, Lean Thal, Zaven Khachaturian, Leon Thal, Neil Buckholtz, Michael W Weiner, Peter J Snyder, William Potter, Steven Paul, Marylyn Albert, Richard Frank, Zaven Khachaturian, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan M Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L Heidebrink, Joanne L Lord, Ronald Petersen, Sara S Mason, Colleen S Albers, David Knopman, Kris Johnson, Rachelle S Doody, Javier Villanueva-Meyer, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S Honig, Karen L Bell, Beau Ances, John C Morris, Maria Carroll, Mary L Creech, Erin Franklin, Mark A Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, Randall Griffith, David Clark, David Geldmacher, John Brockington, Erik Roberson, Marissa Natelson Love, Hillel Grossman, Effie Mitsis, Raj C Shah, Leyla de Toledo-Morrell, Ranjan Duara, Daniel Varon, Maria T Greig, Peggy Roberts, Marilyn Albert, Chiadi Onyike, Daniel D'Agostino 2nd, Stephanie Kielb, James E Galvin, Brittany Cerbone, Christina A Michel, Dana M Pogorelec, Henry Rusinek, Mony J de Leon, Lidia Glodzik, Susan De Santi, P Murali Doraiswamy, Jeffrey R Petrella, Salvador Borges-Neto, Terence Z Wong, Edward Coleman, Steven E Arnold, Jason H Karlawish, David 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, Ruth A Mulnard, Gaby Thai, Catherine Mc-Adams-Ortiz, 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, Tracy Kendall, Heather Johnson, Martin R Farlow, Ann Marie Hake, Brandy R Matthews, Jared R Brosch, Scott Herring, Cynthia Hunt, 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, Howard Feldman, Benita Mudge, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Keith A 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, Steven G Potkin, Adrian Preda, Dana Nguyen, Pierre Tariot, Anna Burke, Nadira Trncic, Adam Fleisher, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W Scharre, Maria Kataki, Anahita Adeli, 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, Leslie Gordineer, 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, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Elizabether Finger, Stephen Pasternak, Irina Rachinsky, John Rogers, Andrew Kertesz, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K Schultz, Laura L Boles Ponto, Hyungsub Shim, Karen Ekstam Smith, Norman Relkin, Gloria Chaing, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Michael W Weiner, Paul Aisen, Ronald Petersen, Robert C Green, Danielle Harvey, Clifford R Jack Jr, William Jagust, John C Morris, Andrew J Saykin, Leslie M Shaw, Arthur W Toga, John Q Trojanowki, Thomas Neylan, Jordan Grafman, Robert C Green, Tom Montine, Michael Weiner, Ronald Petersen, Paul Aisen, Ronald G Thomas, Michael Donohue, Devon Gessert, Tamie Sather, Melissa Davis, Rosemary Morrison, Gus Jiminez, Thomas Neylan, Jacqueline Hayes, Shannon Finley, Danielle Harvey, Michael Donohue, Clifford R Jack Jr, Matthew Bernstein, Bret Borowski, Jeff Gunter, Matt Senjem, Kejal Kantarci, Chad Ward, William Jagust, Robert A Koeppe, Norm Foster, Eric M Reiman, Kewei Chen, Susan Landau, John C Morris, Nigel J Cairns, Erin Householder, Leslie M Shaw, John Q Trojanowki, Virginia Lee, Magdalena Korecka, Michal Figurski, Arthur W Toga, Karen Crawford, Scott Neu, Andrew J Saykin, Tatiana M Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Michael W Weiner, Karl Friedl, Lon S Schneider, Sonia Pawluczyk, Mauricio Beccera, James Brewer, Helen Vanderswag, Yaakov Stern, Lawrence S Honig, Karen L Bell, Debra Fleischman, Konstantinos Arfanakis, Raj C Shah, Ranjan Duara, Daniel Varon, Maria T Greig, P Murali Doraiswamy, Jeffrey R Petrella, Olga James, Anton P Porsteinsson, Bonnie Goldstein, Kimberly S Martin, Ruth A Mulnard, Gaby Thai, Catherine McAdams-Ortiz, Jacobo Mintzer, Dino Massoglia, Olga Brawman-Mintzer, Carl Sadowsky, Walter Martinez, Teresa Villena, William Jagust, Susan Landau, Howard Rosen, David Perry, Raymond Scott Turner, Kelly Behan, Brigid Reynolds, Reisa A Sperling, Keith A Johnson, Gad Marshall, Marwan N Sabbagh, Sandra A Jacobson, Sherye A Sirrel, Thomas O Obisesan, Saba Wolday, Joanne Allard, Sterling C Johnson, J Jay Fruehling, Sandra Harding, Elaine R Peskind, Eric C Petrie, Gail Li, Jerome A Yesavage, Joy L Taylor, Ansgar J Furst, Steven Chao, Norman Relkin, Gloria Chaing, Lisa Ravdin

Affiliations

¹ Keenan Research Centre for Biomedical Science, The Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
² Faculty of Medicine, Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
³ Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
⁴ Department of Clinical Health Psychology, College of Medicine, Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
⁵ Hotchkiss Brain Institute, Calgary, AB, Canada.
⁶ Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
⁷ Division of Neurosurgery, Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
⁸ Division of Neurosurgery, St. Michael's Hospital, Toronto, ON, Canada.

Abstract

Objective: We conducted a neuroimaging analysis to understand the neuroanatomical correlates of gray matter loss in a group of mild cognitive impairment and early Alzheimer's disease patients who developed delusions.

Methods: With data collected as part of the Alzheimer's Disease Neuroimaging Initiative, we conducted voxel-based morphometry to determine areas of gray matter change in the same Alzheimer's Disease Neuroimaging Initiative participants, before and after they developed delusions.

Results: We identified 14 voxel clusters with significant gray matter decrease in patient scans post-delusional onset, correcting for multiple comparisons (false discovery rate, p < 0.05). Major areas of difference included the right and left insulae, left precuneus, the right and left cerebellar culmen, the left superior temporal gyrus, the right posterior cingulate, the right thalamus, and the left parahippocampal gyrus.

Conclusions: Although contrary to our initial predictions of enhanced right frontal atrophy, our preliminary work identifies several neuroanatomical areas, including the cerebellum and left posterior hemisphere, which may be involved in delusional development in these patients.

Keywords: Alzheimer's disease; delusions; psychosis; voxel-based morphometry.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / pathology*
Alzheimer Disease / psychology
Atrophy
Brain Mapping / methods
Cognitive Dysfunction / pathology*
Cognitive Dysfunction / psychology
Delusions / pathology*
Female
Gray Matter / pathology*
Humans
Image Processing, Computer-Assisted
Magnetic Resonance Imaging / methods
Male
Neuroimaging / methods

Abstract

Publication types

MeSH terms

Grants and funding