Type 2 diabetes mellitus, brain atrophy, and cognitive decline

Chris Moran, Richard Beare, Wei Wang, Michele Callisaya, Velandai Srikanth, 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. ThomasMichael 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 Kachaturian, 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, Susan De Santi, P. Murali Doraiswamy, Jeffrey R. Petrella, R. Edward 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 McAdams-Ortiz, Kyle Womack, Dana Mathews, Mary Quiceno, Ramon Diaz-Arrastia, Richard King, Myron Weiner, 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 R. Farlow, Ann Marie Hake, Brandy R. Matthews, Scott Herring, 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, Benita Mudge, Michele Assaly, Andrew Kertesz, John Rogers, Dick Trost, Charles Bernick, Donna Munic, Diana Kerwin, Marek Marsel Mesulam, Kristina 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, Jerome Yesavage, Joy L. Taylor, Barton Lane, 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 T Carmichael, John Olichney, Smita Kittur, Michael Borrie, Dr 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, 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, Kenneth Spicer, Elizabether Finger, Irina Rachinsky, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Laura L. Boles Ponto, Hyungsub Shim, Karen Elizabeth Smith, Norman Relkin, Gloria Chaing, Lisa Raudin, Amanda Smith, Kristin Fargher, Balebail Ashok Raj

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)E823-E830
JournalNeurology
Volume92
Issue number8
DOIs
StatePublished - Feb 19 2019

ASJC Scopus subject areas

  • Clinical Neurology

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    Moran, C., Beare, R., Wang, W., Callisaya, M., Srikanth, V., Weiner, M., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Liu, E., Montine, T., Gamst, A., ... Raj, B. A. (2019). Type 2 diabetes mellitus, brain atrophy, and cognitive decline. Neurology, 92(8), E823-E830. https://doi.org/10.1212/WNL.0000000000006955