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 C. 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 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; 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 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

doi:10.1212/WNL.0000000000006955

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 C. 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, 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 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 journal › Article › peer-review

71 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 language	English
Pages (from-to)	E823-E830
Journal	Neurology
Volume	92
Issue number	8
DOIs	https://doi.org/10.1212/WNL.0000000000006955
State	Published - Feb 19 2019

Bibliographical note

Funding Information:
C. Moran is a recipient of an NMRC-ARC Dementia Research Development Fellowship. R. Beare is a recipient of NHMRC project grants. W. Wang reports no disclosures relevant to the manuscript. M. Callisaya is a recipient of an Alzheimer’s Australia Research Foundation Grant & NHMRC Early Career Fellowship. V. Srikanth is a recipient of a National Health and Medical Research Council (NHMRC) Practitioner Fellowship and NHMRC project grants. Go to Neurology.org/N for full disclosures.

Funding Information:
Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (NIH grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through contributions from the following: AbbVie; Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the NIH (fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.

Publisher Copyright:
© 2019 American Academy of Neurology.

ASJC Scopus subject areas

Clinical Neurology

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This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1212/WNL.0000000000006955

Cite this

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. C., 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

@article{8838d773001541cd88a067774c59ba13,

title = "Type 2 diabetes mellitus, brain atrophy, and cognitive decline",

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.",

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

note = "Funding Information: C. Moran is a recipient of an NMRC-ARC Dementia Research Development Fellowship. R. Beare is a recipient of NHMRC project grants. W. Wang reports no disclosures relevant to the manuscript. M. Callisaya is a recipient of an Alzheimer{\textquoteright}s Australia Research Foundation Grant & NHMRC Early Career Fellowship. V. Srikanth is a recipient of a National Health and Medical Research Council (NHMRC) Practitioner Fellowship and NHMRC project grants. Go to Neurology.org/N for full disclosures. Funding Information: Data collection and sharing for this project was funded by the Alzheimer{\textquoteright}s Disease Neuroimaging Initiative (ADNI) (NIH grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through contributions from the following: AbbVie; Alzheimer{\textquoteright}s Association; Alzheimer{\textquoteright}s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the NIH (fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer{\textquoteright}s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Publisher Copyright: {\textcopyright} 2019 American Academy of Neurology.",

year = "2019",

month = feb,

day = "19",

doi = "10.1212/WNL.0000000000006955",

language = "English",

volume = "92",

pages = "E823--E830",

number = "8",

}

Moran, C, Beare, R, Wang, W, Callisaya, M, Srikanth, V, Weiner, M, Aisen, P, Petersen, R, Jack, CR, Jagust, W, Trojanowki, JQ, Toga, AW, Beckett, L, Green, RC, Saykin, AJ, Morris, JC, Liu, E, Montine, T, Gamst, A, Thomas, RG, Donohue, M, Walter, S, Gessert, D, Sather, T, Harvey, D, Kornak, J, Dale, A, Bernstein, M, Felmlee, J, Fox, N, Thompson, P, Schuff, N, Alexander, G, Decarli, C, Bandy, D, Koeppe, RA, Foster, N, Reiman, EM, Chen, K, Mathis, C, Cairns, NJ, Taylor-Reinwald, L, Trojanowki, JQ, Shaw, L, Lee, VMY, Korecka, M, Crawford, K, Neu, S, Foroud, TM, Potkin, S, Shen, L, Kachaturian, Z, Frank, R, Snyder, PJ, Molchan, S, Kaye, J, Quinn, J, Lind, B, Dolen, S, Schneider, LS, Pawluczyk, S, Spann, BM, Brewer, J, Vanderswag, H, Heidebrink, JL, Lord, JL, Johnson, K, Doody, RS, Villanueva-Meyer, J, Chowdhury, M, Stern, Y, Honig, LS, Bell, KL, Ances, B, Carroll, M, Leon, S, Mintun, MA, Schneider, S, Marson, D, Griffith, R, Clark, D, Grossman, H, Mitsis, E, Romirowsky, A, Detoledo-Morrell, L, Shah, RC, Duara, R, Varon, D, Roberts, P, Albert, M, Onyike, C, Kielb, S, Rusinek, H, De Leon, MJ, Glodzik, L, De Santi, S, Doraiswamy, PM, Petrella, JR, Coleman, RE, Arnold, SE, Karlawish, JH, Wolk, D, Smith, CD, Jicha, G, Hardy, P, Lopez, OL, Oakley, M, Simpson, DM, Porsteinsson, AP, Goldstein, BS, Martin, K, Makino, KM, Ismail, MS, Brand, C, Mulnard, RA, Thai, G, McAdams-Ortiz, C, Womack, K, Mathews, D, Quiceno, M, Diaz-Arrastia, R, King, R, Weiner, M, Martin-Cook, K, Devous, M, Levey, AI, Lah, JJ, Cellar, JS, Burns, JM, Anderson, HS, Swerdlow, RH, Apostolova, L, Lu, PH, Bartzokis, G, Silverman, DHS, Graff-Radford, NR, Parfitt, F, Johnson, H, Farlow, MR, Hake, AM, Matthews, BR, Herring, S, Van Dyck, CH, Carson, RE, Macavoy, MG, Chertkow, H, Bergman, H, Hosein, C, Black, S, Stefanovic, B, Caldwell, C, Robin Hsiung, GY, Feldman, H, Mudge, B, Assaly, M, Kertesz, A, Rogers, J, Trost, D, Bernick, C, Munic, D, Kerwin, D, Mesulam, MM, Lipowski, K, Wu, CK, Johnson, N, Sadowsky, C, Martinez, W, Villena, T, Turner, RS, Johnson, K, Reynolds, B, Sperling, RA, Johnson, KA, Marshall, G, Frey, M, Yesavage, J, Taylor, JL, Lane, B, Rosen, A, Tinklenberg, J, Sabbagh, M, Belden, C, Jacobson, S, Kowall, N, Killiany, R, Budson, AE, Norbash, A, Johnson, PL, Obisesan, TO, Wolday, S, Bwayo, SK, Lerner, A, Hudson, L, Ogrocki, P, Fletcher, E, Carmichael, O, Olichney, J, Kittur, S, Borrie, M, Bartha, DR, Johnson, S, Asthana, S, Carlsson, CM, Potkin, SG, Preda, A, Nguyen, D, Tariot, P, Fleisher, A, Reeder, S, Bates, V, Capote, H, Rainka, M, Scharre, DW, Kataki, M, Zimmerman, EA, Celmins, D, Brown, AD, Pearlson, GD, Blank, K, Anderson, K, Santulli, RB, Schwartz, ES, Sink, KM, Williamson, JD, Garg, P, Watkins, F, Ott, BR, Querfurth, H, Tremont, G, Salloway, S, Malloy, P, Correia, S, Rosen, HJ, Miller, BL, Mintzer, J, Longmire, CF, Spicer, K, Finger, E, Rachinsky, I, Drost, D, Pomara, N, Hernando, R, Sarrael, A, Schultz, SK, Boles Ponto, LL, Shim, H, Smith, KE, Relkin, N, Chaing, G, Raudin, L, Smith, A, Fargher, K & Raj, BA 2019, 'Type 2 diabetes mellitus, brain atrophy, and cognitive decline', Neurology, vol. 92, no. 8, pp. E823-E830. https://doi.org/10.1212/WNL.0000000000006955

TY - JOUR

T1 - Type 2 diabetes mellitus, brain atrophy, and cognitive decline

AU - Moran, Chris

AU - Beare, Richard

AU - Wang, Wei

AU - Callisaya, Michele

AU - Srikanth, Velandai

AU - Weiner, Michael

AU - Aisen, Paul

AU - Petersen, Ronald

AU - Jack, Clifford R.

AU - Jagust, William

AU - Trojanowki, John Q.

AU - Toga, Arthur W.

AU - Beckett, Laurel

AU - Green, Robert C.

AU - Saykin, Andrew J.

AU - Morris, John C.

AU - Liu, Enchi

AU - Montine, Tom

AU - Gamst, Anthony

AU - Thomas, Ronald G.

AU - Donohue, Michael

AU - Walter, Sarah

AU - Gessert, Devon

AU - Sather, Tamie

AU - Harvey, Danielle

AU - Kornak, John

AU - Dale, Anders

AU - Bernstein, Matthew

AU - Felmlee, Joel

AU - Fox, Nick

AU - Thompson, Paul

AU - Schuff, Norbert

AU - Alexander, Gene

AU - Decarli, Charles

AU - Bandy, Dan

AU - Koeppe, Robert A.

AU - Foster, Norm

AU - Reiman, Eric M.

AU - Chen, Kewei

AU - Mathis, Chet

AU - Cairns, Nigel J.

AU - Taylor-Reinwald, Lisa

AU - Trojanowki, J. Q.

AU - Shaw, Les

AU - Lee, Virginia M.Y.

AU - Korecka, Magdalena

AU - Crawford, Karen

AU - Neu, Scott

AU - Foroud, Tatiana M.

AU - Potkin, Steven

AU - Shen, Li

AU - Kachaturian, Zaven

AU - Frank, Richard

AU - Snyder, Peter J.

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N1 - Funding Information: C. Moran is a recipient of an NMRC-ARC Dementia Research Development Fellowship. R. Beare is a recipient of NHMRC project grants. W. Wang reports no disclosures relevant to the manuscript. M. Callisaya is a recipient of an Alzheimer’s Australia Research Foundation Grant & NHMRC Early Career Fellowship. V. Srikanth is a recipient of a National Health and Medical Research Council (NHMRC) Practitioner Fellowship and NHMRC project grants. Go to Neurology.org/N for full disclosures. Funding Information: Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (NIH grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through contributions from the following: AbbVie; Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the NIH (fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Publisher Copyright: © 2019 American Academy of Neurology.

PY - 2019/2/19

Y1 - 2019/2/19

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85061857085&partnerID=8YFLogxK

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U2 - 10.1212/WNL.0000000000006955

DO - 10.1212/WNL.0000000000006955

M3 - Article

C2 - 30674592

AN - SCOPUS:85061857085

VL - 92

SP - E823-E830

IS - 8

ER -

Type 2 diabetes mellitus, brain atrophy, and cognitive decline

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