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 | |
State | Published - 19 Feb 2019 |
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In: Neurology, Vol. 92, No. 8, 19.02.2019, p. E823-E830.
Research output: Contribution to journal › Article › peer-review
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.
AU - Molchan, Susan
AU - Kaye, Jeffrey
AU - Quinn, Joseph
AU - Lind, Betty
AU - Dolen, Sara
AU - Schneider, Lon S.
AU - Pawluczyk, Sonia
AU - Spann, Bryan M.
AU - Brewer, James
AU - Vanderswag, Helen
AU - Heidebrink, Judith L.
AU - Lord, Joanne L.
AU - Johnson, Kris
AU - Doody, Rachelle S.
AU - Villanueva-Meyer, Javier
AU - Chowdhury, Munir
AU - Stern, Yaakov
AU - Honig, Lawrence S.
AU - Bell, Karen L.
AU - Ances, Beau
AU - Carroll, Maria
AU - Leon, Sue
AU - Mintun, Mark A.
AU - Schneider, Stacy
AU - Marson, Daniel
AU - Griffith, Randall
AU - Clark, David
AU - Grossman, Hillel
AU - Mitsis, Effie
AU - Romirowsky, Aliza
AU - Detoledo-Morrell, Leyla
AU - Shah, Raj C.
AU - Duara, Ranjan
AU - Varon, Daniel
AU - Roberts, Peggy
AU - Albert, Marilyn
AU - Onyike, Chiadi
AU - Kielb, Stephanie
AU - Rusinek, Henry
AU - De Leon, Mony J.
AU - Glodzik, Lidia
AU - De Santi, Susan
AU - Doraiswamy, P. Murali
AU - Petrella, Jeffrey R.
AU - Coleman, R. Edward
AU - Arnold, Steven E.
AU - Karlawish, Jason H.
AU - Wolk, David
AU - Smith, Charles D.
AU - Jicha, Greg
AU - Hardy, Peter
AU - Lopez, Oscar L.
AU - Oakley, Maryann
AU - Simpson, Donna M.
AU - Porsteinsson, Anton P.
AU - Goldstein, Bonnie S.
AU - Martin, Kim
AU - Makino, Kelly M.
AU - Ismail, M. Saleem
AU - Brand, Connie
AU - Mulnard, Ruth A.
AU - Thai, Gaby
AU - McAdams-Ortiz, Catherine
AU - Womack, Kyle
AU - Mathews, Dana
AU - Quiceno, Mary
AU - Diaz-Arrastia, Ramon
AU - King, Richard
AU - Weiner, Myron
AU - Martin-Cook, Kristen
AU - Devous, Michael
AU - Levey, Allan I.
AU - Lah, James J.
AU - Cellar, Janet S.
AU - Burns, Jeffrey M.
AU - Anderson, Heather S.
AU - Swerdlow, Russell H.
AU - Apostolova, Liana
AU - Lu, Po H.
AU - Bartzokis, George
AU - Silverman, Daniel H.S.
AU - Graff-Radford, Neill R.
AU - Parfitt, Francine
AU - Johnson, Heather
AU - Farlow, Martin R.
AU - Hake, Ann Marie
AU - Matthews, Brandy R.
AU - Herring, Scott
AU - Van Dyck, Christopher H.
AU - Carson, Richard E.
AU - Macavoy, Martha G.
AU - Chertkow, Howard
AU - Bergman, Howard
AU - Hosein, Chris
AU - Black, Sandra
AU - Stefanovic, Bojana
AU - Caldwell, Curtis
AU - Robin Hsiung, Ging Yuek
AU - Feldman, Howard
AU - Mudge, Benita
AU - Assaly, Michele
AU - Kertesz, Andrew
AU - Rogers, John
AU - Trost, Dick
AU - Bernick, Charles
AU - Munic, Donna
AU - Kerwin, Diana
AU - Mesulam, Marek Marsel
AU - Lipowski, Kristina
AU - Wu, Chuang Kuo
AU - Johnson, Nancy
AU - Sadowsky, Carl
AU - Martinez, Walter
AU - Villena, Teresa
AU - Turner, Raymond Scott
AU - Johnson, Kathleen
AU - Reynolds, Brigid
AU - Sperling, Reisa A.
AU - Johnson, Keith A.
AU - Marshall, Gad
AU - Frey, Meghan
AU - Yesavage, Jerome
AU - Taylor, Joy L.
AU - Lane, Barton
AU - Rosen, Allyson
AU - Tinklenberg, Jared
AU - Sabbagh, Marwan
AU - Belden, Christine
AU - Jacobson, Sandra
AU - Kowall, Neil
AU - Killiany, Ronald
AU - Budson, Andrew E.
AU - Norbash, Alexander
AU - Johnson, Patricia Lynn
AU - Obisesan, Thomas O.
AU - Wolday, Saba
AU - Bwayo, Salome K.
AU - Lerner, Alan
AU - Hudson, Leon
AU - Ogrocki, Paula
AU - Fletcher, Evan
AU - Carmichael, Owen
AU - Olichney, John
AU - Kittur, Smita
AU - Borrie, Michael
AU - Bartha, Dr Rob
AU - Johnson, Sterling
AU - Asthana, Sanjay
AU - Carlsson, Cynthia M.
AU - Potkin, Steven G.
AU - Preda, Adrian
AU - Nguyen, Dana
AU - Tariot, Pierre
AU - Fleisher, Adam
AU - Reeder, Stephanie
AU - Bates, Vernice
AU - Capote, Horacio
AU - Rainka, Michelle
AU - Scharre, Douglas W.
AU - Kataki, Maria
AU - Zimmerman, Earl A.
AU - Celmins, Dzintra
AU - Brown, Alice D.
AU - Pearlson, Godfrey D.
AU - Blank, Karen
AU - Anderson, Karen
AU - Santulli, Robert B.
AU - Schwartz, Eben S.
AU - Sink, Kaycee M.
AU - Williamson, Jeff D.
AU - Garg, Pradeep
AU - Watkins, Franklin
AU - Ott, Brian R.
AU - Querfurth, Henry
AU - Tremont, Geoffrey
AU - Salloway, Stephen
AU - Malloy, Paul
AU - Correia, Stephen
AU - Rosen, Howard J.
AU - Miller, Bruce L.
AU - Mintzer, Jacobo
AU - Longmire, Crystal Flynn
AU - Spicer, Kenneth
AU - Finger, Elizabether
AU - Rachinsky, Irina
AU - Drost, Dick
AU - Pomara, Nunzio
AU - Hernando, Raymundo
AU - Sarrael, Antero
AU - Schultz, Susan K.
AU - Boles Ponto, Laura L.
AU - Shim, Hyungsub
AU - Smith, Karen Elizabeth
AU - Relkin, Norman
AU - Chaing, Gloria
AU - Raudin, Lisa
AU - Smith, Amanda
AU - Fargher, Kristin
AU - Raj, Balebail Ashok
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
U2 - 10.1212/WNL.0000000000006955
DO - 10.1212/WNL.0000000000006955
M3 - Article
C2 - 30674592
AN - SCOPUS:85061857085
SN - 0028-3878
VL - 92
SP - E823-E830
JO - Neurology
JF - Neurology
IS - 8
ER -