Association of Glycemia, Lipids, and Blood Pressure With Cognitive Performance in People With Type 2 Diabetes in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE)
Authors: Luchsinger José A. , Younes Naji , Manly Jennifer J. , Barzilay Joshua , Valencia Willy , Larkin Mary E. , Falck-Ytter Corinna , Krause-Steinrauf Heidi , Pop-Busui Rodica , Florez Hermes , Seaquist Elizabeth ,   GRADE Research Group, Crandall Jill P. , McKee Melissa Diane , Brown-Friday Janet , Xhori Entila , Ballentine-Cargill Keisha , Duran Sally , Lukin Jennifer , Beringher Stephanie , Gonzalez de la torre Susana , Phillips Lawrence , Burgess Elizabeth , Olson Darin , Rhee Mary , Wilson Peter , Raines Tasha Stephanie , Costello Julie , Gullett Chona , Maher-Albertelli Maxine , Morehead Folayan , Mungara Radhika , Person Saranjit , Savoye Louise , Sibymon Mabil , Tanukonda Sridhar , White Carol Ann , Holloway Leah , Adams Cynthia , Ross April , Balasubramanyam Ashok , Gonzalez Erica , Wright Charlyne , Hollander Priscilla , Roe Erin , Uy Analyn , Burt Polly , Estrada Lorie , Chionh Kris , Ismail-Beigi Faramarz , Falck-Ytter Corinna , Sayyed Kassem Laure , Sood Ajay , Tiktin Margaret , Cramer Bethany , Iacoboni Jacalyn , Kononets Maria V. , Kulow Tanya , Newman Cynthia , Stancil Katherine A. , Sanders Cristina , Tucker Lisa , Werner Amanda , Krol Adrienne , McPhee Gloria , Patel Christine , Colosimo Linda , Goland Robin , Pring James , Kringas Patricia , Tejada Jessica , Hausheer Camille , Schneier Harvey , Gumpel Kelly , Kirpitch Amanda , Green Jennifer B. , AbouAssi Hiba , Chatterjee Ranee , Feinglos Mark N. , English Jones Jennifer , Khan Shubi A. , Kimpel Jeanne B. , Zimmer Ronna P. , Furst Mary , Satterwhite Barbara M. , Thacker Connie R. , Evans Kreider Kathryn , Mather Kieren J. , Lteif Amale , Hamilton Tonya , Patel Nick , Riera Gabriela , Jackson Marcia , Pirics Vivian , Howard Devin , Aguillar Danielle , Hurt Sloan , Bergenstal Richard , Carlson Anders , Martens Thomas , Johnson Mary , Hill Renae , Hyatt Jamie , Jensen Connie , Madden Marcia , Martin Dianna , Willis Holly , Konerza Wanda , Passi Rebecca , Kleeberger Kathleen , Fortmann Stephen , Herson Michael , Mularski Karen , Glauber Harry , Prihoda James , Ash Britt , Carlson Christina , Ramey Phyllis Anne , Schield Emily , Torgrimson-Ojerio Britta , Arnold Kathy , Kauffman Bryan , Panos Elease , Sahnow Samantha , Bays Kristi , Cook Jennifer , Gluth Jennifer , Sasaki Debra , Schell Katrina , Criscola Jennifer , Friason Camille , Jones Suzi , Nazarov Sergey , Barzilay Joshua , Rassouli Negah , Puttnam Rachel , Curtis Michelle , Stokes Kia , Hollis Bonita , Sanders-Jones Cynthia , Nelson Roslin , El-Haqq Zakiah , Kolli Abby , Tran Tu , Wexler Deborah , Larkin Mary , Meigs James , Dushkin Amy , Rocchio Gianna , Chambers Brittany , Yepes Mike , Steiner Barbara , Dulin Hilary , Cayford Melody , DeManbey Andrea , Gurry Lindsey , Hillard Mallory , Martin Kimberly , Stevens Christine , Thangthaeng Nopporn , Kochis Raquel , Raymond Elyse , Ripley Valerie , Park Jean , Aroda Vanita , Ghazi Adline , Loveland Amy , Hurtado Maria , Kuhn Alexander , Mofor Florence , Florez Hermes J. , Valencia Willy Marcos , Marks Jennifer , Oropesa-Gonzalez Lisset , Riccio Veliz Ana K. , Nieto-Martinez Ramfis , Gutt Miriam , Ahmann Andrew , Aby-Daniel Diana , Joarder Farahnaz , Morimoto Victoria , Sprague Carol , Yamashita Daisuke , Cady Nancy , Kirchhoff Patricia , Rivera- Eschright Nadia , Adducci Joseph , Morales Gomez Brianna , Goncharova Alina , Hox Sophia H. , Petrovitch Helen , Matwichyna Michael , Jenkins Victoria , Bermudez Nina O. , Ishii Renée R. , Hsia Daniel S. , Cefalu William T. , Greenway Frank L. , Waguespack Celeste , King Erin , Haynes Natalie , Thomassie Amy , Bourgeois Brandi , Hazlett Claire , Henry Robert , Mudaliar Sunder , Boeder Schafer , Pettus Jeremy , Diaz Elsa , DeLue Catherine , Castro Erick , Hernandez Sylvia , Krakoff Jonathan , Curtis Jeffrey M. , Killean Tina , Joshevama Erica , Diaz Enrique , Martin Denelle , Karshner Tracey , Albu Jeanine , Pi-Sunyer F. Xavier , Frances Sylvaine , Maggio Carol , Ellis Emily , Bastawrose Joseph , Gong Xiuqun , Banerji Mary Ann , August Phyllis , Lorber Daniel , Brown Necole M. , Josephson Debra H. , Thomas Lorraine L. , Tsovian Mari , Cherian Ajini , Jacobson Marlo H. , Mishko Motria M. , Kirkman M. Sue , Bergamo Katherine , Buse John B. , Dostou Jean , Young Laura , Goley April , Kerr Jeffrey , Largay Joseph F. , Guarda Sonia , Cuffee Juanita , Culmer Dawn , Fraser Rachael , Almeida Hope , Coffer Samantha , Debnam Elizabeth , Kiker Lauren , Morton Sarah , Josey Kim , Fuller Gail , Garvey W. Timothy , Cherrington Andrea , Golson Dana , Griffith Olivia , Robertson Mary Catherine , Agne April , McCullars Steve , Cohen Robert M. , Craig Jacqueline , Kersey Kimberly , Rogge M. Colleen , Wilson Carla , Burton Kathryn , Lipp Sonia , Vonder Meulen Mary Beth , Rasouli Neda , Schroeder Emily , Steiner Stephanie , Baker Chelsea , Underkofler Chantal , Douglass Sara , Sivitz William , Cline Erin , Knosp Laura , McConnell Jennifer , Lowe Tamara , Herman William H. , Pop-Busui Rodica , Tan Meng H. , Martin Catherine , Waltje Andrea , Goodhall Lynn , Eggleston Rebecca , Kuo Shihchen , Bule Stephanie , Kessler Nancy , LaSalle Elizabeth , Seaquist Elizabeth R. , Bantle Anne , Kumar Anjali , Redmon Bruce , Bantle John , Harindhanavudhi Tasma , Coe Mary , Mech Michael , Taddese Abdisa , Lesne Lesia , Smith Shannon , Desouza Cyrus , Kuechenmeister Lisa , Shivaswamy Vijay , Morales Ana Laura , Rodriguez Maria Grace , Seipel Kris , Alfred Alissa , Eggert Jenna , Lord Grace , Taylor William , Tillson Renee , Schade David S. , Adolphe Allen , Burge Mark , Duran-Valdez Elizabeth , Martinez Janae , Hernandez McGinnis Doris , Pucchetti Benjamin , Scripsick Elizabeth , DeFronzo Ralph A. , Cersosimo Eugenio , Abdul-Ghani Muhammad , Triplitt Curtis , Verastiqui Hector , Garza Rosa Irene , Wright Kathryn , Puckett Curtiss , Raskin Philip , Rhee Chanhaeng , Abraham Soma , Jordan Lin Fan , Sao Serey , Morton Luisa , Smith Oralenda , Osornio Walker Laura , Schnurr-Breen Laura , Ayala Rosa , Kraymer Robert Brian , Sturgess Daytheon , Utzschneider Kristina M. , Kahn Steven E. , Alarcon-Casas Wright Lorena , Boyko Edward J. , Tsai Elaine C. , Trence Dace L. , Fattaleh Basma N. , Montgomery Brenda K. , Atkinson Karen M. , Concepcion Tessa , Kozedub Alexandra , Moak Cameron , Rhothisen Samantha , Elasy Tom A. , Martin Stephanie , Shackelford Laura , Goidel Rita , Hinkle Nina , Lipps Hogan Janie , Lovell Cynthia , Myers Janet , McGill Janet B. , Salam Maamoun , Kissel Sarah , Schweiger Toni , Recklein Carol Tamborlane William , Gatcomb Patricia , Camp Anne , Gulanski Barbara , Inzucchi Silvio , Pham Kim , Alguard Michele , Lessard Katarzyna , Perez Magalys , Magenheimer Elizabeth , Montoza Abmaridel , Nathan David M. , Lachin John , Buse John B. , Kahn Steven E. , Krause-Steinrauf Heidi , Larkin Mary , Tiktin Margaret , Wexler Deborah , Burch Henry B. , Linder Barbara , Bremer Andrew , Younes Naji , Backman Michael , Bebu Ionut , Buys CJ , Fagan Murphy Anna , Gao Yuping , Gramzinski Michaela , Hall Stephanie , Legowski Elizabeth , Arey Alyssa , Bethepu Joel , Lund Claire , Mangat Dhaliwal Pam , McGee Paula , Mesimer Emily , Ngo Lisa , Steffes Michael , Seegmiller Jesse , Saenger Amy , Arends Valerie , Gabrielson Deanna , Conner Todd , Warren Stuart , Day Jolene , Scrymgeour Alexandra , Soliman Elsayed Z. , Zhang Zhu-Ming , Campbell Charles , Hu Julie , Keasler Lisa , Hensley Susan , Li Yabing , Herman William , Martin Catherine , Waltje Andrea , Kuo Shihchen , Mihalcea Rada , Perez-Rosas Veronica , Prosser Lisa , Resnicow Kenneth , Ye Wen , Shao Hui , Zhang Ping , Luchsinger Jose , Sanchez Danurys , Burch Henry B. , Bremer Andrew , Linder Barbara , Fradkin Judith , Groessl Erik , Chong Helen , Hillery Naomi , Abdouch Ivan , Brantley Paula , Broyles Frances E. , Canaris Gay , Copeland Paul , Craine Jeri J. , Fein Warren L. , Lee Melissa S. , Meiners Rebecca , Meiners Vaughn , O’Neal Hollis , Park James E. , Sledge Edward , Steppel-Resnick Jeanne , Turchin Alexander , Brooks-Worrell Barbara , Hampe Christiane S. , Newgard Christopher B. , Palmer Jerry P. , Shojaie Ali , Higgins John , Fischer Lawrence , Golden Sherita , Gonzalez Jeffery , Naik Aanand , Walker Elizabeth , Doner Lotenberg Lynne , Gallivan Joanne , Lim Joanne , Tuncer Diane M. , Behringer-Massera Stephanie 
Published: July 2021

OBJECTIVE
Type 2 diabetes is a risk factor for cognitive impairment. We examined the relation of glycemia, lipids, blood pressure (BP), hypertension history, and statin use with cognition in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).

RESEARCH DESIGN AND METHODS
Cross-sectional analyses from GRADE at baseline examined the association of glycemia (hemoglobin A1c [HbA1c]), LDL, systolic BP (SBP) and diastolic BP (DBP), hypertension history, and statin use with cognition assessed by the Spanish English Verbal Learning Test, letter and animal fluency tests, and Digit Symbol Substitution Test (DSST).

RESULTS
Among 5,047 GRADE participants, 5,018 (99.4%) completed cognitive assessments. Their mean age was 56.7 ± 10.0 years, and 36.4% were women. Mean diabetes duration was 4.0 ± 2.7 years. HbA1c was not related to cognition. Higher LDL was related to modestly worse DSST scores, whereas statin use was related to modestly better DSST scores. SBP between 120 and 139 mmHg and DBP between 80 and 89 mmHg were related to modestly better DSST scores. Hypertension history was not related to cognition.

CONCLUSIONS
In people with type 2 diabetes of a mean duration of &lt;5 years, lower LDL and statin use were related to modestly better executive cognitive function. SBP levels in the range of 120–139 mmHg and DBP levels in the range of 80–89 mmHg, but not lower levels, were related to modestly better executive function. These differences may not be clinically significant.