AUTHOR=Zimering Mark B. , Knight Jeffrey , Ge Ling , Bahn Gideon , the VADT Investigators , Soule Jeremy , Caulder Susan , Pittman Clare , Alston Omayra , Mayfield Ronald K. , Moffitt Greg , Sagel Julius , Sanacor Frank , Ganaway Elizabeth , Marks Jennifer , Okur Lorraine , Jones Lucille , Florez Hermes , Pfeifer Donna , Samos Luis , Taylor Andrew L. , Zimering Mark B. , Sama Adilia , Rosenberg Frances , Garcia Heidi , Ertel Norman , Pogach Leonard , John J. Shin , Caldarella Felice , Carseli Constantino , Shah Mamta , Ginier Paulette , Arakel George , Fu Yangheng , Tayloe Don , Allen Jack E. , Fox Elizabeth , Hensley Paula G. , Emanuele Nicholas , Kahsen Kathleen , Linnerud Patricia , Agrawal Lily , Azad Nasrin , Marcelli Marco , Cunningham Glenn R. , Nichols Natalie M. , Cordero Emilia , Hijazi Rabih , Roman Farid , Datta Paromita , Garcia Touza Mariana , Lteif Amale , Moore Karen L. , Lazar-Robinson Christina , Gupta Sanjay , Kirkman M. Sue , Mendez Martha , Haider Zehra , Risley Lora , Karounos Dennis , Barber Linda , Hibbard Janet , Anderson James W. , Reynolds L. Raymond , Carlsen Jeff , Collins Robert W. , Ehtisham As’ad , Kashyap Moti L. , Matheus Barbara , Rahbarnia Tina , Vo Anthony N. , Downey Nancy , Fox Lynette , Gonzales Richard M. , Meyers C. Daniel , Tavintharan Subramaniam , Nuttall Frank Q. , Cupersmith Lisa , Dardick Kathy , Kollman Linda , Georgopoulos Angeliki , Niewoehner Catherine , Davis Stephen N. , Harper Paula , Davis Diana , Devin Jessica , Marney Annis , Passyn-Dunn Julia , Perkins Jennifer , Stafford John , Powers Al , Balch Linda , Harris Patricia , Anderson Robert J. , Dunning Diana , Ludwig Steve , Vogel Marlene , DeSouza Cyrus , Ecklund Robert , Doran Sarah , Korolchuk Claire , McElmeel Mary , Wagstaff Sarah , Reaven Peter , Solie Bradley , Matchette John , Meyer Christian , Vela Sylvia , Aslam Nadeem , Brinton Eliot , Clark Joy , Domb Alisa , McDonald Linda , Shurtz Lynae , Rao R. Harsha , Beattie Janice N. , Franko Carol , DeRubertis Frederick R. , Kelly David , Maser Melisse , Paul Juleen , Zieve Franklin , Clark Susan J. , Grimsdale Ann , Fredrickson Sonja , Levy James , Schroeder Diane , Iranmanesh Ali , Dunn Barbara , Arsura Donna , Kovesdy Csaba , Hanna Suzanne , Iranmanesh Ashraf , Florow Christy , Remandaban Fe , Smith Erica , Henry Robert R. , Keller Miriam , Aroda Vanita , Choe Charles , Edelman Steven , Gasper Andrea , MaFong Dereck , Mudaliar Sunder , Oh Deborah , Bandukwala Rahil , Chang Anna , Chaudhary Sandeep , Chinnapongse Sithophol , Christiansen Louie , Chu Neelima , Kim Dennis , Lupo Mark , Chandra Manju , Plodkowski Ray , Sathyaprakash Roopa , Wilson Janet , Yu Joseph , Macaraeg Gina , Townes Shelley , DeFronzo Ralph , Johnson Lisa , Cusi Ken , Tripathy Devjit , Bajaj Mandeep , Blodgett Janet , Kayshup Sangeeta , Vasquez Mary Helen , Walz Barbara , Weaver Tess , Benabe Julio , Mercado Zuleika , Padilla Brunilda , Serrano-Rodriguez Jocelyn , Rosado Carlos , Mejias Edwin , Tejera Tania , Geldrez Clorinda , Gonzalez-Melendez Elda , Natal Maria , Rios Jimenez Maribel , Shah Jayendra H. , Wendel Wendy S. , Scott Lynnette , Gurnsey Lynne A. , Kwiecinski Fabia A. , Boyden Thomas , Goldschmidt Merilyn G. , Easton Virginia TITLE=Predictors of Cognitive Decline in Older Adult Type 2 Diabetes from the Veterans Affairs Diabetes Trial JOURNAL=Frontiers in Endocrinology VOLUME=7 YEAR=2016 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2016.00123 DOI=10.3389/fendo.2016.00123 ISSN=1664-2392 ABSTRACT=Aims

Cognitive decline disproportionately affects older adult type 2 diabetes. We tested whether randomized intensive (INT) glucose-lowering reduces the rate(s) of cognitive decline in adults with advanced type 2 diabetes (mean: age, 60 years; diabetes duration, 11 years) from the Veterans Affairs Diabetes Trial.

Methods

A battery of neuropsychological tests [digit span, digit symbol substitution (DSym), and Trails-making Test-Part B (TMT-B)] was administered at baseline in ~1700 participants and repeated at year 5. Thirty-seven risk factors were evaluated as predictors of cognitive decline in multivariable regression analyses.

Results

The mean age-adjusted DSym or TMT-B declined significantly in all study participants (P < 0.001). Randomized INT glucose-lowering did not significantly alter the rate of cognitive decline. The final model of risk factors associated with 5-year decline in age-adjusted TMT-B included as significant predictors: longer baseline diabetes duration (beta = −0.028; P = 0.0057), lower baseline diastolic blood pressure (BP; beta = 0.028; P = 0.002), and baseline calcium channel blocker medication use (beta = −0.639; P < 0.001). Higher baseline pulse pressure was significantly associated with decline in age-adjusted TMT-B suggesting a role for both higher systolic and lower diastolic BPs. Baseline thiazide diuretic use (beta = −0.549; P = 0.015) was an additional significant predictor of 5-year decline in age-adjusted digit symbol score. Post-baseline systolic BP-lowering was significantly associated (P < 0.001) with decline in TMT-B performance. There was a significant inverse association between post-baseline plasma triglyceride-lowering (P = 0.045) and decline in digit symbol substitution task performance.

Conclusion

A 5-year period of randomized INT glucose-lowering did not significantly reduce the rate of cognitive decline in older-aged adults with type 2 diabetes. Systolic and diastolic BPs as well as plasma triglycerides appeared as modifiable risk factors of the rate of cognitive decline in older adult type 2 diabetes.