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High Hemoglobin A1c and Diabetes Predict Memory Decline in the Health and Retirement Study

Marden, Jessica R. ScD; Mayeda, Elizabeth R. PhD; Tchetgen Tchetgen, Eric J. PhD; Kawachi, Ichiro MD, PhD; Glymour, M. Maria ScD

Alzheimer Disease & Associated Disorders: January-March 2017 - Volume 31 - Issue 1 - p 48–54
doi: 10.1097/WAD.0000000000000182
Original Articles

Background: Type 2 diabetes (T2D) is an established risk factor for dementia, but evidence for T2D and memory decline is less consistent. Understanding how T2D and blood glucose relate to memory decline is crucial to elucidating the mechanisms linking T2D and dementia.

Materials and Methods: For 8888 Health and Retirement Study participants aged 50+, glycosylated hemoglobin (HbA1c) was measured in either 2006 or 2008 and physician’s diagnosis of diabetes was self-reported in the same year. Composite memory (z scored) was assessed biennially through 2012 using immediate and delayed word list recall or the Informant Questionnaire for Cognitive Decline. Marginal mean regression models for repeated outcomes were specified to predict memory decline as a function of diabetes or HbA1c, using age as the timescale and adjusting for health and social confounders.

Results: Diabetes was associated with a 10% faster rate of memory decline [β=−0.04 per decade; 95% confidence interval (CI), −0.06 to −0.01). A 1 U increase in HbA1c corresponded with a 0.05 SD decrease in memory score per decade (95% CI, −0.08 to −0.03). Even among individuals with HbA1c<6.5% (threshold for diabetes), higher HbA1c was associated with memory decline (β=−0.05 per decade; 95% CI, −0.08 to −0.03).

Discussion: Diabetes accelerated memory loss and higher HbA1c predicted memory decline even in nondiabetics.

*Departments of Social and Behavioral Sciences


§Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA

Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA

J.R.M. and E.J.T.T. received support from National Institute of Allergy and Infectious Diseases, grant # NIAID R01 AI104459.

The authors declare no conflicts of interest.

Reprints: Jessica R. Marden, ScD, Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Kresge Building, Boston, MA 02115 (e-mail:

Received May 12, 2016

Accepted November 4, 2016

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved