Introduction & Objective: Alzheimer’s Disease and related dementias (ADRD) are more common in individuals with diabetes. Traditional glycemic measures such as average hemoglobin A1c (A1c) may not capture a dynamic and complex pathophysiology in the relationship between diabetes and ADRD. We developed a measure of glycemic control, A1c time-in-range (TIR), that expresses A1c stability over time within specific ranges and may inform our understanding of the relationship between glucose levels over time and ADRD incidence. The aim of this study is to examine the relationship between A1c TIR and incidence of ADRD in older Veterans with diabetes mellitus.
Methods: 374,021 Veterans aged 65 years or older with diabetes during the study period January 1, 2005 to December 31, 2018 were included in this cohort analysis. Individuals with fewer than four A1c tests during a 3-year baseline period (2005-2017), dementia at baseline, or less than 4 years of follow up were excluded. A1c TIR was calculated as the percentage of days during baseline in which A1c was in individualized target ranges based on clinical characteristics and predicted life expectancy, with higher A1c TIR viewed as more favorable.
Results: Adjusted Cox proportional hazards models showed that lower A1c TIR was associated with increased risk of incident ADRD (A1c TIR: 0-<20% [HR=1.19;95% CI, 1.16-1.23]). Further, below range A1c levels was associated with incident ADRD. Having greater time below range (A1c TBR) (≥60%) was associated with significantly increased risk (HR 1.23; 95% CI, 1.19-1.27). Findings remained significant after excluding individuals with baseline use of medications associated with hypoglycemia risk (i.e., insulin, sulfonylureas) or with hypoglycemia events.
Conclusion: Among older adults with diabetes, increasing A1c stability within patient-specific target ranges is associated with a lower risk of ADRD. A1c time below range may identify patients at increased risk of ADRD.
P.C. Underwood: None. L. Zhang: None. D. Mohr: None. J.C. Prentice: None. A.E. Budson: Advisory Panel; Eli Lilly and Company. Research Support; Bristol-Myers Squibb Company. Advisory Panel; AbbVie Inc. Research Support; VoxNeuro. Other Relationship; Elsevier, Oxford University Press. P.R. Conlin: None.
This study was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development (IIR 15-116) and the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK114098). Data were obtained with support from VA Information Resource Center, VA/CMS Data for Research Projects SDR 02-23 and 98-004.
