The Association of Late-Life Diabetes Status and Hyperglycemia With Incident Mild Cognitive Impairment and Dementia: The ARIC Study

Abstract

Objective: We sought to examine associations in older adults among diabetes, glycemic control, diabetes duration, and biomarkers of hyperglycemia with incident mild cognitive impairment (MCI) and incident dementia.

Research design and methods: We conducted a prospective analysis of 5,099 participants from the Atherosclerosis Risk in Communities (ARIC) Study who attended the fifth (2011-2013) exam. Cognitive status was assessed during follow-up via telephone calls, death certificate codes, surveillance, and a follow-up examination (2016-2017). We defined incident cognitive impairment as incident MCI or incident dementia in persons dementia-free at the index examination; we also examined each outcome separately. Diabetes was defined using self-report, medications, or HbA_1c ≥6.5%; poor glycemic control in persons with diabetes was defined as HbA_1c ≥7%. We examined the following biomarkers of hyperglycemia: HbA_1c, fructosamine, glycated albumin, and 1,5-anhydroglucitol.

Results: Mean age at baseline was 76 years, 59% were female, and 21% were black. Diabetes (hazard ratio [HR] 1.14 [95% CI 1.00, 1.31]), poor glycemic control in persons with diabetes (HR 1.31 [95% CI 1.05, 1.63]), and longer diabetes duration (≥5 vs. <5 years; HR 1.59 [95% CI 1.23, 2.07]) were significantly associated with incident cognitive impairment. We found a J-shaped association between HbA_1c and incident dementia. Glycated albumin and fructosamine were also associated with incident dementia, independently of HbA_1c. HbA_1c and fructosamine were also associated with incident MCI.

Conclusions: Diabetes status, poor glycemic control, and longer diabetes duration were associated with worse cognitive outcomes over a median follow-up of 5 years.

Figure 1

Adjusted HRs (95% CI) for standardized (actual) HbA_1c, 1,5-AG, GA, and fructosamine with incident dementia among persons dementia-free at baseline. Biomarker values are shown as Z scores (original units). HRs (solid line) and 95% CIs (dashed lines) are from Cox proportional hazard regression, adjusted for age, race, sex, education level, cigarette smoking status (current/former/never), drinking status (current/former/never), APOE e4 (zero, one, or two alleles), hypertension (yes/no), history of stroke (yes/no), and history of CHD (yes/no). Each biomarker was modeled using a restricted cubic spline, with knots at the 5th, 35th, 65th, and 95th percentiles, and centered at the median. Histograms of each biomarker are shown separately for persons without (solid bars) and with (outlined bars) diabetes.