Diabetes in midlife and cognitive change over 20 years: a cohort study

Abstract

Background: Type 2 diabetes is associated with dementia risk, but evidence is limited for possible associations of diabetes and prediabetes with cognitive decline.

Objective: To determine whether diabetes in midlife is associated with 20-year cognitive decline and to characterize long-term cognitive decline across clinical categories of hemoglobin A1c (HbA1c) levels.

Design: Prospective cohort study.

Setting: The community-based ARIC (Atherosclerosis Risk in Communities) study.

Participants: 13,351 black and white adults aged 48 to 67 years at baseline (1990 to 1992).

Measurements: Diabetes was defined by self-reported physician diagnosis or medication use or HbA1c level of 6.5% or greater. Undiagnosed diabetes, prediabetes, and glucose control in persons with diagnosed diabetes were defined by clinical categories of HbA1c level. Delayed word recall, digit symbol substitution, and word fluency tests were used to assess cognitive performance and were summarized with a global Z score.

Results: Diabetes in midlife was associated with a 19% greater cognitive decline over 20 years (adjusted global Z-score difference, -0.15 [;95% CI, -0.22 to -0.08];) compared with no diabetes. Cognitive decline was significantly greater among persons with prediabetes (HbA1c level of 5.7% to 6.4%) than among those with an HbA1c level less than 5.7%. Participants with poorly controlled diabetes (HbA1c level ≥ 7.0%) had greater decline than those whose diabetes was controlled (adjusted global Z-score difference, -0.16; P = 0.071). Longer-duration diabetes was also associated with greater late-life cognitive decline (P for trend < 0.001). Rates of decline did not differ significantly between white and black persons (P for interaction = 0.44).

Limitation: Single HbA1c measurement at baseline, 1 test per cognitive domain, and potential geographic confounding of race comparisons.

Conclusion: Diabetes prevention and glucose control in midlife may protect against late-life cognitive decline.

Primary funding source: National Institutes of Health.

Figure 1

Difference in global cognitive Z score decline by clinical categories of hemoglobin A1c compared to decline in persons without diabetes with hemoglobin A1c < 5.7%. Legend: Adjusted for attrition refers to the inverse probability of attrition weighting used to account for participant death or dropout during follow-up. Estimates (95% confidence intervals) are from generalized linear models fit using generalized estimating equations for global cognitive Z score, with adjustment for age, age-squared, race-center, sex, education, cigarette smoking status, drinking status, hypertension, history of coronary heart disease, history of stroke, APOE ε4 genotype, body mass index, interactions between these variables and time (except for drinking status and history of coronary heart disease, which were not significant), and interactions between race-center and sex, hypertension, and education. Hemoglobin A1c was categorized using the standard clinical cut-points based on American Diabetes Association criteria (in participants without a diagnosis of diabetes (N=12,107): <5.7% (N=9,031), 5.7-6.4% (N=2,365), and ≥6.5% (N=711); in participants with diagnosed diabetes(N=1,244): <7% (N=415), ≥7% (N=829).