How does diabetes affect the risk of developing late-life mild cognitive impairment or dementia?
As we age, we worry about the incidence of mild cognitive impairment (MCI) and dementia. Unfortunately, dementia takes time to diagnose, and during this time it can progress quickly with poor outcomes. Previous studies have already determined an association between diabetes and dementia, predominantly in midlife patients. However, there is less evidence in older adults developing late-life incident MCI and who are progressing from MCI to dementia.
The current study used data from the prospective Atherosclerosis Risk in Communities (ARIC) Study to assess associations between late-life diabetes, glycemic control, diabetes duration and biomarkers of hyperglycemia with incident MCI and incident dementia. Due to the inclusion of complete cognitive measures, visit 5 in the ARIC was considered baseline for the current study and visit 6 was the follow-up after ~5 years. Of the 5,099 patients (ages 66-90), patients with diabetes were categorized by glycemic control and diabetes duration at baseline. Diabetes duration was calculated for each patient and either < 5 or > 5 years. Markers of glycemia were measured at visit 5, including HbA1c, fructosamine, glycated albumin, and 1,5-anhydroglucitol. Also, at baseline, cognitive status was categorized as either normal, MCI, or dementia. Incident cognitive impairment was defined as progression in cognitive status from baseline to follow-up; this could include either those normal at baseline returning with MCI or dementia, or someone with MCI at baseline returning with progressed dementia.
Baseline characteristics were displayed by means (SD). Cox proportional hazards models were used to analyze incident events. Results were both unadjusted and adjusted by potential confounders. Models were fit for four different cognitive outcomes listed as “incident dementia, incident MCI, incident cognitive impairment among all baseline participants, and incident dementia among those with MCI at baseline.” Restricted cubic splines with knots at different percentiles (5th, 35th, 65th, and 95th) were used to determine the association between the biomarkers of hyperglycemia and incident dementia. The biomarker values were converted to Z scores for comparison.
In patients cognitively normal at baseline, at follow-up 275 reported incident dementia and 455 with incident MCI. Diabetes was found to be significantly associated with incident MCI. However, this association was not found with incident dementia and differences due to glycemic control were found to not be significant. In terms of HbA1c, those with HbA1c > 7% were found to have a 1.73 times higher risk of developing MCI compared to patients without diabetes, whereas those with HbA1c < 7% were not found to be at a significantly higher risk. Comparing those with HbA1c > 7% and those with HbA1c < 7%, there was a 1.56 times greater risk for MCI in patients with HbA1c > 7%. Lastly, an association between a longer duration of diabetes was found with both incident dementia and incident MCI.
From baseline to follow-up, in patients with MCI, there was a significant association between diabetes and incident cognitive impairment, specifically seen in patients with HbA1c > 7%. In patients with diabetes > 5 years, they had 1.59 times the hazard of cognitive impairment versus patients with a shorter diabetes duration.
From the glycemic markers measured, a significant association was found between both high and low values of HbA1c and a higher risk of incident dementia. Also, there was a significant association between higher levels of fructosamine and glycated albumin and incident dementia, independent of HbA1c. This was not seen with 1,5-anhydroglucitol. As for the secondary analyses analyzing age and diabetes duration in patients with diabetes but without dementia, age was determined to be a strong driver for associations verses duration. Regardless of diabetes duration, patients older at baseline had a higher risk of incident dementia.
The authors concluded effects of diabetes, glycemic control, and diabetes duration can impact cognitive function, progressing from normal to MCI to dementia. Diabetes, poor glycemic control, and longer diabetes duration were all associated with worse cognitive outcomes. Patients with controlled glycemic levels didn’t show a significantly higher risk of cognitive impairment. However, lower HbA1c levels (< 5.8%) were associated with a higher risk of incident dementia. In the study, the patients who didn’t attend visit 6 were most of the dementia cases found. The authors reasoned those who were cognitively impaired would be more likely to drop out; however, telephone phone calls were able to collect data that would have otherwise not been included.
- Patients with diabetes, poor glycemic control, and longer diabetes duration were all associated with worse cognitive outcomes.
- As patients with diabetes age, it is increasingly important to maintain glycemic control to lessen cognitive impairments.
- Maintaining other risk factors for dementia with diet, exercise, and controlling vascular disease, can also help to decrease risk in patients with diabetes.
Rawlings, Andreea, et al. The Association of Late-Life Diabetes Status and Hyperglycemia With Incident Mild Cognitive Impairment and Dementia: The ARIC Study. Diabetes Care. 2019 May 21.
Emma Kammerer, L|E|C|O|M Bradenton School of Pharmacy, PharmD Candidate