Relationship between Executive Functioning and Glycemic Controls in Patients with Type 2 Diabetes

Type 2 diabetes (T2D) is a risk factor for Alzheimer’s disease. Executive dysfunction occurs in otherwise cognitively normal patients with T2D. To assess executive function, we investigated the relationship between executive function and glycemic controls using verbal fluency (VF) tests. The present study enrolled 130 patients with T2D (age, ≥60; including 11 patients with dementia) and excluded stroke survivors. Their HbA1c levels were recorded every ≤12 weeks for >5 years. All patients underwent VF tests. We analyzed the correlation between VF z-scores (standardized total scores) and glycemic control values (time-weighted average and maximum HbA1c levels for the past 5 years), or disease durations. As controls, we also investigated the relationships between stages of diabetic retinopathy (NDR/NPDR/PD) and past glycemic controls. The mean patient age was 74.7 years, the mean HbA1c at the baseline was 7.5%, median duration of education was 12 years, and mean disease duration was 18.3 years. Significant correlates for VF z-scores were age, years of education, and dementia in addition to glycemic control values. VF z-scores tended to correlate with average HbA1c levels, and significantly correlated with maximum HbA1c levels, for the past 5 years. The relationships between VF z-scores and maximum HbA1c levels remained significant after adjusting for age, years of education, and dementia. Generally, VF z-scores were strongly associated with maximum HbA1c levels for longer observation periods, i.e., VF z-scores correlated with maximum HbA1c levels for the past 5 years, best compared with maximum HbA1c levels for the past 4 years. As controls, diabetic retinopathy stages were also associated with average and maximum HbA1c levels. The diabetes duration was associated with diabetic retinopathy stages strongly, but not with VF z-scores. These results suggest that executive dysfunction may be caused by metabolic mechanisms other than diabetic retinopathy.