Glucose control and working memory as a function of age in older type 2 diabetics: Results from the Look AHEAD Ancillary Brain Study

Type 2 diabetes mellitus (T2DM) is becoming increasingly prevalent in the US, especially in older adults. In fact, 25.9% of adults over the age of 65 have been diagnosed with T2DM. In addition to the increased cardiovascular disease risks, cognitive and brain health impairments are also associated with T2DM. Overall lower brain volumes and poorer memory function is observed in T2DM, indicating poorer brain health than non-diabetics. While the mechanisms behind poorer cognitive function and brain health are unknown, impaired glucose control, as measured by glycated hemoglobin (HbA1c), is one aspect of T2DM that may provide insight into this ongoing inquiry. The Action for Health in Diabetes (Look AHEAD) trial was designed to longitudinally examine the cardiovascular health effects of weight-loss in older adults diagnosed with T2DM. The trial randomized participants into two conditions: Intensive Lifestyle Intervention (ILI) consisting of a physical activity regimen and caloric-restriction diet, and Diabetes Support and Education (DSE) control group offering seminars on diet, exercise, and diabetes symptoms management. At year 10 of the trial, participants (N = 237, mean age = 67 years) were recruited for a magnetic resonance imaging (MRI) ancillary study, in which participants completed a working memory task during a functional MRI (fMRI) scan and blood draw to measure HbA1c levels. Results indicate that age moderates the relationship between intervention group and cognitive function and the relationship between HbA1c and cognitive function, such that older adults in the ILI group, but not control group have the best glucose control yet worst performance. Further analyses reveal that the older adults in the ILI group with high HBA1c levels performed significantly better than those with lower HbA1c levels. Together, these results suggest that HbA1c is protective to working memory function in old age within T2DM. fMRI identifies regions in the prefrontal cortex, cingulate, insula, and hippcampus where HbA1c is associated with brain activity during the working memory task. However, no group differences in brain activity were identified. As T2DM becomes more prevalent in the population, it is critical to understand the cognitive impact this disease may have on patients, especially as they age