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Abstract and Introduction
Abstract
Patients with type 2 diabetes demonstrate reduced functional connectivity within the resting state default mode network (DMN), which may signal heightened risk for cognitive decline. In other populations at risk for cognitive decline, additional magnetic resonance imaging abnormalities are evident during task performance, including impaired deactivation of the DMN and reduced activation of task-relevant regions. We investigated whether middle-aged type 2 diabetic patients show these brain activity patterns during encoding and recognition tasks. Compared with control participants, we observed both reduced 1) activation of the dorsolateral prefrontal cortex during encoding and 2) deactivation of the DMN during recognition in type 2 diabetic patients, despite normal cognition. During recognition, activation in several task-relevant regions, including the dorsolateral prefrontal cortex and DMN regions, was positively correlated with HbA1c and insulin resistance, suggesting that these important markers of glucose metabolism impact the brain's response to a cognitive challenge. Plasma glucose ≥11 mmol/L was associated with impaired deactivation of the DMN, suggesting that acute hyperglycemia contributes to brain abnormalities. Since elderly type 2 diabetic patients often demonstrate cognitive impairments, it is possible that these task-induced brain activity patterns observed in middle age may signal impending cognitive decline.
Introduction
Patients with type 2 diabetes are at increased risk for dementia and cognitive decline. Neuroimaging is useful for determining structural and functional biomarkers that may predict future cognitive impairment, thereby elucidating the mechanisms involved in cognitive decline and informing strategies to target vulnerable brain regions.
Recent research has focused on the default mode network (DMN), a set of medial prefrontal and temporo-parietal regions that are most active at rest and deactivated during cognitive tasks. The DMN exhibits both reduced functional connectivity and impaired task-induced deactivation in Alzheimer disease (AD) and mild cognitive impairment (MCI). These changes have been observed before atrophy and cognitive decline and are concurrent with other signals that are known predictors of cognitive decline. The DMN also has high metabolic activity, making it susceptible to the effects of type 2 diabetes and hypo- or hyperglycemia. Patients with type 2 diabetes show impaired functional connectivity and abnormal glucose metabolism in the DMN, but no study has investigated whether they show reduced ability to suppress DMN activity during a cognitive task.
This study investigates brain activity patterns during encoding and recognition tasks using functional magnetic resonance imaging (fMRI) in middle-aged type 2 diabetic patients, focusing on the DMN. These regions, in particular the prefrontal cortex, are involved in both encoding and recognition. Since elderly patients with type 2 diabetes often demonstrate cognitive impairments, it is important to identify task-related functional alterations that may precede cognitive decline so that preventative therapies can be introduced in middle age.
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