Abstract
How acute hyperglycaemia affects memory functions and functional brain responses in individuals with and without type 2 diabetes is unclear. Our aim was to study the association between acute hyperglycaemia and working, semantic, and episodic memory in participants with type 2 diabetes compared to a sex- and age-matched control group. We also assessed the effect of hyperglycaemia on working memory–related brain activity. A total of 36 participants with type 2 diabetes and 34 controls (mean age, 66 years) underwent hyperglycaemic clamp or placebo clamp in a blinded and randomised order. Working, episodic, and semantic memory were tested. Overall, the control group had higher working memory (mean z-score 33.15 ± 0.45) than the group with type 2 diabetes (mean z-score 31.8 ± 0.44, p = 0.042) considering both the placebo and hyperglycaemic clamps. Acute hyperglycaemia did not influence episodic, semantic, or working memory performance in either group. Twenty-two of the participants (10 cases, 12 controls, mean age 69 years) were randomly invited to undergo the same clamp procedures to challenge working memory, using 1-, 2-, and 3-back, while monitoring brain activity by blood oxygen level–dependent functional magnetic resonance imaging (fMRI). The participants with type 2 diabetes had reduced working memory during the 1- and 2-back tests. fMRI during placebo clamp revealed increased BOLD signal in the left lateral frontal cortex and the anterior cingulate cortex as a function of working memory load in both groups (3>2>1). During hyperglycaemia, controls showed a similar load-dependent fMRI response, whereas the type 2 diabetes group showed decreased BOLD response from 2- to 3-back. These results suggest that impaired glucose metabolism in the brain affects working memory, possibly by reducing activity in important frontal brain areas in persons with type 2 diabetes.
Highlights
With an aging population, Western societies will likely experience an increased prevalence of type 2 diabetes [1], which will increase the burden of associated complications, such as cardiovascular disease, retinopathy, nephropathy, and neuropathy
We found that fasting glucose, but not 2-hour glucose or insulin resistance, was associated with episodic memory but found no association with semantic or working memory
In the functional magnetic resonance imaging (fMRI) study, we evaluated the impact of hyperglycaemia on working memory performance
Summary
Western societies will likely experience an increased prevalence of type 2 diabetes [1], which will increase the burden of associated complications, such as cardiovascular disease, retinopathy, nephropathy, and neuropathy. We previously studied the effect of fasting glucose, 2-hour glucose, and insulin resistance in a non-diabetic population in which episodic, semantic, and working memory were assessed [7]. We found that fasting glucose, but not 2-hour glucose or insulin resistance, was associated with episodic memory but found no association with semantic or working memory. Fasting glucose has been speculated to affect the hippocampus, the area in the brain most important to episodic memory. Our studies implied that episodic or working memory, but not semantic memory, is afflicted at different stages of poor glucose regulation. Most of our understating of the association between glucose regulation and memory function is based on observational studies, but the mechanism underlying the link between memory impairment and changes in glucose control remains largely unknown
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