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.
Increased Glucose Levels Are Associated With Episodic Memory in Nondiabetic Women
Olov Rolandsson 1 ,
Anna Backeström 1 ,
Sture Eriksson 2 ,
Göran Hallmans 3 and
Lars-Göran Nilsson 4
1 Department of ...Public Health and Clinical Medicine, Family Medicine, Umeå University, Umeå, Sweden
2 Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeå University, Umeå, Sweden
3 Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden
4 Department of Psychology, Stockholm University, Stockholm, Sweden
Address correspondence and reprint requests to Dr. Olov Rolandsson, Family Medicine, Department of Public Health and Clinical
Medicine, NUS, S-901 85 Umeå, Sweden. E-mail: olov.rolandsson{at}fammed.umu.se
Abstract
OBJECTIVE —Patients with type 2 diabetes have an increased risk of a reduction in cognitive function. We investigated the hypothesis
that plasma glucose is associated with a reduction in episodic and/or semantic memory already in nondiabetic subjects.
RESEARCH DESIGN AND METHODS —We linked two large population-based datasets in Sweden: the Betula study, in which a random sample from the population aged
35–85 years was investigated for cognitive function, including episodic and semantic memory; and the Västerbotten Intervention
Program, a health survey with subjects aged 40, 50, and 60 years, that includes measuring of fasting and 2-h plasma glucose,
along with other risk factors for diabetes and cardiovascular disease. We identified 411 (179 men and 232 women, mean age
50.6 ± 8.0 years) nondiabetic subjects, free from dementia, who had participated in the two surveys within 6 months.
RESULTS —Women had better episodic (score 7.37 ± 1.42) and semantic memory (score 16.05 ± 2.76) than men (score 6.59 ± 1.29 and 15.15
± 2.92, respectively, P < 0.001 for both). In an adjusted multivariate model, fasting plasma glucose (fPG) and 2-h plasma glucose (2hPG) were significantly
negatively associated with episodic memory (fPG: B −0.198, SE 0.068, β −0.209, P = 0.004; and 2hPG: B −0.061, SE 0.031, β −0.148, P = 0.048, respectively) in women but not in men. The association was not found in relation to semantic memory.
CONCLUSIONS —We conclude that an increase in plasma glucose is associated with impairment in episodic memory in women. This could be explained
by a negative effect on the hippocampus caused by raised plasma glucose levels.
2hPG, 2-hour plasma glucose
CES-D, the Center for Epidemiologic Studies Depression Scale
fPG, fasting plasma glucose
IFG, impaired fasting glucose
IGT, impaired glucose tolerance
MMSE, Mini Mental State Examination
OGTT, oral glucose tolerance test
VIF, variance inflation factor
VIP, Västerbotten Intervention Program
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 31 October 2007. DOI: 10.2337/db07-1215.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted October 25, 2007.
Received August 30, 2007.
DIABETES
Elevated concentrations of plasma glucose appear to play a role in memory impairment, and it has been suggested that insulin might also have a negative effect on cognitive function. Our aim was to ...study whether glucose, insulin or insulin resistance are associated with episodic or semantic memory in a non-diabetic and non-demented population.
We linked and matched two population-based data sets identifying 291 participants (127 men and 164 women, mean age of 50.7 ± 8.0 years). Episodic and semantic memory functions were tested, and fasting plasma insulin, fasting plasma glucose, and 2-hour glucose were analysed along with other potential influencing factors on memory function. Since men and women display different results on memory functions they were analysed separately. Insulin resistance was calculated using the HOMA-IR method.
A higher fasting plasma glucose concentration was associated with lower episodic memory in women (r = -0.08, 95% CI -0.14; -0.01), but not in men. Plasma insulin levels and insulin resistance were not associated with episodic or semantic memory in women or in men after adjustments for age, fasting glucose, 2-hour glucose, BMI, education, smoking, cardiovascular disease, hypertension, cholesterol, and physical activity.
This indicates that fasting glucose but not insulin, might have impact on episodic memory in middle-aged women.
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