Diabetes, markers of brain pathology and cognitive function
The Age, Gene/Environment Susceptibility–Reykjavik Study
Corresponding Author
Chengxuan Qiu PhD
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD
Aging Research Center, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet–Stockholm University, Stockholm, Sweden
Address correspondence to Dr Launer, Laboratory of Epidemiology and Population Sciences, National Institute on Aging/NIH, 7201 Wisconsin Avenue, Bethesda, MD 20892, USA. E-mail: [email protected]Search for more papers by this authorSigurdur Sigurdsson MSc
Icelandic Heart Association, Kopavogur, Iceland
Search for more papers by this authorQian Zhang MSc
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD
Search for more papers by this authorMaria K. Jonsdottir PhD
Icelandic Heart Association, Kopavogur, Iceland
Faculty of Psychology, University of Iceland, Reykjavik, Iceland
Search for more papers by this authorOlafur Kjartansson MD
Icelandic Heart Association, Kopavogur, Iceland
Departments of Neurology and Radiology, Landspitali University Hospital, Reykjavik, Iceland
Search for more papers by this authorGudny Eiriksdottir MSc
Icelandic Heart Association, Kopavogur, Iceland
Search for more papers by this authorMelissa E. Garcia MPH
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD
Search for more papers by this authorTamara B. Harris MD
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD
Search for more papers by this authorMark A. van Buchem MD, PhD
Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
Search for more papers by this authorVilmundur Gudnason MD, PhD
Icelandic Heart Association, Kopavogur, Iceland
Faculty of Medicine, University of Iceland, Reykjavik, Iceland
Search for more papers by this authorLenore J. Launer PhD
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD
Search for more papers by this authorCorresponding Author
Chengxuan Qiu PhD
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD
Aging Research Center, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet–Stockholm University, Stockholm, Sweden
Address correspondence to Dr Launer, Laboratory of Epidemiology and Population Sciences, National Institute on Aging/NIH, 7201 Wisconsin Avenue, Bethesda, MD 20892, USA. E-mail: [email protected]Search for more papers by this authorSigurdur Sigurdsson MSc
Icelandic Heart Association, Kopavogur, Iceland
Search for more papers by this authorQian Zhang MSc
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD
Search for more papers by this authorMaria K. Jonsdottir PhD
Icelandic Heart Association, Kopavogur, Iceland
Faculty of Psychology, University of Iceland, Reykjavik, Iceland
Search for more papers by this authorOlafur Kjartansson MD
Icelandic Heart Association, Kopavogur, Iceland
Departments of Neurology and Radiology, Landspitali University Hospital, Reykjavik, Iceland
Search for more papers by this authorGudny Eiriksdottir MSc
Icelandic Heart Association, Kopavogur, Iceland
Search for more papers by this authorMelissa E. Garcia MPH
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD
Search for more papers by this authorTamara B. Harris MD
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD
Search for more papers by this authorMark A. van Buchem MD, PhD
Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
Search for more papers by this authorVilmundur Gudnason MD, PhD
Icelandic Heart Association, Kopavogur, Iceland
Faculty of Medicine, University of Iceland, Reykjavik, Iceland
Search for more papers by this authorLenore J. Launer PhD
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD
Search for more papers by this authorAbstract
Objective
We investigated whether, and the extent to which, vascular and degenerative lesions in the brain mediate the association of diabetes with poor cognitive performance.
Methods
This cross-sectional study included 4,206 participants (age > 65 years; 57.8% women) of the Age, Gene/Environment Susceptibility–Reykjavik Study. Data were collected through interview, clinical examination, psychological testing, and laboratory tests. The composite scores on memory, information-processing speed, and executive function were derived from a cognitive test battery. Markers of cerebral macrovascular (cortical infarcts), microvascular (subcortical infarcts, cerebral microbleeds, and higher white matter lesion volume), and neurodegenerative (lower gray matter, normal white matter, and total brain tissue volumes) processes were assessed on magnetic resonance images. Mediation models were employed to test the mediating effect of brain lesions on the association of diabetes with cognitive performance controlling for potential confounders.
Results
There were 462 (11.0%) persons with diabetes. Diabetes was significantly associated with lower scores on processing speed and executive function, but not with memory function. Diabetes was significantly associated with all markers of brain pathology. All of these markers were significantly associated with lower scores on memory, processing speed, and executive function. Formal mediation tests suggested that markers of cerebrovascular and degenerative pathology significantly mediated the associations of diabetes with processing speed and executive function.
Interpretation
Diabetes is associated with poor performance on cognitive tests of information-processing speed and executive function. The association is largely mediated by markers of both neurodegeneration and cerebrovascular disease. Older people with diabetes should be monitored for cognitive problems and brain lesions. Ann Neurol 2014;75:138–146
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