Presence of the APOE ε4 allele modifies the relationship between type 2 diabetes and cognitive performance: the Maine–Syracuse Study
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Aims/hypothesis The primary aim of this study was to determine whether the presence of one or more APOE epsilon4 alleles modifies the association between diabetes (defined by glucose > or =7 mmol/l or treatment) and cognitive function.Methods Diabetic status and APOE genotype interactions were assessed cross-sectionally for 826 community-dwelling, stroke-free, non-demented individuals (526 non-diabetic non-APOE epsilon4 carriers, 174 non-diabetic APOE epsilon4 carriers, 87 diabetic APOE epsilon4 non-carriers, 39 diabetic APOE epsilon4 carriers) ranging in age from 50 to 98 years. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), the similarities subtest from the Wechsler Adult Intelligence Scale, and four composite scores derived from 17 additional neuropsychological tests. Multiple linear regression analyses were employed to relate diabetes and APOE genotype to cognitive performance and to examine the interaction between these two risk factors as they relate to cognitive performance. Multiple cardiovascular disease risk factors were statistically controlled.Results With adjustment for age, education, sex, race/ethnicity and APOE genotype, performance level was lower for the diabetic than for the non-diabetic group for the MMSE, the similarities subtest and each of the cognitive composites with the exception of the verbal memory composite. Interactions (p < 0.05) between diabetes and APOE genotype were found for all but the visual-spatial memory/organisation composite. The negative association between diabetes and cognitive performance was of a higher magnitude for individuals who carry one or more APOE epsilon4 alleles. Results were similar with additional adjustment for cardiovascular disease and associated risk factors.Conclusions/interpretation The presence of one or more APOE epsilon4 alleles modifies the association between diabetes and cognitive function.
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Reduced cardiac output is associated with executive dysfunction (mainly sequencing and planning difficulties) and regional WMLs adjacent to subcortical nuclei.
“Specifically, reduced cardiac output has been associated with executive dysfunction (mainly sequencing and planning difficulties)381 and regional WMLs adjacent to the subcortical nuclei.382”
From Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association (2011) · cites this paper as [381]
The Discussion mentions white matter lesions in relation to diabetes, but does not link them to cardiac output or locate them adjacent to subcortical nuclei. Searches for reduced cardiac output and regional white matter lesions found no passage addressing that association. Citation 382 is attached to the white-matter-lesion part of the citing sentence. (LLM, conf=0.76)
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- Authors
- Dore, G. A., Elias, M. F., Robbins, M. A., Elias, P. K., & Nagy, Z.
- Affiliations
- University of Maine (US)
- University of Birmingham (GB)
- Corresponding author
- Dore, G. A.
- Venue
- Diabetologia
- Published
- 2009-08-20
- Volume
- 52
- Issue
- 12
- Pages
- 2551-2560
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2002408824
- Cited by
- 81
- References
- 46
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 2 · 2019: 6 · 2018: 4 · 2017: 4 · 2016: 6 · 2015: 4 · 2014: 8 · 2013: 10 · 2012: 6
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG-03055)
- National Heart, Lung, and Blood Institute (R01HL067358, R01HL081290, HL67358, HL81290)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- APOE ε4, type 2 diabetes, cognitive performance, gene-disease interaction, Alzheimer's disease risk, cognitive decline, older adults, cardiovascular risk factors, verbal memory, visuospatial memory
- MeSH terms
- Aged, Alleles, Cognition, Cognition Disorders, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Genotype, Humans, Life Style, Logic, Maine, Memory, Middle Aged, Neuropsychological Tests, New York, Psychological Tests, Reference Values, Regression Analysis, Verbal Learning, Visual Perception, Patient Selection, Apolipoprotein E4
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