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Diabetes is associated with cerebrovascular but not Alzheimer's disease neuropathology
Open accessAbstract
Introduction: The relationship of diabetes to specific neuropathologic causes of dementia is incompletely understood. Methods: We used logistic regression to evaluate the association between diabetes and infarcts, Braak neurofibrillary tangle stage, and neuritic plaque score in 2365 autopsied persons. In a subset of >1300 persons with available cognitive data, we examined the association between diabetes and cognition using Poisson regression. Results: Diabetes increased odds of brain infarcts (odds ratio [OR] = 1.57, P < .0001), specifically lacunes (OR = 1.71, P < .0001), but not Alzheimer's disease neuropathology. Diabetes plus infarcts was associated with lower cognitive scores at end of life than infarcts or diabetes alone, and diabetes plus high level of Alzheimer's neuropathologic changes was associated with lower mini‐mental state examination scores than the pathology alone. Discussion: This study supports the conclusions that diabetes increases the risk of cerebrovascular but not Alzheimer's disease pathology, and at least some of diabetes' relationship to cognitive impairment may be modified by neuropathology.
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“In contrast, in clinical-autopsy studies, diabetes was associated with cognitive impairment (and the clinical diagnosis of probable AD); however, the pathologic basis for this association was vascular brain injury and not Aβ plaques and neurofibrillary degeneration [50,216].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [216]
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Self-citationTalbot, K., Wang, H.-Y., Kazi, H., Han, L.-Y., Bakshi, K. P., Stucky, A., Fuino, R. L., Kawaguchi, K. R., Samoyedny, A. J., Wilson, R. S., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59903 · Cited by 1,871
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“Epidemiological, clinical, and neuroimaging studies have also identified increased risk of cerebrovascular disease (CVD) linked to diabetes [19-21].”
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NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.018 · Cited by 10,537
“In contrast, in clinical-autopsy studies, diabetes was associated with cognitive impairment (and the clinical diagnosis of probable AD); however, the pathologic basis for this association was vascular brain injury and not Aβ plaques and neurofibrillary degeneration [50,216].”
Self-citationBrain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums
Arnold, S. E., Arvanitakis, Z., Macauley-Rambach, S. L., Koenig, A. M., Wang, H.-Y., Ahima, R. S., Craft, S., Gandy, S., Buettner, C., Stoeckel, L. E., et al. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.185 · Cited by 1,597
Self-citationCognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications
Biessels, G. J., & Despa, F. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0048-7 · Cited by 1,454
The burden and risks of emerging complications of diabetes mellitus
Tomic, D., Shaw, J. E., & Magliano, D. J. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00690-7 · Cited by 1,377
Post-Stroke Cognitive Impairment and Dementia
Rost, N. S., Brodtmann, A. G., Pase, M. P., van Veluw, S. J., Biffi, A., Duering, M., Hinman, J. D., & Dichgans, M. (2022) · Circulation Research · doi:10.1161/circresaha.122.319951 · Cited by 864
Metadata
- Authors
- Abner, E. L., Nelson, P. T., Kryscio, R. J., Schmitt, F. A., Fardo, D. W., Woltjer, R. L., Cairns, N. J., Yu, L., Dodge, H. H., Xiong, C., Masaki, K., Tyas, S. L., Bennett, D. A., Schneider, J. A., & Arvanitakis, Z.
- Affiliations
- University of Kentucky (US)
- Oregon Health & Science University (US)
- Washington University in St. Louis (US)
- Rush University Medical Center (US)
- University of Hawaiʻi at Mānoa (US)
- University of Waterloo (CA)
- Corresponding author
- Abner, Erin L.
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2016-01-23
- Volume
- 12
- Issue
- 8
- Pages
- 882-889
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC4958598
- OpenAlex
- W2287966587
- Cited by
- 233
- References
- 53
- Citations by year
- 2026: 9 · 2025: 20 · 2024: 20 · 2023: 18 · 2022: 32 · 2021: 20 · 2020: 25 · 2019: 29 · 2018: 19 · 2017: 29 · 2016: 12
- FWCI
- 26.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UKnowledge (University of Kentucky) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute on Aging (R01‐AG038651, P30‐AG10161, R01‐AG15819, R01‐AG17917, P30‐AG028383, P50‐AG005681, P30‐AG008017, N01‐AG‐4‐2149, U01‐AG019349, U01‐AG017155)
- National Heart, Lung, and Blood Institute (N01‐HC‐05102)
- U.S. Department of Veterans Affairs
- National Institute of Neurological Disorders and Stroke (R01‐NS084965)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- diabetes mellitus, cerebrovascular disease
- MeSH terms
- Aged, 80 and over, Alzheimer Disease, Animals, Autopsy, Brain, Cognition Disorders, Diabetes Mellitus, Female, Humans, Male, Mental Status Schedule, Neuropsychological Tests, Cohort Studies, Logistic Models, Neurofibrillary Tangles, Brain Infarction, Diabetes Complications
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