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Association of type 2 diabetes with brain atrophy and cognitive impairment
Open accessAbstract
OBJECTIVE: We investigated the associations of diabetes and hypertension with imaging biomarkers (markers of neuronal injury and ischemic damage) and with cognition in a population-based cohort without dementia. METHODS: Participants (n = 1,437, median age 80 years) were evaluated by a nurse and physician and underwent neuropsychological testing. A diagnosis of cognitively normal, mild cognitive impairment (MCI), or dementia was made by an expert panel. Participants underwent MRI to determine cortical and subcortical infarctions, white matter hyperintensity (WMH) volume, hippocampal volume (HV), and whole brain volume (WBV). The medical records were reviewed for diabetes and hypertension in midlife or later. RESULTS: Midlife diabetes was associated with subcortical infarctions (odds ratio, 1.85 [95% confidence interval, 1.09-3.15]; p = 0.02), reduced HV (-4% [-7 to -1.0]; p = 0.01), reduced WBV (-2.9% [-4.1 to -1.6]), and prevalent MCI (odds ratio, 2.08; p = 0.01). The association between diabetes and MCI persisted with adjustment for infarctions and WMH volume but was attenuated after adjustment for WBV (1.60 [0.87-2.95]; p = 0.13) and HV (1.82 [1.00-3.32]; p = 0.05). Midlife hypertension was associated with infarctions and WMH volume and was marginally associated with reduced performance in executive function. Effects of late-life onset of diabetes and hypertension were few. CONCLUSIONS: Midlife onset of diabetes may affect late-life cognition through loss of brain volume. Midlife hypertension may affect executive function through ischemic pathology. Late-life onset of these conditions had fewer effects on brain pathology and cognition.
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“Older adults with diabetes are at higher risk of cognitive decline and institutionalization (12,13).”
From 13. Older Adults: Standards of Care in Diabetes—2024 (2024) · cites this paper as [13]
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“Older adults with diabetes are at higher risk of cognitive decline and institutionalization (13,14).”
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“Older adults with diabetes are at higher risk of cognitive decline and institutionalization than older adults without diabetes (17–19).”
From 13. Older Adults: Standards of Care in Diabetes—2026 (2026) · cites this paper as [18]
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Cited by
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Defeating Alzheimer's disease and other dementias: a priority for European science and society
Winblad, B., Amouyel, P., Andrieu, S., Ballard, C., Brayne, C., Brodaty, H., Cedazo-Minguez, A., Dubois, B., Edvardsson, D., Feldman, H., et al. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)00062-4 · Cited by 1,676
13. Older Adults: Standards of Medical Care in Diabetes—2022
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13. Older Adults: Standards of Care in Diabetes—2025
American Diabetes Association Professional Practice Committee, ElSayed, N. A., McCoy, R. G., Aleppo, G., Balapattabi, K., Beverly, E. A., Briggs Early, K., Bruemmer, D., Echouffo-Tcheugui, J. B., Ekhlaspour, L., et al. (2025) · Diabetes Care · doi:10.2337/dc25-s013 · Cited by 209
13. Older Adults: Standards of Care in Diabetes—2024
American Diabetes Association Professional Practice Committee, ElSayed, N. A., Aleppo, G., Bannuru, R. R., Bruemmer, D., Collins, B. S., Ekhlaspour, L., Hilliard, M. E., Johnson, E. L., Khunti, K., et al. (2024) · Diabetes Care · doi:10.2337/dc24-s013 · Cited by 161
Metadata
- Authors
- Roberts, R. O., Knopman, D. S., Przybelski, S. A., Mielke, M. M., Kantarci, K., Preboske, G. M., Senjem, M. L., Pankratz, V. S., Geda, Y. E., Boeve, B. F., Ivnik, R. J., Rocca, W. A., Petersen, R. C., & Jack, C. R.
- Affiliations
- Mayo Clinic in Arizona (US)
- ORCID
- Venue
- Neurology
- Published
- 2014-04
- Volume
- 82
- Issue
- 13
- Pages
- 1132-1141
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3966799
- OpenAlex
- W1997366085
- Cited by
- 211
- References
- 7
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 19 · 2023: 10 · 2022: 19 · 2021: 16 · 2020: 27 · 2019: 18 · 2018: 13 · 2017: 16 · 2016: 25 · 2015: 23 · 2014: 10
- FWCI
- 18.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5u01ag024904-10)
- U.S. Public Health Service (U01-96917)
- National Institute on Aging (U01-AG-024904, R01AG034676, R01AG029550, P50AG044170, R01AG040042, U01AG006786, R01AG011378, R01AG032306, K01AG028573, R01AG041851, P50AG016574)
- National Heart, Lung, and Blood Institute (U01HL096917)
- National Institute of Mental Health (K01-MH68351, K01MH068351)
- National Cancer Institute (DHHS/OS 90BC0009)
- National Institute of Neurological Disorders and Stroke (R21NS066147)
- National Center for Research Resources (RR-024150, UL1RR024150)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Clinical Neurology › Cerebrovascular and genetic disorders
- Keywords
- type 2 diabetes, hypertension, brain atrophy, cognitive impairment, mild cognitive impairment, white matter hyperintensities, subcortical infarcts, hippocampal volume, total brain volume, executive function
- MeSH terms
- Aged, Aged, 80 and over, Atrophy, Brain, Cognition Disorders, Diabetes Mellitus, Type 2, Female, Humans, Hypertension, Male, Population Surveillance, Prospective Studies, Risk Factors, Cohort Studies
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- CoChat. (2026). Citation check: Association of type 2 diabetes with brain atrophy and cognitive impairment. https://app.cochat.ai/papers/10.1212/wnl.0000000000000269
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- Roberts, R. O., Knopman, D. S., Przybelski, S. A., Mielke, M. M., Kantarci, K., Preboske, G. M., Senjem, M. L., Pankratz, V. S., Geda, Y. E., Boeve, B. F., Ivnik, R. J., Rocca, W. A., Petersen, R. C., & Jack, C. R. (2014). Association of type 2 diabetes with brain atrophy and cognitive impairment. Neurology. https://doi.org/10.1212/wnl.0000000000000269
