Uncontrolled diabetes increases the risk of Alzheimer’s disease: a population-based cohort study
Open accessAbstract
Aims/hypothesis Diabetes has been related to Alzheimer's disease with inconsistent findings. We aimed to clarify the association of diabetes with different dementing disorders taking into account glycaemic control, and to explore the link between glucose dysregulation and neurodegeneration. Methods A dementia-free cohort (n = 1,248) aged >or=75 years was longitudinally examined to detect dementia, Alzheimer's disease and vascular dementia (VaD) cases (Diagnostic and Statistical Manual of Mental Disorders, revised third edition [DSM-III-R] criteria). The Alzheimer's disease diagnoses were subdivided into Alzheimer's disease with stroke and Alzheimer's disease without hypertension, heart disease and stroke. Diabetes was ascertained based on medical history, or hypoglycaemic medication use, or a random blood glucose level >or=11.0 mmol/l, which included undiagnosed diabetes when neither a history of diabetes nor hypoglycaemic drugs use was present. Uncontrolled diabetes was classified as a random blood glucose level >or=11.0 mmol/l in diabetic patients. Borderline diabetes was defined as a random blood glucose level of 7.8-11.0 mmol/l in diabetes-free individuals. Cox models were used to estimate HRs. Results During the 9 year follow-up, 420 individuals developed dementia, including 47 with VaD and 320 with Alzheimer's disease (of the 320 Alzheimer's disease cases, 78 had previous, temporally unrelated stroke, and 137 had no major vascular comorbidities). Overall diabetes was only related to VaD (HR 3.21, 95% CI 1.20-8.63). Undiagnosed diabetes led to an HR of 3.29 (95% CI 1.20-9.01) for Alzheimer's disease. Diabetic patients with random blood glucose levels <7.8 mmol/l showed no increased dementia risk. Uncontrolled and borderline diabetes were further associated with Alzheimer's disease without vascular comorbidities. Conclusions/interpretation Uncontrolled diabetes increases the risk of Alzheimer's disease and VaD. Our findings suggest a direct link between glucose dysregulation and neurodegeneration.
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People with diabetes have higher incidences of all-cause dementia, Alzheimer disease, and vascular dementia than people with normal glucose tolerance.
“People with diabetes have higher incidences of all-cause dementia, Alzheimer disease, and vascular dementia than people with normal glucose tolerance (14).”
From 13. Older Adults: <i>Standards of Care in Diabetes—2024</i> (2024) · cites this paper as [14]
The Results and Table 3 (page unavailable in our copy) compare participants with diabetes against a normal reference group and find an increased risk of vascular dementia for diabetes overall. Increased risks of all-cause dementia and Alzheimer’s disease appear for undiagnosed diabetes, not diabetes overall; the Abstract likewise states that overall diabetes was related only to vascular dementia. The claim omits that distinction. (LLM, conf=0.90)
Experimental — accuracy not yet measuredPeople with diabetes have higher incidences of all-cause dementia, Alzheimer disease, and vascular dementia than people without diabetes.
“People with diabetes have higher incidences of all-cause dementia, Alzheimer disease, and vascular dementia than people without diabetes (15).”
From 13. Older Adults: Standards of Care in Diabetes—2025 (2025) · cites this paper as [15]
The Results (page not provided) report increased vascular dementia risk for the overall diabetes group, but not increased risk of all-cause dementia or Alzheimer disease for that group. Increased risks for all three outcomes were reported for the subgroup with undiagnosed diabetes, so the citing sentence overgeneralizes the finding to all people with diabetes. (LLM, conf=0.90)
Experimental — accuracy not yet measuredPeople with diabetes have higher incidences of all-cause dementia, Alzheimer disease, and vascular dementia than people without diabetes.
“People with diabetes have higher incidences of all-cause dementia, Alzheimer disease, and vascular dementia than people without diabetes (20).”
From 13. Older Adults: Standards of Care in Diabetes—2026 (2026) · cites this paper as [20]
The Results report increased dementia, Alzheimer’s disease, and vascular dementia risk for people with undiagnosed diabetes, but not for diabetic patients with blood glucose below 7.8 mmol/l. The Abstract states that overall diabetes was related only to vascular dementia. The claim therefore overgeneralizes findings from a diabetes subgroup to all people with diabetes. (LLM, conf=0.90)
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- Authors
- Xu, W. L., von Strauss, E., Qiu, C. X., Winblad, B., & Fratiglioni, L.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Xu, W. L.
- Venue
- Diabetologia
- Published
- 2009-03-12
- Volume
- 52
- Issue
- 6
- Pages
- 1031-1039
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W1994735836
- Cited by
- 272
- References
- 4
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 20 · 2023: 12 · 2022: 15 · 2021: 13 · 2020: 18 · 2019: 20 · 2018: 13 · 2017: 17 · 2016: 19 · 2015: 11 · 2014: 15 · 2013: 21 · 2012: 20
- FWCI
- 11.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Association
- Vetenskapsrådet
- Stiftelsen Solstickan
- Swedish Brain Power
- Alzheimerfonden
- National Institute of Neurological Disorders and Stroke
- 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
- uncontrolled diabetes, Alzheimer's disease, vascular dementia, dementia risk, glucose dysregulation, glycemic control, random blood glucose, undiagnosed diabetes, prediabetes, stroke, neurodegeneration, older adults
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Blood Glucose, Diabetes Mellitus, Female, Humans, Male, Risk Factors, Dementia, Vascular, Cohort Studies, Proportional Hazards Models, Diabetes Complications
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