Effects of intensive glucose lowering on brain structure and function in people with type 2 diabetes (ACCORD MIND): a randomised open-label substudy
Open accessAbstract
Background People with type 2 diabetes are at risk of cognitive impairment and brain atrophy. We aimed to compare the effects on cognitive function and brain volume of intensive versus standard glycaemic control.Methods The Memory in Diabetes (MIND) study was done in 52 clinical sites in North America as part of Action to Control Cardiovascular Risk in Diabetes (ACCORD), a double two-by-two factorial parallel group randomised trial. Participants (aged 55-80 years) with type 2 diabetes, high glycated haemoglobin A(1c) (HbA(1c)) concentrations (>7·5%; >58 mmol/mol), and a high risk of cardiovascular events were randomly assigned to receive intensive glycaemic control targeting HbA(1c) to less than 6·0% (42 mmol/mol) or a standard strategy targeting HbA(1c) to 7·0-7·9% (53-63 mmol/mol). Randomisation was via a centralised web-based system and treatment allocation was not masked from clinic staff or participants. We assessed our cognitive primary outcome, the Digit Symbol Substitution Test (DSST) score, at baseline and at 20 and 40 months. We assessed total brain volume (TBV), our primary brain structure outcome, with MRI at baseline and 40 months in a subset of participants. We included all participants with follow-up data in our primary analyses. In February, 2008, raised mortality risk led to the end of the intensive treatment and transition of those participants to standard treatment. We tested our cognitive function hypotheses with a mixed-effects model that incorporated information from both the 20 and 40 month outcome measures. We tested our MRI hypotheses with an ANCOVA model that included intracranial volume and factors used to stratify randomisation. This study is registered with ClinicalTrials.gov, number NCT00182910.Findings We consecutively enrolled 2977 patients (mean age 62·5 years; SD 5·8) who had been randomly assigned to treatment groups in the ACCORD study. Our primary cognitive analysis was of patients with a 20-month or 40-month DSST score: 1378 assigned to receive intensive treatment and 1416 assigned to receive standard treatment. Of the 614 patients with a baseline MRI, we included 230 assigned to receive intensive treatment and 273 assigned to receive standard treatment in our primary MRI analysis at 40 months. There was no significant treatment difference in mean 40-month DSST score (difference in mean 0·32, 95% CI -0·28 to 0·91; p=0·2997). The intensive-treatment group had a greater mean TBV than the standard-treatment group (4·62, 2·0 to 7·3; p=0·0007).Interpretation Although significant differences in TBV favoured the intensive treatment, cognitive outcomes were not different. Combined with the non-significant effects on other ACCORD outcomes, and increased mortality in participants in the intensive treatment group, our findings do not support the use of intensive therapy to reduce the adverse effects of diabetes on the brain in patients with similar characteristics to those of our participants.Funding US National Institute on Aging and US National Heart, Lung, and Blood Institute.
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Studies on diabetes prevention or intensive glycemic and blood pressure management have not demonstrated a reduction in cognitive decline.
“However, studies on diabetes prevention or intensive glycemic and blood pressure management have not demonstrated a reduction in cognitive decline (20,21).”
From 13. Older Adults: Standards of Care in Diabetes—2025 (2025) · cites this paper as [20]
The Discussion (page not provided) reports no cognitive benefit from intensive versus standard glycemic treatment in participants with long-standing type 2 diabetes. The cited study does not establish the sentence’s broader claims about diabetes prevention or intensive blood-pressure management; its Introduction says it did not test early intervention. (LLM, conf=0.87)
Experimental — accuracy not yet measuredStudies on diabetes prevention or intensive glycemic and blood pressure management have not demonstrated a reduction in cognitive decline.
“However, studies on diabetes prevention or intensive glycemic and blood pressure management have not demonstrated a reduction in cognitive decline (25,26).”
From 13. Older Adults: Standards of Care in Diabetes—2026 (2026) · cites this paper as [25]
The Discussion reports no cognitive benefit from intensive versus standard glycemic treatment in older people with long-standing type 2 diabetes. The paper does not establish the claim about diabetes-prevention studies or intensive blood-pressure management; its Introduction says no clinical trials had tested early intervention on brain outcomes in this population. No page numbers were available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredStudies examining the effects of diabetes prevention or intensive glycemic and blood pressure management to achieve specific goals have not demonstrated a reduction in brain function decline.
“However, studies examining the effects of diabetes prevention or intensive glycemic and blood pressure management to achieve specific goals have not demonstrated a reduction in brain function decline (18,19).”
From 13. Older Adults: <i>Standards of Care in Diabetes—2024</i> (2024) · cites this paper as [18]
In the ACCORD trial, neither intensive glycemic control nor blood pressure control to a target systolic <120 mmHg was shown to prevent decline in brain function.
“In this trial, neither intensive glycemic control nor blood pressure control to a target systolic < 120 mmHg was shown to prevent decline in brain function61.”
From Diabetes in Older Adults: A Consensus Report (2012) · cites this paper as [61]
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Self-citation
- Authors
- Launer, L. J., Miller, M. E., Williamson, J. D., Lazar, R. M., Gerstein, H. C., Murray, A. M., Sullivan, M., Horowitz, K. R., Ding, J., Marcovina, S., Lovato, L. C., Lovato, J., Margolis, K. L., O'Connor, P., Lipkin, E. W., Hirsch, J., Coker, L., Maldjian, J., Sunshine, J. L., Truwit, C., Davatzikos, C., & Bryan, R. N.
- Affiliations
- National Institutes of Health (US)
- Wake Forest University Health Sciences (US)
- Population Health Research Institute (CA)
- Hennepin County Medical Center (US)
- University of Washington (US)
- Case Western Reserve University (US)
- Regions Hospital (US)
- Wake Forest University (US)
- Atrium Health Wake Forest Baptist (US)
- University of Pennsylvania Health System (US)
- Corresponding author
- Launer, Lenore J
- ORCID
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 10
- Issue
- 11
- Pages
- 969-977
- ISSN
- 1474-4422 (ISSN-L)
- PMC
- PMC3333485
- OpenAlex
- W2002257186
- Cited by
- 574
- References
- 39
- Citations by year
- 2026: 26 · 2025: 33 · 2024: 39 · 2023: 24 · 2022: 33 · 2021: 37 · 2020: 37 · 2019: 39 · 2018: 38 · 2017: 43 · 2016: 50 · 2015: 49 · 2014: 60 · 2013: 26 · 2012: 31
- FWCI
- 26.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging
- National Heart, Lung, and Blood Institute (AG-0002, N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- type 2 diabetes, tight glycemic control, cognitive function, brain volume, brain atrophy, HbA1c, Digit Symbol Substitution Test, magnetic resonance imaging, cognitive impairment, older adults, cardiovascular risk, treatment discontinuation, intracranial volume
- MeSH terms
- Aged, Aged, 80 and over, Blood Glucose, Blood Pressure, Brain, Cognition, Diabetes Mellitus, Type 2, Female, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Male, Middle Aged, Neuropsychological Tests, Organ Size, Fenofibrate
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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