Cognitive performance declines in older adults with type 1 diabetes: results from 32 years of follow-up in the DCCT and EDIC Study
Open accessAbstract
Background With improved treatment, individuals with type 1 diabetes are living longer but there is limited information on the effects of type 1 diabetes on cognitive ability as they become older adults. We followed up individuals with type 1 diabetes to identify independent risk factors for cognitive decline as people age.Methods 1051 participants with type 1 diabetes enrolled in the Diabetes Control and Complications Trial (DCCT) and its follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. Participants completed cognitive assessments at baseline (median age 27 years) and 2, 5, 18, and 32 years later (median age 59). HbA 1c levels, frequency of severe hypoglycaemia, non-glycemic risk factors such as elevated blood pressure, and microvascular and macrovascular complications were assessed repeatedly. We examined the effects of these on measures of memory and psychomotor and mental efficiency. These studies are registered with clinicaltrials.gov, NCT00360815 (DCCT) and NCT00360893 (EDIC).Findings Over 32 years of follow-up, we found substantive declines in memory and psychomotor and mental efficiency. Between 18 and 32 years of follow-up, the decline in psychomotor and mental efficiency was five times larger than the change from baseline to year 18. Independent of the other risk factors and comorbidities, exposure to higher HbA 1c levels, more episodes of severe hypoglycaemia, and elevated systolic blood pressure were associated with greater decrements in psychomotor and mental efficiency that was most notable by year 32 (p<0·0001). The combined effect of the presence of these three risk factors is the equivalent to an additional 9·4 years of age.Interpretation Cognitive function declines with ageing in type 1 diabetes. The association of glycaemia and blood pressure levels with cognitive decline suggests that better management might preserve cognitive function.Funding United States National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease.
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Cognitive impairment has a strong bidirectional association with hypoglycemia.
“Cognitive impairment has a strong bidirectional association with hypoglycemia, and recurrent severe hypoglycemic episodes were associated with a greater decline in psychomotor and mental efficiency after long-term follow-up of the DCCT/EDIC cohort (118).”
From 6. Glycemic Goals, Hypoglycemia, and Hyperglycemic Crises: Standards of Care in Diabetes-2026. (2026) · cites this paper as [118]
The Results report that severe hypoglycemia was associated with greater decline in psychomotor and mental efficiency over follow-up, with worsening performance as the number of events increased. The Results and Discussion address hypoglycemia followed by cognitive decline, but do not establish the reverse association—that cognitive impairment is associated with subsequent hypoglycemia—so they do not support the claim of bidirectionality. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSevere hypoglycemia has been linked to increased risk of dementia.
“Cognitive decline has been associated with increased risk of hypoglycemia, and conversely, severe hypoglycemia has been linked to increased risk of dementia (30)(31)(32).”
From 13. Older Adults: <i>Standards of Care in Diabetes—2024</i> (2024) · cites this paper as [32]
The Results report that severe hypoglycemia was associated with declining psychomotor and mental efficiency in adults with type 1 diabetes, and the Discussion links it to clinically significant cognitive impairment. The paper does not report an increased risk of dementia, which is the more specific outcome in the claim. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSevere hypoglycemia has been linked to increased risk of dementia.
“Cognitive decline has been associated with increased risk of hypoglycemia, and conversely, severe hypoglycemia has been linked to increased risk of dementia (37–39).”
From 13. Older Adults: Standards of Care in Diabetes—2026 (2026) · cites this paper as [39]
The Results and Discussion (page not provided) link severe hypoglycemia to declining psychomotor and mental efficiency and to clinically significant cognitive impairment in older adults with type 1 diabetes. They do not establish an increased risk of dementia, which is the more specific outcome in the claim. (LLM, conf=0.86)
Experimental — accuracy not yet measuredCognitive decline has been associated with increased risk of hypoglycemia.
“Cognitive decline has been associated with increased risk of hypoglycemia, and conversely, severe hypoglycemia has been linked to increased risk of dementia (37–39).”
From 13. Older Adults: Standards of Care in Diabetes—2026 (2026) · cites this paper as [39]
The Results (page not available) associate a history of severe hypoglycemia with subsequent decline in psychomotor and mental efficiency. That supports an association between hypoglycemia and cognitive decline, but not the claimed direction: the paper does not show that cognitive decline is associated with an increased risk of future hypoglycemia. (LLM, conf=0.82)
Experimental — accuracy not yet measuredOlder adults with type 1 diabetes are more prone to mild cognitive impairment associated with hypoglycemia, while hypoglycemia occurs more frequently in those with cognitive impairment.
“It appears that older adults with type 1 diabetes are more prone to mild cognitive impairment associated with hypoglycemia (110,111), while hypoglycemia occurs more frequently in those with cognitive impairment.”
From The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) (2021) · cites this paper as [110]
The Discussion (page unavailable) associates severe hypoglycemia with cognitive decline in older adults with type 1 diabetes and reports an increased risk of clinically significant impairment in related studies. It does not establish that this cohort was more prone to mild cognitive impairment: its reported rate of possible mild cognitive impairment was 5.5%, versus 6.7% in general-population studies. The citation appears immediately after the first clause, so the subsequent statement about hypoglycemia occurring more frequently in people with cognitive impairment is not judged here. (LLM, conf=0.82)
Experimental — accuracy not yet measured
Recurrent severe hypoglycemic episodes were associated with a greater decline in psychomotor and mental efficiency after long-term follow-up of the DCCT/EDIC cohort.
“Cognitive impairment has a strong bidirectional association with hypoglycemia, and recurrent severe hypoglycemic episodes were associated with a greater decline in psychomotor and mental efficiency after long-term follow-up of the DCCT/EDIC cohort (118).”
From 6. Glycemic Goals, Hypoglycemia, and Hyperglycemic Crises: Standards of Care in Diabetes-2026. (2026) · cites this paper as [118]
Independent of other risk factors and comorbidities, more episodes of severe hypoglycemia were associated with greater decrements in psychomotor and mental efficiency that were most notable after 32 years of follow-up.
“However, independent of other risk factors and comorbidities, more episodes of severe hypoglycemia were associated with greater decrements in psychomotor and mental efficiency that were most notable after 32 years of follow-up (110).”
Cognitive decline has been associated with increased risk of hypoglycemia.
“Cognitive decline has been associated with increased risk of hypoglycemia, and conversely, severe hypoglycemia has been linked to increased risk of dementia (30)(31)(32).”
From 13. Older Adults: <i>Standards of Care in Diabetes—2024</i> (2024) · cites this paper as [32]
The Results and Discussion associate a history of severe hypoglycemia with later cognitive decline in older adults with type 1 diabetes. They do not address whether cognitive decline increases the risk of hypoglycemia—the direction attributed to this source. Searches for cognitive decline as a hypoglycemia risk factor found no supporting passage. (LLM, conf=0.75)
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References 36 · Cited by 138
- Authors
- Jacobson, A. M., Ryan, C. M., Braffett, B. H., Gubitosi-Klug, R. A., Lorenzi, G. M., Luchsinger, J. A., Trapani, V. R., Bebu, I., Chaytor, N., Hitt, S. M., Farrell, K., & Lachin, J. M.
- Affiliations
- NYU Langone Health (US)
- University of Pittsburgh (US)
- George Washington University (US)
- University of California San Diego (US)
- Washington State University Spokane (US)
- University of Missouri (US)
- Rainbow Babies & Children's Hospital (US)
- Corresponding author
- Jacobson, Alan M
- Venue
- The Lancet Diabetes & Endocrinology
- Publisher
- Elsevier BV
- Published
- 2021-07
- Volume
- 9
- Issue
- 7
- Pages
- 436-445
- ISSN
- 2213-8587 (ISSN-L)
- PMC
- PMC8583716
- OpenAlex
- W3164205577
- Cited by
- 138
- References
- 36
- Citations by year
- 2026: 25 · 2025: 36 · 2024: 23 · 2023: 24 · 2022: 22 · 2021: 8
- FWCI
- 14.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 350 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- The Lancet Diabetes & Endocrinology (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Eli Lilly and Company
- Abbott Diabetes Care
- Insulet Corporation
- National Eye Institute
- BD
- Roche Diabetes Care
- National Institute of Neurological Disorders and Stroke (2006)
- National Institute of Diabetes and Digestive and Kidney Diseases (U01 DK094157, U01 DK094176)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- type 1 diabetes, cognitive decline, older adults, memory, psychomotor efficiency, mental efficiency, HbA1c, glycemic control, severe hypoglycemia, systolic blood pressure, diabetes complications, aging, Diabetes Control and Complications Trial
- MeSH terms
- Adolescent, Adult, Aged, Cognition, Diabetes Mellitus, Type 1, Female, Follow-Up Studies, Humans, Male, Middle Aged, Time Factors, Young Adult, Cognitive Dysfunction
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