CoChat
Sign Up
Cited by 115Dementia and Cognitive Impairment ResearchDiabetes Management and ResearchDiabetes Treatment and Management

Severe hypoglycaemia, mild cognitive impairment, dementia and brain volumes in older adults with type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) cohort study

Open access
Lee, Alexandra K., Rawlings, Andreea M., Lee, Clare J., Gross, Alden L., Huang, Elbert S., Sharrett, A. Richey, Coresh, Josef, Selvin, Elizabeth·2018·Diabetologia
DOI 10.1007/s00125-018-4668-1PMC PMC6152822
Open this paper in CoChat — free accountOpen PDF

Abstract

Aims/hypothesis We aimed to evaluate the link between severe hypoglycaemia and domain-specific cognitive decline, smaller brain volumes and dementia in adults with type 2 diabetes, which so far has been relatively poorly characterised. Methods We included participants with diagnosed diabetes from the community-based Atherosclerosis Risk in Communities (ARIC) study. At the participants' fifth study visit (2011-2013), we examined the cross-sectional associations of severe hypoglycaemia with cognitive status, brain volumes and prior 15 year cognitive decline. We also conducted a prospective survival analysis of incident dementia from baseline, visit 4 (1996-1998), to 31 December 2013. Severe hypoglycaemia was identified, using ICD-9 codes, from hospitalisations, emergency department visits and ambulance records. Prior cognitive decline was defined as change in neuropsychological test scores from visit 4 (1996-1998) to visit 5 (2011-2013). At visit 5, a subset of participants underwent brain MRIs. Analyses were adjusted for demographics, APOE genotype, use of diabetes medication, duration of diabetes and glycaemic control. Results Among 2001 participants with diabetes at visit 5 (mean age 76 years), a history of severe hypoglycaemia (3.1% of participants) was associated with dementia (vs normal cognitive status): OR 2.34 (95% CI 1.04, 5.27). In the subset of participants who had undergone brain MRI (n = 580), hypoglycaemia was associated with smaller total brain volume (-0.308 SD, 95% CI -0.612, -0.004). Hypoglycaemia was nominally associated with a 15 year cognitive change (-0.14 SD, 95% CI -0.34, 0.06). In prospective analysis (n = 1263), hypoglycaemia was strongly associated with incident dementia (HR 2.54, 95% CI 1.78, 3.63). Conclusions/interpretation Our results demonstrate a strong link between severe hypoglycaemia and poor cognitive outcomes, suggesting a need for discussion of appropriate diabetes treatments for high-risk older adults.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1007/s00125-018-4668-1

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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 [31]

  • Severe 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 [31]

  • Severe 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 [38]

  • 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 (37–39).”

    From 13. Older Adults: Standards of Care in Diabetes—2026 (2026) · cites this paper as [38]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 29

  1. [3]Warren RE, Frier BM. Hypoglycemia and cognitive function. Diabetes, Obes Metab. 2005; 7: 493– 503. 16050942
  2. [4]Kang E, Jeon S, Choi S, Song C, Yu I. Diffusion MR imaging OF hypoglycemic Encephalopathy. Am J Neuroradiol. 2010; 31: 559– 564. 19875472 PMC7963995
  3. [5]Ma JH, Kim YJ, Yoo WJ MR imaging of hypoglycemic encephalopathy: lesion distribution and prognosis prediction by diffusion-weighted imaging. Neuroradiology. 2009; 51: 641– 649. 19533113
  4. [6]Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP Jr, Selby JV. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA. 2009; 301: 1565– 1572. 19366776 PMC2782622
  5. [7]Yaffe K, Falvey CM, Hamilton N Association between hypoglycemia and dementia in a biracial cohort of older adults with diabetes mellitus. JAMA Intern Med. 2013; 173: 1300– 1306. 23753199 PMC4041621
  6. [8]Lin CH, Sheu WHH. Hypoglycaemic episodes and risk of dementia in diabetes mellitus: 7-year follow-up study. J Intern Med. 2013; 273: 102– 110. 23003116
  7. [9]Bruce DG, Davis WA, Casey GP Severe hypoglycaemia and cognitive impairment in older patients with diabetes: the Fremantle Diabetes Study. Diabetologia. 2009; 52: 1808– 1815. 19575177
  8. [10]Feinkohl I, Aung PP, Keller M Severe hypoglycemia and cognitive decline in older people with type 2 diabetes: the Edinburgh type 2 diabetes study. Diabetes Care. 2014; 37: 507– 515. 24103900
  9. [13]Mattishent K, Loke YK. Bi-directional interaction between hypoglycaemia and cognitive impairment in elderly patients treated with glucose-lowering agents: a systematic review and meta-analysis. Diabetes Obes Metab. 2016; 18: 135– 141. 26446922
  10. [14]Punthakee Z, Miller ME, Launer LJ Poor cognitive function and risk of severe hypoglycemia in type 2 diabetes: post hoc epidemiologic analysis of the ACCORD trial. Diabetes Care. 2012; 35: 787– 793. 22374637 PMC3308284
  11. [15]De Galan BE, Zoungas S, Chalmers J Cognitive function and risks of cardiovascular disease and hypoglycaemia in patients with type 2 diabetes: the action in diabetes and vascular disease: preterax and diamicron modified release controlled evaluation (ADVANCE) trial. Diabetologia. 2009; 52: 2328– 2336. 19688336
  12. [16]Lee AK, Lee CJ, Huang ES, Sharrett AR. Risk factors for severe hypoglycemia in black and white adults with diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care. 2017; 40: 1661– 1667. 28928117 PMC5711330
  13. [17]Prinz N, Stingl J, Dapp A High rate of hypoglycemia in 6770 type 2 diabetes patients with comorbid dementia: a multicenter cohort study on 215,932 patients from the German/Austrian diabetes registry. Diabetes Res Clin Pract. 2015; 112: 73– 81. 26563590
  14. [18]Rawlings AM, Sharrett AR, Schneider ALC Diabetes in midlife and cognitive change over 20 years: a cohort study. Ann Intern Med. 2014; 161: 785– 793. 25437406 PMC4432464
  15. [19]Investigators ARIC. The Atherosclerosis Risk In Communities (ARIC) Study: design and objectives. Am J Epidemiol. 1989; 129: 687– 702. 2646917
  16. [20]Ginde AA, Blanc PG, Lieberman RM, Camargo CA. Validation of ICD-9-CM coding algorithm for improved identification of hypoglycemia visits. BMC Endocr Disord. 2008; 8: 4. 18380903 PMC2323001
  17. [21]Knopman DS, Gottesman RF, Sharrett AR Mild cognitive impairment and dementia prevalence: the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). Alzheimer’s Dement 2016; 2: 1– 11. PMC4772876 26949733
  18. [22]Gottesman RF, Albert MS, Alonso A Associations between midlife vascular risk factors and 25-year incident dementia in the Atherosclerosis Risk in Communities (ARIC) Cohort. JAMA Neurol. 2017; 74: 1246– 1254. 28783817 PMC5710244
  19. [23]Knopman DS, Griswold ME, Lirette ST Vascular Imaging abnormalities and cognition: mediation by cortical volume in nondemented individuals: Atherosclerosis risk in Communities-Neurocognitive Study. Stroke. 2015; 46: 433– 440. 25563642 PMC4308430
  20. [25]Gross AL, Power MC, Albert MS Application of latent variable methods to the study of cognitive decline when tests change over time. Epidemiology. 2015; 26: 878– 887. 26414855 PMC4819068
  21. [26]Georgakis MK, Dimitriou NG, Karalexi MA. Albuminuria in association with cognitive function and dementia: a systematic review and meta-analysis. J Am Geriatr Soc. 2017; 65: 1190– 1198. 28152169
  22. [27]Helmer C, Stengel B, Metzger M Chronic kidney disease, cognitive decline, and incident dementia: the 3C Study. Neurology. 2011; 77: 2043– 2051. 22116945
  23. [29]Auer RN, Siesjo BK. Hypoglycaemia: brain neurochemistry and neuropathology. Baillieres Clin Endocrinol Metab. 1993; 7: 611– 625. 8379907
  24. [30]Schneider ALC, Selvin E, Sharrett AR Diabetes, prediabetes, and brain volumes and subclinical cerebrovascular disease on MRI: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). Diabetes Care. 2017; 40: 1514– 1521. 28916531 PMC5652590
  25. [31]Biessels GJ, Strachan MWJ, Visseren FLJ, Kappelle LJ, Whitmer RA. Dementia and cognitive decline in type 2 diabetes and prediabetic stages: towards targeted interventions. Lancet Diabetes Endocrinol. 2014; 2: 246– 255. 24622755
  26. [32]Wilson RS, Schneider JA, Barnes LL The apolipoprotein E epsilon 4 allele and decline in different cognitive systems during a 6-year period. Arch Neurol. 2002; 59: 1154– 1160. 12117364
  27. [33]Cryer PE. Hypoglycemia, functional brain failure, and brain death. J Clin Invest. 2007; 117: 868– 870. 17404614 PMC1838950
  28. [35]Munshi MN, Slyne C, Segal AR, Saul N, Lyons C, Weinger K. Simplification of insulin regimen in older adults and risk of hypoglycemia. JAMA Intern Med. 2016; 176: 1023– 1025. 27273335
  29. [36]Vimalananda VG, DeSotto K, Chen T A quality improvement program to reduce potential overtreatment of diabetes among veterans at high risk of hypoglycemia. Diabetes Spectr. 2017; 30: 211– 216. 28848316 PMC5556587

Cited by

Sorted by citations

Authors
Lee, A. K., Rawlings, A. M., Lee, C. J., Gross, A. L., Huang, E. S., Sharrett, A. R., Coresh, J., & Selvin, E.
Affiliations
  • Johns Hopkins University (US)
  • University of Chicago (US)
Corresponding author
Selvin, Elizabeth
ORCID
Venue
Diabetologia
Publisher
Springer Science and Business Media LLC
Published
2018-06-30
Volume
61
Issue
9
Pages
1956-1965
ISSN
  • 0012-186X (ISSN-L)
  • 1432-0428
DOI
10.1007/s00125-018-4668-1
PMC
PMC6152822
OpenAlex
W2810882781
Cited by
115
References
4
Citations by year
2026: 6 · 2025: 16 · 2024: 12 · 2023: 14 · 2022: 23 · 2021: 14 · 2020: 12 · 2019: 16 · 2018: 1
FWCI
8.46
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Diabetologia (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5u01hl096899-08, 5u01hl096902-08)
  • Agency for Healthcare Research and Quality (R01HS018542)
  • National Heart, Lung, and Blood Institute (U01HL096814, U01-HL-096899, U01-HL-096902, U01HL096917, R01HL070825, T32HL007024, U01HL096812)
  • National Institute of Diabetes and Digestive and Kidney Diseases (K24DK105340, K24DK106414, R01DK089174, K23DK107921, P30DK092949)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
severe hypoglycemia, type 2 diabetes, dementia, mild cognitive impairment, cognitive decline, brain volume, older adults, incident dementia, APOE genotype, glycemic control, antidiabetic drugs, Atherosclerosis Risk in Communities Study, brain MRI, emergency department visits, neuropsychological assessment, APOE ε4
MeSH terms
Aged, Apolipoproteins E, Brain, Cognition, Cross-Sectional Studies, Dementia, Diabetes Mellitus, Type 2, Female, Genotype, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Organ Size, Cohort Studies, Cognitive Dysfunction

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 ›

Are you an author, or do you see a problem with this page? Request a review