Alexandra K Lee1,2, Andreea M Rawlings1,2, Clare J Lee3, Alden L Gross1,2,4, Elbert S Huang5, A Richey Sharrett1,2, Josef Coresh1,2, Elizabeth Selvin6,7. 1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. 2. Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, 2024 East Monument Street, Suite 2-600, Baltimore, MD, 21205, USA. 3. Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins School of Medicine, Baltimore, MD, USA. 4. Center on Aging and Health, Johns Hopkins University, Baltimore, MD, USA. 5. Section of Internal Medicine, University of Chicago Medicine, Chicago, IL, USA. 6. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. eselvin@jhu.edu. 7. Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, 2024 East Monument Street, Suite 2-600, Baltimore, MD, 21205, USA. eselvin@jhu.edu.
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.
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.
Authors: D G Bruce; W A Davis; G P Casey; R M Clarnette; S G A Brown; I G Jacobs; O P Almeida; T M E Davis Journal: Diabetologia Date: 2009-07-03 Impact factor: 10.122
Authors: Robert S Wilson; Julie A Schneider; Lisa L Barnes; Laurel A Beckett; Neelum T Aggarwal; Elizabeth J Cochran; Elizabeth Berry-Kravis; Julie Bach; Jacob H Fox; Denis A Evans; David A Bennett Journal: Arch Neurol Date: 2002-07
Authors: Kristine Yaffe; Cherie M Falvey; Nathan Hamilton; Tamara B Harris; Eleanor M Simonsick; Elsa S Strotmeyer; Ronald I Shorr; Andrea Metti; Ann V Schwartz Journal: JAMA Intern Med Date: 2013-07-22 Impact factor: 21.873
Authors: Geert Jan Biessels; Mark W J Strachan; Frank L J Visseren; L Jaap Kappelle; Rachel A Whitmer Journal: Lancet Diabetes Endocrinol Date: 2013-10-18 Impact factor: 32.069
Authors: Zubin Punthakee; Michael E Miller; Lenore J Launer; Jeff D Williamson; Ronald M Lazar; Tali Cukierman-Yaffee; Elizabeth R Seaquist; Faramarz Ismail-Beigi; Mark D Sullivan; Laura C Lovato; Richard M Bergenstal; Hertzel C Gerstein Journal: Diabetes Care Date: 2012-02-28 Impact factor: 19.112
Authors: Andrea L C Schneider; Elizabeth Selvin; A Richey Sharrett; Michael Griswold; Josef Coresh; Clifford R Jack; David Knopman; Thomas Mosley; Rebecca F Gottesman Journal: Diabetes Care Date: 2017-09-15 Impact factor: 19.112
Authors: Insa Feinkohl; Phyu Phyu Aung; Marketa Keller; Christine M Robertson; Joanne R Morling; Stela McLachlan; Ian J Deary; Brian M Frier; Mark W J Strachan; Jackie F Price Journal: Diabetes Care Date: 2013-10-08 Impact factor: 19.112
Authors: Andreea M Rawlings; A Richey Sharrett; Marilyn S Albert; Josef Coresh; B Gwen Windham; Melinda C Power; David S Knopman; Keenan Walker; Sheila Burgard; Thomas H Mosley; Rebecca F Gottesman; Elizabeth Selvin Journal: Diabetes Care Date: 2019-05-21 Impact factor: 19.112
Authors: Boris Draznin; Vanita R Aroda; George Bakris; Gretchen Benson; Florence M Brown; RaShaye Freeman; Jennifer Green; Elbert Huang; Diana Isaacs; Scott Kahan; Jose Leon; Sarah K Lyons; Anne L Peters; Priya Prahalad; Jane E B Reusch; Deborah Young-Hyman Journal: Diabetes Care Date: 2022-01-01 Impact factor: 19.112
Authors: Aniqa B Alam; Pamela L Lutsey; Lin Y Chen; Richard F MacLehose; Iris Y Shao; Alvaro Alonso Journal: Am J Cardiol Date: 2022-04-23 Impact factor: 3.133
Authors: Galit Weinstein; Kendra L Davis-Plourde; Sarah Conner; Jayandra J Himali; Alexa S Beiser; Anne Lee; Andreea M Rawlings; Sanaz Sedaghat; Jie Ding; Erin Moshier; Cornelia M van Duijn; Michal S Beeri; Elizabeth Selvin; M Arfan Ikram; Lenore J Launer; Mary N Haan; Sudha Seshadri Journal: PLoS One Date: 2019-02-15 Impact factor: 3.240